scholarly journals Quantifying Uncertainty and Robustness in a Biomathematical Model Based Patient-Specific Response Metric for Glioblastoma

2018 ◽  
Author(s):  
Andrea Hawkins-Daarud ◽  
Sandra K. Johnston ◽  
Kristin R. Swanson
Keyword(s):  
Synthetic Data ◽  
Magnetic Resonance Images ◽  
Patient Specific ◽  
Specific Response ◽  
Time To Progression ◽  
Interobserver Error ◽  
Standard Response ◽  
Pre Treatment ◽  
Tumor Kinetics ◽  
The Impact

AbstractGlioblastomas, lethal primary brain tumors, are known for their heterogeneity and invasiveness. A growing literature has been developed demonstrating the clinical relevance of a biomathematical model, the Proliferation-Invasion (PI) model, of glioblastoma growth. Of interest here is the development of a treatment response metric, Days Gained (DG). This metric is based on individual tumor kinetics estimated through segmented volumes of hyperintense regions on T1-weighted gadolinium enhanced (T1Gd) and T2-weighted magnetic resonance images (MRIs). This metric was shown to be prognostic of time to progression. Further, it was shown to be more prognostic of outcome than standard response metrics. While promising, the original paper did not account for uncertainty in the calculation of the DG metric leaving the robustness of this cutoff in question. We harness the Bayesian framework to consider the impact of two sources of uncertainty: 1) image acquisition and 2) interobserver error in image segmentation. We first utilize synthetic data to characterize what non-error variants are influencing the final uncertainty in the DG metric. We then consider the original patient cohort to investigate clinical patterns of uncertainty and to determine how robust this metric is for predicting time to progression and overall survival. Our results indicate that the key clinical variants are the time between pre-treatment images and the underlying tumor growth kinetics, matching our observations in the clinical cohort. Finally, we demonstrated that for this cohort there was a continuous range of cutoffs between 94 and 105 for which the prediction of the time to progression and was over 80% reliable. While further validation must be done, this work represents a key step in ascertaining the clinical utility of this metric.

scholarly journals Quantifying Uncertainty and Robustness in a Biomathematical Model–Based Patient-Specific Response Metric for Glioblastoma

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Andrea Hawkins-Daarud ◽  
Sandra K. Johnston ◽  
Kristin R. Swanson
Keyword(s):  
Synthetic Data ◽  
Magnetic Resonance Images ◽  
Patient Specific ◽  
Specific Response ◽  
Time To Progression ◽  
Interobserver Error ◽  
Standard Response ◽  
Clinical Variants ◽  
Tumor Kinetics ◽  
The Impact

Purpose Glioblastomas, lethal primary brain tumors, are known for their heterogeneity and invasiveness. A growing body of literature has been developed demonstrating the clinical relevance of a biomathematical model, the proliferation-invasion model, of glioblastoma growth. Of interest here is the development of a treatment response metric, days gained (DG). This metric is based on individual tumor kinetics estimated through segmented volumes of hyperintense regions on T1-weighted gadolinium-enhanced and T2-weighted magnetic resonance images. This metric was shown to be prognostic of time to progression. Furthermore, it was shown to be more prognostic of outcome than standard response metrics. Although promising, the original article did not account for uncertainty in the calculation of the DG metric, leaving the robustness of this cutoff in question. Methods We harnessed the Bayesian framework to consider the impact of two sources of uncertainty: (1) image acquisition and (2) interobserver error in image segmentation. We first used synthetic data to characterize what nonerror variants are influencing the final uncertainty in the DG metric. We then considered the original patient cohort to investigate clinical patterns of uncertainty and to determine how robust this metric is for predicting time to progression and overall survival. Results Our results indicate that the key clinical variants are the time between pretreatment images and the underlying tumor growth kinetics, matching our observations in the clinical cohort. Finally, we demonstrated that for this cohort, there was a continuous range of cutoffs between 94 and 105 for which the prediction of the time to progression was over 80% reliable. Conclusion Although additional validation must be performed, this work represents a key step in ascertaining the clinical utility of this metric.

scholarly journals Impact of Number of Segmented Tissues on SAR Prediction Accuracy in Deep Pelvic Hyperthermia Treatment Planning

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2646
Author(s):  
Iva VilasBoas-Ribeiro ◽  
Gerard C. van Rhoon ◽  
Tomas Drizdal ◽  
Martine Franckena ◽  
Margarethus M. Paulides
Keyword(s):  
Treatment Planning ◽  
High Water ◽  
Specific Model ◽  
Treatment Quality ◽  
Patient Specific ◽  
High Water Content ◽  
Treatment Optimization ◽  
Hyperthermia Treatment ◽  
Pre Treatment ◽  
The Impact

In hyperthermia, the general opinion is that pre-treatment optimization of treatment settings requires a patient-specific model. For deep pelvic hyperthermia treatment planning (HTP), tissue models comprising four tissue categories are currently discriminated. For head and neck HTP, we found that more tissues are required for increasing accuracy. In this work, we evaluated the impact of the number of segmented tissues on the predicted specific absorption rate (SAR) for the pelvic region. Highly detailed anatomical models of five healthy volunteers were selected from a virtual database. For each model, seven lists with varying levels of segmentation detail were defined and used as an input for a modeling study. SAR changes were quantified using the change in target-to-hotspot-quotient and maximum SAR relative differences, with respect to the most detailed patient model. The main finding of this study was that the inclusion of high water content tissues in the segmentation may result in a clinically relevant impact on the SAR distribution and on the predicted hyperthermia treatment quality when considering our pre-established thresholds. In general, our results underline the current clinical segmentation protocol and help to prioritize any improvements.

scholarly journals Pharmacological and Patient-Specific Response Determinants in Patients with Hospital-Acquired Pneumonia Treated with Tigecycline

2011 ◽  
Vol 56 (2) ◽  
pp. 1065-1072 ◽  
Author(s):  
Sujata M. Bhavnani ◽  
Christopher M. Rubino ◽  
Jeffrey P. Hammel ◽  
Alan Forrest ◽  
Nathalie Dartois ◽  
...  
Keyword(s):  
Clinical Success ◽  
Statistical Significance ◽  
Patient Specific ◽  
Specific Response ◽  
Multivariable Logistic Regression Model ◽  
Time Curve ◽  
Response Data ◽  
Hospital Acquired Pneumonia ◽  
Hospital Acquired ◽  
The Impact

ABSTRACTPharmacokinetic and clinical data from tigecycline-treated patients with hospital-acquired pneumonia (HAP) who were enrolled in a phase 3 clinical trial were integrated in order to evaluate pharmacokinetic-pharmacodynamic (PK-PD) relationships for efficacy. Univariable and multivariable analyses were conducted to identify factors associated with clinical and microbiological responses, based on data from 61 evaluable HAP patients who received tigecycline intravenously as a 100-mg loading dose followed by 50 mg every 12 h for a minimum of 7 days and for whom there were adequate clinical, pharmacokinetic, and response data. The final multivariable logistic regression model for clinical response contained albumin and the ratio of the free-drug area under the concentration-time curve from 0 to 24 h (fAUC0–24) to the MIC (fAUC0–24:MIC ratio). The odds of clinical success were 13.0 times higher for every 1-g/dl increase in albumin (P< 0.001) and 8.42 times higher for patients withfAUC0–24:MIC ratios of ≥0.9 compared to patients withfAUC0–24:MIC ratios of <0.9 (P= 0.008). Average model-estimated probabilities of clinical success for the albumin/fAUC0–24:MIC ratio combinations of <2.6/<0.9, <2.6/≥0.9, ≥2.6/<0.9, and ≥2.6/≥0.9 were 0.21, 0.57, 0.64, and 0.93, respectively. For microbiological response, the final model contained albumin and ventilator-associated pneumonia (VAP) status. The odds of microbiological success were 21.0 times higher for every 1-g/dl increase in albumin (P< 0.001) and 8.59 times higher for patients without VAP compared to those with VAP (P= 0.003). Among the remaining variables evaluated, the MIC had the greatest statistical significance, an observation which was not surprising given the differences in MIC distributions between VAP and non-VAP patients (MIC50and MIC90values of 0.5 and 0.25 mg/liter versus 16 and 1 mg/liter for VAP versus non-VAP patients, respectively;P= 0.006). These findings demonstrated the impact of pharmacological and patient-specific factors on the clinical and microbiological responses.

John Keats and Indian Medicine

Romanticism ◽  
2016 ◽  
Vol 22 (2) ◽  
pp. 157-166
Author(s):  
Nikki Hessell
Keyword(s):  
Medical Knowledge ◽  
John Keats ◽  
Specific Response ◽  
Medical Studies ◽  
Sources Of Information ◽  
Medical Practices ◽  
Traditional Medicines ◽  
Medical Imagery ◽  
Indian Medicine ◽  
The Impact

John Keats's medical studies at Guy's Hospital coincided with a boom in interest in both the traditional medicines of the sub-continent and the experiences of British doctors and patients in India. Despite extensive scholarship on the impact of Keats's medical knowledge on his poetry, little consideration has been given to Keats's exposure to Indian medicine. The poetry that followed his time at Guy's contains numerous references to the contemporary state of knowledge about India and its medical practices, both past and present. This essay focuses on Isabella and considers the major sources of information about Indian medicine in the Regency. It proposes that some of Keats's medical imagery might be read as a specific response to the debates about medicine in the sub-continent.

Uncovering the Diversification of Tissue Engineering on the Emergent Areas of Stem Cells, Nanotechnology and Biomaterials

2020 ◽  
Vol 15 (3) ◽  
pp. 187-201 ◽  
Author(s):  
Sunil K. Dubey ◽  
Amit Alexander ◽  
Munnangi Sivaram ◽  
Mukta Agrawal ◽  
Gautam Singhvi ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Stem Cells ◽  
Immune System ◽  
Clinical Application ◽  
Cell Types ◽  
Patient Specific ◽  
Potential Strategy ◽  
Induced Pluripotent ◽  
Treat All ◽  
The Impact

Damaged or disabled tissue is life-threatening due to the lack of proper treatment. Many conventional transplantation methods like autograft, iso-graft and allograft are in existence for ages, but they are not sufficient to treat all types of tissue or organ damages. Stem cells, with their unique capabilities like self-renewal and differentiate into various cell types, can be a potential strategy for tissue regeneration. However, the challenges like reproducibility, uncontrolled propagation and differentiation, isolation of specific kinds of cell and tumorigenic nature made these stem cells away from clinical application. Today, various types of stem cells like embryonic, fetal or gestational tissue, mesenchymal and induced-pluripotent stem cells are under investigation for their clinical application. Tissue engineering helps in configuring the stem cells to develop into a desired viable tissue, to use them clinically as a substitute for the conventional method. The use of stem cell-derived Extracellular Vesicles (EVs) is being studied to replace the stem cells, which decreases the immunological complications associated with the direct administration of stem cells. Tissue engineering also investigates various biomaterials to use clinically, either to replace the bones or as a scaffold to support the growth of stemcells/ tissue. Depending upon the need, there are various biomaterials like bio-ceramics, natural and synthetic biodegradable polymers to support replacement or regeneration of tissue. Like the other fields of science, tissue engineering is also incorporating the nanotechnology to develop nano-scaffolds to provide and support the growth of stem cells with an environment mimicking the Extracellular matrix (ECM) of the desired tissue. Tissue engineering is also used in the modulation of the immune system by using patient-specific Mesenchymal Stem Cells (MSCs) and by modifying the physical features of scaffolds that may provoke the immune system. This review describes the use of various stem cells, biomaterials and the impact of nanotechnology in regenerative medicine.

scholarly journals Pre-treatment clinical and gene expression patterns predict developmental change in early intervention in autism

2021 ◽  
Author(s):  
Michael V. Lombardo ◽  
Elena Maria Busuoli ◽  
Laura Schreibman ◽  
Aubyn C. Stahmer ◽  
Tiziano Pramparo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Treatment Outcome ◽  
Early Intervention ◽  
Developmental Change ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Time In Treatment ◽  
Pre Treatment ◽  
Blood Leukocyte ◽  
The Impact

AbstractEarly detection and intervention are believed to be key to facilitating better outcomes in children with autism, yet the impact of age at treatment start on the outcome is poorly understood. While clinical traits such as language ability have been shown to predict treatment outcome, whether or not and how information at the genomic level can predict treatment outcome is unknown. Leveraging a cohort of toddlers with autism who all received the same standardized intervention at a very young age and provided a blood sample, here we find that very early treatment engagement (i.e., <24 months) leads to greater gains while controlling for time in treatment. Pre-treatment clinical behavioral measures predict 21% of the variance in the rate of skill growth during early intervention. Pre-treatment blood leukocyte gene expression patterns also predict the rate of skill growth, accounting for 13% of the variance in treatment slopes. Results indicated that 295 genes can be prioritized as driving this effect. These treatment-relevant genes highly interact at the protein level, are enriched for differentially histone acetylated genes in autism postmortem cortical tissue, and are normatively highly expressed in a variety of subcortical and cortical areas important for social communication and language development. This work suggests that pre-treatment biological and clinical behavioral characteristics are important for predicting developmental change in the context of early intervention and that individualized pre-treatment biology related to histone acetylation may be key.

scholarly journals Time-to-Treatment in Oral Cancer: Causes and Implications for Survival

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1321
Author(s):  
Constanza Saka-Herrán ◽  
Enric Jané-Salas ◽  
Antoni Mari-Roig ◽  
Albert Estrugo-Devesa ◽  
José López-López
Keyword(s):  
Oral Cancer ◽  
Previous Treatment ◽  
Diagnostic Procedures ◽  
Original Data ◽  
Primary Treatment ◽  
Medical Attention ◽  
Time Interval ◽  
Pre Treatment ◽  
The Impact ◽  
Lack Of Knowledge

The purpose of this review was to identify and describe the causes that influence the time-intervals in the pathway of diagnosis and treatment of oral cancer and to assess its impact on prognosis and survival. The review was structured according to the recommendations of the Aarhus statement, considering original data from individual studies and systematic reviews that reported outcomes related to the patient, diagnostic and pre-treatment intervals. The patient interval is the major contributor to the total time-interval. Unawareness of signs and/or symptoms, denial and lack of knowledge about oral cancer are the major contributors to the process of seeking medical attention. The diagnostic interval is influenced by tumor factors, delays in referral due to higher number of consultations and previous treatment with different medicines or dental procedures and by professional factors such as experience and lack of knowledge related to the disease and diagnostic procedures. Patients with advanced stage disease, primary treatment with radiotherapy, treatment at an academic facility and transitions in care are associated with prolonged pre-treatment intervals. An emerging body of evidence supports the impact of prolonged pre-treatment and treatment intervals with poorer survival from oral cancer.

scholarly journals Comparison of Selected Immune and Hematological Parameters and Their Impact on Survival in Patients with HPV-Related and HPV-Unrelated Oropharyngeal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3256
Author(s):  
Adam Brewczyński ◽  
Beata Jabłońska ◽  
Agnieszka Maria Mazurek ◽  
Jolanta Mrochem-Kwarciak ◽  
Sławomir Mrowiec ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Oropharyngeal Cancer ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Post Treatment ◽  
Neutrophil Lymphocyte Ratio ◽  
Lymphocyte Ratio ◽  
Hpv Status ◽  
Pre Treatment ◽  
The Impact

Several immune and hematological parameters are associated with survival in patients with oropharyngeal cancer (OPC). The aim of the study was to analyze selected immune and hematological parameters of patients with HPV-related (HPV+) and HPV-unrelated (HPV-) OPC, before and after radiotherapy/chemoradiotherapy (RT/CRT) and to assess the impact of these parameters on survival. One hundred twenty seven patients with HPV+ and HPV− OPC, treated with RT alone or concurrent chemoradiotherapy (CRT), were included. Patients were divided according to HPV status. Confirmation of HPV etiology was obtained from FFPE (Formalin-Fixed, Paraffin-Embedded) tissue samples and/or extracellular circulating HPV DNA was determined. The pre-treatment and post-treatment laboratory blood parameters were compared in both groups. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), and systemic immune inflammation (SII) index were calculated. The impact of these parameters on overall (OS) and disease-free (DFS) survival was analyzed. In HPV+ patients, a high pre-treatment white blood cells (WBC) count (>8.33 /mm3), NLR (>2.13), SII (>448.60) significantly correlated with reduced OS, whereas high NLR (>2.29), SII (>462.58) significantly correlated with reduced DFS. A higher pre-treatment NLR and SII were significant poor prognostic factors for both OS and DFS in the HPV+ group. These associations were not apparent in HPV− patients. There are different pre-treatment and post-treatment immune and hematological prognostic factors for OS and DFS in HPV+ and HPV− patients. The immune ratios could be considered valuable biomarkers for risk stratification and differentiation for HPV− and HPV+ OPC patients.

scholarly journals Impact of a patient-specific national programme aimed at increasing the use of emollient moisturisers to reduce the risk of skin tears: a longitudinal cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. e039579
Author(s):  
Anna K Moffat ◽  
Kerrie P Westaway ◽  
Jemisha Apajee ◽  
Oliver Frank ◽  
Russell Shute ◽  
...  
Keyword(s):  
Interrupted Time Series ◽  
Self Report ◽  
Additional Patient ◽  
Patient Specific ◽  
Department Of Veterans Affairs ◽  
National Programme ◽  
Sustained Effect ◽  
Skin Tears ◽  
Comparison Groups ◽  
The Impact

ObjectivesTo evaluate the impact of a patient-specific national programme targeting older Australians and health professionals that aimed to increase use of emollient moisturisers to reduce to the risk of skin tears.DesignA prospective cohort intervention.ParticipantsThe intervention targeted 52 778 Australian Government’s Department of Veterans’ Affairs patients aged over 64 years who had risk factors for wound development, and their general practitioners (GPs) (n=14 178).Outcome measuresAn interrupted time series model compared the rate of dispensing of emollients in the targeted cohort before and up to 23 months after the intervention. Commitment questions were included in self-report forms.ResultsIn the first month after the intervention, the rate of claims increased 6.3-fold (95% CI: 5.2 to 7.6, p<0.001) to 10 emollient dispensings per 1000 patients in the first month after the intervention. Overall, the intervention resulted in 10 905 additional patient-months of treatment. The increased rate of dispensing among patients who committed to talking to their GP about using an emollient was six times higher (rate ratio: 6.2, 95% CI: 4.4 to 8.7) than comparison groups.ConclusionsThe intervention had a sustained effect over 23 months. Veterans who responded positively to commitment questions had higher uptake of emollients than those who did not.

scholarly journals Shooting from the ‘Scrip: Scope of Practice Laws and Access to Immunizations in the Pharmacy Setting

Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 444
Author(s):  
Charles Stoecker
Keyword(s):  
Positive Impact ◽  
National Level ◽  
State Level ◽  
The United States ◽  
Scope Of Practice ◽  
Patient Specific ◽  
Behavioral Risk ◽  
Influenza Immunization ◽  
Immunization Rates ◽  
The Impact

In the past two decades, most states in the United States have added authorization for pharmacists to administer some vaccinations. Expansions of this authority have also come with prescription requirements or other regulatory burdens. The objective of this study was to evaluate the impact of these expansions on influenza immunization rates in adults age 65 and over. A panel data, differences-in-differences regression framework to control for state-level unobserved confounders and shocks at the national level was used on a combination of a dataset of state-level statute and regulatory changes and influenza immunization data from the Behavioral Risk Factor Surveillance System. Giving pharmacists permission to vaccinate had a positive impact on adult influenza immunization rates of 1.4 percentage points for adults age 65 and over. This effect was diminished by the presence of laws requiring pharmacists to obtain patient-specific prescriptions. There was no evidence that allowing pharmacists to administer vaccinations led patients to have fewer annual check-ups with physicians or not have a usual source of health care. Expanding pharmacists’ scope of practice laws to include administering the influenza vaccine had a positive impact on influenza shot uptake. This may have implications for relaxing restrictions on other forms of care that could be provided by pharmacists.

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