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.

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.

scholarly journals Ovarian tissue freezing and activation after thawing: an update

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Li-fan Peng
Keyword(s):  
Granulosa Cells ◽  
Clinical Decision Making ◽  
Ovarian Function ◽  
Ovarian Tissue ◽  
Clinical Decision ◽  
The Body ◽  
Endocrine Function ◽  
Ovarian Tissue Cryopreservation ◽  
Main Body ◽  
Tissue Cryopreservation

Abstract Background With the growth of women’s age, ovarian failure can be caused by various factors. For the women who need chemotherapy because of cancer factors, the preservation of fertility is more urgent. The treatment of cancer is also a process in which all tissues and organs of the body are severely damaged, especially in the reproductive system. Main body As a new fertility preservation technology, autologous ovarian tissue cryopreservation and transplantation is developing rapidly and showing great potentiality in preserving ovarian endocrine function of young cervical cancer patients. Vitrification and slow freezing are two common techniques applied for ovarian tissue cryopreservation. Thus, cryopreserved/thawed ovarian tissue and transplantation act as an important method to preserve ovarian function during radiotherapy and chemotherapy, and ovarian cryopreservation by vitrification is a very effective and extensively used method to cryopreserve ovaries. The morphology of oocytes and granulosa cells and the structure of organelles were observed under the microscope of histology; the hormone content in the stratified culture medium of granulosa cells with the diameter of follicle was used to evaluate the development potential of ovarian tissue, and finally the ovarian tissue stimulation was determined by the technique of ovarian tissue transplantation. Conclusions Although there are some limitations, the team members still carry out this review to provide some references and suggestions for clinical decision-making and further clinical research.

scholarly journals Awareness, Knowledge, and Utility of RCT Data vs RWE: Results From a Survey of US Cardiologists: Real-world Evidence in Clinical Decision Making

2020 ◽  
Vol 14 ◽  
pp. 117954682095341 ◽  
Author(s):  
Todd C Villines ◽  
Mark J Cziraky ◽  
Alpesh N Amin
Keyword(s):  
Decision Making ◽  
Clinical Practice ◽  
Real World ◽  
Randomized Clinical Trials ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
The Body ◽  
Representative Sampling ◽  
Real World Evidence ◽  
Wide Range

Real-world evidence (RWE) provides a potential rich source of additional information to the body of data available from randomized clinical trials (RCTs), but there is a need to understand the strengths and limitations of RWE before it can be applied to clinical practice. To gain insight into current thinking in clinical decision making and utility of different data sources, a representative sampling of US cardiologists selected from the current, active Fellows of the American College of Cardiology (ACC) were surveyed to evaluate their perceptions of findings from RCTs and RWE studies and their application in clinical practice. The survey was conducted online via the ACC web portal between 12 July and 11 August 2017. Of the 548 active ACC Fellows invited as panel members, 173 completed the survey (32% response), most of whom were board certified in general cardiology (n = 119, 69%) or interventional cardiology (n = 40, 23%). The survey results indicated a wide range of familiarity with and utilization of RWE amongst cardiologists. Most cardiologists were familiar with RWE and considered RWE in clinical practice at least some of the time. However, a significant minority of survey respondents had rarely or never applied RWE learnings in their clinical practice, and many did not feel confident in the results of RWE other than registry data. These survey findings suggest that additional education on how to assess and interpret RWE could help physicians to integrate data and learnings from RCTs and RWE to best guide clinical decision making.

scholarly journals Genetics of Biliary Tract Cancers and Emerging Targeted Therapies

2010 ◽  
Vol 28 (21) ◽  
pp. 3531-3540 ◽  
Author(s):  
Aram F. Hezel ◽  
Vikram Deshpande ◽  
Andrew X. Zhu
Keyword(s):  
Clinical Trials ◽  
Biliary Tract ◽  
Targeted Therapies ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Individual Treatment ◽  
Biliary Tract Cancers ◽  
Animal Modeling ◽  
Treatment Regimens ◽  
Tumor Genetics

Biliary tract cancers (BTC), which encompass intra- and extrahepatic cholangiocarcinomas and gallbladder carcinomas, are a genetically diverse collection of cancers. Evidence suggests distinct models of molecular and pathologic progression, and a growing body of genetics data points to a heterogeneous collection of underlying mutations in key oncogenes and tumor suppressor genes. Although tumor genetics have been used to tailor individual treatment regimens and guide clinical decision making in other cancers, these principles have not been applied in BTC. Recent clinical trials with targeted therapies seem promising, although the relationships between subsets of patients with positive responses to therapy and tumor genetics remain unexplored. Here, we summarize the molecular pathogenesis and genetics of BTCs and animal modeling and relate these to recent and ongoing clinical trials with targeted agents.

scholarly journals Effectiveness of Mulligan joint mobilizations and trunk stabilization exercises versus isometric knee strengthening in the management of knee osteoarthritis: study protocol for a randomized controlled trial

2020 ◽  
Author(s):  
Shaikh Nabi Bukhsh Nazir ◽  
Syed Shahzad Ali ◽  
Saeed Akhtar
Keyword(s):  
Knee Osteoarthritis ◽  
Study Protocol ◽  
Clinical Decision Making ◽  
Negative Impact ◽  
Controlled Trial ◽  
Movement Control ◽  
Clinical Decision ◽  
The Body ◽  
Study Objective ◽  
Trunk Stabilization

AbstractKnee Osteoarthritis (KOA) patients have a huge negative impact on gait parameters and altered biomechanics in many components, including impairments of dynamic lower limb alignment and lumbopelvic movement control. The understanding of these components seems to be very crucial and there is need to add these unfocused components in treatment regimens in the research setting to see its effects; before using as a routine treatment regime in Clinical practice for patients with KOA. This study protocol focuses on whether Mulligan joint mobilization with movement provides evident effects on decreasing pain and restoring the joint biomechanics. Trunk stabilization exercises improve the stability of the trunk which distributes the weight of the body evenly on both feet biomechanically. The treatment effects of both treatments are inconclusive. Accordingly, the study aims to determine the efficacy of Mulligan joint mobilizations and trunk stabilization exercises versus isometric knee strengthening for KOA. It is a study protocol of a three-arm randomized control trial. Initial screening of the subjects will be carried out by a referring consultant. Subjects who fulfill the study criteria will be randomly allocated into three groups After an explanation of study objective and obtaining informed consent. Group 1 will receive mulligan mobilization with kinesiotaping and knee strengthening. Group 2 will receive trunk stabilization exercise, knee strengthening, and Kinesiotaping. Group 3 will receive knee strengthening along with kinesiotaping. All participants will be evaluated using visual analogue scale, Knee injury and Osteoarthritis Outcome Score, stair climb test and 6-minute walk test at 1st, 3rd and 6th week. The results of this study will answer a clearly focused question investigated in KOA patients. Finding of this study will serve as a guide to inform clinical decision making for healthcare professionals, researcher, and patients.Trial registrationNCT04099017

scholarly journals Effectiveness of Mulligan Joint Mobilizations and Trunk Stabilization Exercises Versus Isometric Knee Strengthening in the Management of Knee Osteoarthritis: Study Protocol for a Randomized Controlled Trial.

2020 ◽  
Author(s):  
SHAIKH NABI BUKHSH NAZIR ◽  
Syed Shahzad Ali ◽  
Saeed Akhtar
Keyword(s):  
Randomized Controlled Trial ◽  
Study Protocol ◽  
Clinical Decision Making ◽  
Negative Impact ◽  
Controlled Trial ◽  
Clinical Decision ◽  
The Body ◽  
Study Objective ◽  
Randomized Controlled ◽  
Trunk Stabilization

Abstract BackgroundKnee Osteoarthritis (KOA) has a huge negative impact on gait parameters and on many components of biomechanics, including impairment of dynamic lower limb alignment and control of lumbopelvic movement. Specifically addressing these problems in treatment regimens is therefore critical but they must first be studied in detail before they can be used clinically to treat patients with KOA. This study protocol focuses on whether Mulligan joint mobilization with movement demonstrably decreases pain and restores healthy joint biomechanics and whether trunk stabilization exercises improve stability of the trunk, thereby distributing the weight of the body evenly on both feet. Because the treatment effects of neither treatment are conclusive, this study aims to determine their efficacy versus isometric knee strengthening.Method:The study protocol is a three-arm randomized controlled trial. After initial screening by a referring consultant, subjects who fulfil the study criteria will be randomly assigned to one of three groups. They will then be given an explanation of study objective and asked for their informed consent to participate in the study. Group 1 will receive Mulligan mobilization with kinesiotaping and knee strengthening. Group 2 will receive trunk stabilization exercises, knee strengthening, and kinesiotaping. Group 3 will receive knee strengthening along with kinesiotaping. All participants will be evaluated using a visual analogue scale, Knee injury and Osteoarthritis Outcome Score, stair climb test and 6-minute walk test at the baseline, 3rd and end of 6th week.DiscussionThe results of this study will answer focused questions concerning the relative efficacy of each treatment in KOA patients. The findings of this study will inform clinical decision-making by healthcare professionals and researchers.Trial registration: NCT04099017

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.

scholarly journals Orientation-Invariant Spatio-Temporal Gait Analysis Using Foot-Worn Inertial Sensors

Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3940
Author(s):  
Vânia Guimarães ◽  
Inês Sousa ◽  
Miguel Velhote Correia
Keyword(s):  
Gait Analysis ◽  
Relative Error ◽  
Clinical Decision Making ◽  
Inertial Sensors ◽  
Clinical Decision ◽  
The Body ◽  
Sensor Data ◽  
Sensor Orientation ◽  
Optical Motion ◽  
Spatio Temporal

Inertial sensors can potentially assist clinical decision making in gait-related disorders. Methods for objective spatio-temporal gait analysis usually assume the careful alignment of the sensors on the body, so that sensor data can be evaluated using the body coordinate system. Some studies infer sensor orientation by exploring the cyclic characteristics of walking. In addition to being unrealistic to assume that the sensor can be aligned perfectly with the body, the robustness of gait analysis with respect to differences in sensor orientation has not yet been investigated—potentially hindering use in clinical settings. To address this gap in the literature, we introduce an orientation-invariant gait analysis approach and propose a method to quantitatively assess robustness to changes in sensor orientation. We validate our results in a group of young adults, using an optical motion capture system as reference. Overall, good agreement between systems is achieved considering an extensive set of gait metrics. Gait speed is evaluated with a relative error of −3.1±9.2 cm/s, but precision improves when turning strides are excluded from the analysis, resulting in a relative error of −3.4±6.9 cm/s. We demonstrate the invariance of our approach by simulating rotations of the sensor on the foot.

Sign in / Sign up

Export Citation Format

Share Document