scholarly journals Translational PBPK Modeling of the Protein Therapeutic and CD95L Inhibitor Asunercept to Develop Dose Recommendations for Its First Use in Pediatric Glioblastoma Patients

Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 152 ◽  
Author(s):  
Nina Hanke ◽  
Claudia Kunz ◽  
Meinolf Thiemann ◽  
Harald Fricke ◽  
Thorsten Lehr
Keyword(s):  
Body Weight ◽  
Clinical Investigation ◽  
Young Patients ◽  
Study Data ◽  
Pbpk Modeling ◽  
Dose Selection ◽  
Clinical Phase ◽  
Protein Therapeutic ◽  
Pediatric Glioblastoma ◽  
Dose Recommendations

The protein therapeutic and CD95L inhibitor asunercept is currently under clinical investigation for the treatment of glioblastoma and myelodysplastic syndrome. The purpose of this study was to predict the asunercept pharmacokinetics in children and to give dose recommendations for its first use in pediatric glioblastoma patients. A physiologically-based pharmacokinetic (PBPK) model of asunercept in healthy and diseased adults was successfully developed using the available clinical Phase I and Phase II study data. This model was then extrapolated to different pediatric populations, to predict the asunercept exposure in children and to find equivalent starting doses. Simulation of the asunercept serum concentration-time curves in children between 1–18 years of age shows that a dosing regimen based on body weight results in a similar asunercept steady-state exposure in all patients (pediatric or adult) above 12 years of age. For children between 1–12 years, higher doses per kg body weight are recommended, with the highest dose for the very young patients. Translational PBPK modeling is strongly encouraged by regulatory agencies to help with the initial dose selection for pediatric trials. To our knowledge, this is the first report of pediatric PBPK to support the dose selection of a therapeutic protein before its administration to children.

scholarly journals Characterisation of MS phenotypes across the age span using a novel data set integrating 34 clinical trials (NO.MS cohort): Age is a key contributor to presentation

2021 ◽  
pp. 135245852098863
Author(s):  
Frank Dahlke ◽  
Douglas L Arnold ◽  
Piet Aarden ◽  
Habib Ganjgahi ◽  
Dieter A Häring ◽  
...  
Keyword(s):  
Disease Activity ◽  
Brain Volume ◽  
Young Patients ◽  
Clinical Trial Data ◽  
Study Data ◽  
Phase Iii ◽  
Brain Images ◽  
Data Set ◽  
Brain Volume Loss ◽  
Phase Iii Study

Background: The Oxford Big Data Institute, multiple sclerosis (MS) physicians and Novartis aim to address unresolved questions in MS with a novel comprehensive clinical trial data set. Objective: The objective of this study is to describe the Novartis–Oxford MS (NO.MS) data set and to explore the relationships between age, disease activity and disease worsening across MS phenotypes. Methods: We report key characteristics of NO.MS. We modelled MS lesion formation, relapse frequency, brain volume change and disability worsening cross-sectionally, as a function of patients’ baseline age, using phase III study data (≈8000 patients). Results: NO.MS contains data of ≈35,000 patients (>200,000 brain images from ≈10,000 patients), with >10 years follow-up. (1) Focal disease activity is highest in paediatric patients and decreases with age, (2) brain volume loss is similar across age and phenotypes and (3) the youngest patients have the lowest likelihood (<25%) of disability worsening over 2 years while risk is higher (25%–75%) in older, disabled or progressive MS patients. Young patients benefit most from treatment. Conclusion: NO.MS will illuminate questions related to MS characterisation, progression and prognosis. Age modulates relapse frequency and, thus, the phenotypic presentation of MS. Disease worsening across all phenotypes is mediated by age and appears to some extent be independent from new focal inflammatory activity.

Effect of Sorafenib on Sex Hormone Levels in Male Swiss Albino Mice

2021 ◽  
pp. 3883-3888
Author(s):  
Surekha D. Shetty ◽  
Laxminarayana Bairy K. ◽  
AM Prasad ◽  
Satheesha Nayak B. ◽  
Ashwini Aithal P.
Keyword(s):  
Body Weight ◽  
Semen Analysis ◽  
Young Patients ◽  
Differentiated Thyroid Carcinoma ◽  
Positive Control ◽  
Vital Role ◽  
Reproductive Age ◽  
Control Group ◽  
Swiss Albino Mice ◽  
Albino Mice

Background: Hormones play a vital role in initiating and maintenance of male reproductive or testicular function which includes the production of androgens and spermatozoa. Testosterone is essential for the initiation and maintenance of spermatogenesis. FSH is responsible for the stimulation of spermatogenesis. Semen analysis and hormone evaluation are essential parameters in the diagnosis of infertility in males. Objective: The aim of the present study is to evaluate the effect of sorafenib on FSH and intratesticular testosterone levels in male Swiss albino mice. Materials and Methods: The animals were segregated into control, positive control, and treatment groups (n=6). Treatment group received 25, 50 and 100 mg/kg body weight of sorafenib orally for seven consecutive days at intervals of 24 hours between two administrations. Positive control group received 100 mg/kg body weight of imatinib. The animals were sacrificed at the end of 1st, 2nd, 4th, 5th, 7th and 10th week after the last exposure to sorafenib. Results: The intratesticular testosterone level was significantly (P<0.05) reduced in treated groups and severe effect was observed on week 4th and 5th weeks. FSH level was increased significantly (P<0.05) in sorafenib treated groups of mice. Conclusion: The administration of sorafenib does affect testosterone and FSH level significantly, but this effect is reversible once the drug is withdrawn. This finding may help the clinicians to plan and address the fertility-related issues in young patients of reproductive age who are being treated with sorafenib for advanced renal cell carcinoma, hepatocellular carcinoma and differentiated thyroid carcinoma.

scholarly journals Growth performance of 6th generation KUB-2 chicken

2021 ◽  
Vol 888 (1) ◽  
pp. 012015
Author(s):  
K Komarudin ◽  
T Sartika ◽  
N Pratiwi ◽  
T Kostaman
Keyword(s):  
Body Weight ◽  
Growth Performance ◽  
Egg Production ◽  
Study Data ◽  
Meat Production ◽  
Feed Conversion ◽  
Dual Purpose ◽  
Male And Female ◽  
Important Trait ◽  
Local Chicken

Abstract KUB-2 chicken is an improved local chicken originally from KUB-1 chicken. KUB-2 has been assembled in the Indonesian Research Institute for Animal Production (IRIAP), and it has two sub-populations, namely KUB-2 Balai and KUB-2 kk. KUB-2 has dual purpose functions, for either meat or egg production. For farmers who raise a local chicken to yield meat, growth is an important trait. The study had the objective to evaluate the growth performance of KUB-2 chicken. About 2,540 6th generation KUB-2 chickens, consisting of 1,240 KUB-2 Balai and 1,300 KUB-2 kk were used in the study. Data were analyzed using a t-test. The average ten-week body weight of male and female KUB-2 kk was statistically higher than KUB-2 Balai (P<0.05). The ten-week body weight of KUB-2 Balai and KUB-2 kk chickens were 1,045.91 g and 1,211.80 g for males, and 832.74 g and 956.02 g for females. The feed conversion was 2.81 for KUB-2 Balai and 2.83 for KUB-2 kk chicken. For meat production, KUB-2 kk seemed more profitable compared to KUB-2 Balai since it had higher body weight and similar feed conversion. It also could be yielded at shorter age than KUB-2 Balai for the same body weight.

scholarly journals Confounding Factors in the Interpretation of Preclinical Studies

2019 ◽  
Vol 38 (3) ◽  
pp. 228-234 ◽  
Author(s):  
Laura Dill Morton ◽  
Martin Sanders ◽  
William J. Reagan ◽  
Torrie A. Crabbs ◽  
Maralee McVean ◽  
...  
Keyword(s):  
Clinical Pathology ◽  
Early Death ◽  
Study Data ◽  
Dose Selection ◽  
Study Planning ◽  
Complicating Factors ◽  
Final Interpretation ◽  
Design Factors

A number of issues may arise during the conduct of a study which can complicate interpretation of in vitro and in vivo datasets. Speakers discussed the implications of differing interpretations and how to avoid complicating factors during study planning and execution. Consideration needs to be given to study design factors including defining objectives, consideration of expected pharmacological effects, dose selection and drug kinetics, species used, and vehicle selection. In addition, the effects of vivarium temperature effects on various endpoints, how to control variables affecting clinical pathology, and how early death animals, common background findings, and artifacts can affect histopathology interpretation all play into the final interpretation of study data.

Sexual function and satisfaction in Mexican young women undergoing breast cancer treatment.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e21714-e21714
Author(s):  
Cynthia Mayte Villarreal-Garza ◽  
Alejandra Platas ◽  
Andrea Castro-Sanchez ◽  
Melina Miaja ◽  
Alan Fonseca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Sexual Function ◽  
Young Women ◽  
Young Patients ◽  
Study Data ◽  
Mexican Women ◽  
Chi Square ◽  
Younger Women ◽  
Chi Square Test

e21714 Background: Compared to other regions, the burden of breast cancer (BC) in Mexico is disproportionately borne by younger women. Yet, their particular needs and concerns have remained understudied, including treatment-related sexual adverse effects. We aim to assess the sexual function and satisfaction in Mexican young women with BC undergoing treatment. Methods: This is a prospective sexual assessment study in BC patients of the pilot phase of the Joven y Fuerte Mexican cohort (N=96). Sexual health was assessed using the Female Sexual Function Index (FSFI) and the Sexual Satisfaction Inventory (SSI) at two points in time: baseline (BL) and 6-months follow-up (6-FU). FSFI and SSI scores lower than 26.55 and 111, respectively, were defined as sexual morbidity. Differences between proportions of BL and 6-FU were examined with Pearson chi-square test. Matched t-tests were used to test for differences in the domains of the FSFI and in the SSI total score. Results: 70 women completed the FSFI at both time points and 69 the SSI. Our results showed a high percentage of sexual dysfunction among Mexican women at BL and 6-FU (61.4% and 74.3%, respectively, p<0.001), as well as an elevated proportion of sexual low satisfaction at both time lines (40.6% and 43.5%, p=0.004). Most 6-FU FSFI domain scores were significantly worse than those at BL (Table 1). There were no significant differences in the SSI total score (102.31 [BL] vs 96.11 [6-FU], p=0.16). Conclusions: Mexican young patients with BC report significant sexual morbidity at BL, which even worsens after the first short follow-up. Reasons for the low sexual performance among Mexican women remain understudied and should be actively sought. In this prospective study, data will be annually collected for five years. This information will provide valuable information in an often-neglected matter of BC patients’ care. [Table: see text]

scholarly journals Pharmacokinetics of Ethionamide in Children

2011 ◽  
Vol 55 (10) ◽  
pp. 4594-4600 ◽  
Author(s):  
S. Thee ◽  
H. I. Seifart ◽  
B. Rosenkranz ◽  
A. C. Hesseling ◽  
K. Magdorf ◽  
...  
Keyword(s):  
Body Weight ◽  
Oral Dose ◽  
Age Groups ◽  
Serum Levels ◽  
Pharmacokinetic Parameters ◽  
Concomitant Treatment ◽  
Older Children ◽  
Maximum Serum ◽  
Antituberculosis Treatment ◽  
Dose Recommendations

ABSTRACTEthionamide (ETH), a second-line antituberculosis drug, is frequently used in treating childhood tuberculosis. Data supporting ETH dose recommendations in children are limited. The aim of this study was to determine the pharmacokinetic parameters for ETH in children on antituberculosis treatment including ETH. ETH serum levels were prospectively assessed in 31 children in 3 age groups (0 to 2 years, 2 to 6 years, and 6 to 12 years). Within each age group, half received rifampin (RMP). Following an oral dose of ETH (15 to 20 mg/kg of body weight), blood samples were collected at 0, 1, 2, 3, 4, and 6 h following 1 and 4 months of ETH therapy. The maximum serum concentration (Cmax), time toCmax(Tmax), and area under the time-concentration curve from 0 to 6 h (AUC0–6) were calculated. Younger children were exposed to lower ETH concentrations than older children at the same mg/kg body weight dose. Age correlated significantly with the AUC after both 1 month (r= 0.50,P= 0.001) and 4 months (r= 0.63,P= 0.001) of therapy. There was no difference in the AUC orCmaxbetween children receiving concomitant treatment with RMP and those who did not. Time on treatment did not influence the pharmacokinetic parameters of ETH following 1 and 4 months of therapy. HIV infection was associated with lower ETH exposure. In conclusion, ETH at an oral dose of 15 to 20 mg/kg results in sufficient serum concentrations compared to current adult recommended levels in the majority of children across all age groups. ETH levels were influenced by young age and HIV status but were not affected by concomitant RMP treatment and duration of therapy.

scholarly journals Double-Blind, Randomized, Three-Armed, Placebo-Controlled, Clinical Investigation to Evaluate the Benefit and Tolerability of Two Dosages of IQP-AE-103 in Reducing Body Weight in Overweight and Moderately Obese Subjects

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Ralf Uebelhack ◽  
Udo Bongartz ◽  
Stephanie Seibt ◽  
Gordana Bothe ◽  
Pee Win Chong ◽  
...  
Keyword(s):  
Weight Loss ◽  
Body Weight ◽  
Placebo Group ◽  
Body Fat ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Investigation ◽  
Controlled Trial ◽  
High Dose ◽  
Double Blind

Objective. This study was performed to determine the efficacy and tolerability/safety of IQP-AE-103 on body weight reduction in overweight to moderately obese adults. Methods. A double-blind, randomized, placebo-controlled trial involved one hundred and eight subjects (BMI between 25 and 35 kg/m2) that were randomly assigned to either the low-dose or the high-dose IQP-AE-103 group, or the placebo group. Following a 2-week run-in period, subjects received two capsules of investigational product after three daily main meals for 12 weeks. Subjects were instructed to maintain a nutritionally balanced hypocaloric diet according to the individual’s energy requirement. Body weight, body fat, and waist and hip circumference were measured at baseline, and after 2, 4, 8, and 12 weeks. Subjects also rated their feelings of hunger and fullness using visual analogue scales, and food craving on a 5-point scale at the same time intervals. Blood samplings for safety laboratory parameters were taken before and at the end of the study. Results. After 12 weeks of intake, the high-dose IQP-AE-103 group had a significantly greater weight loss compared with the placebo (5.03 ± 2.50 kg vs. 0.98 ± 2.06 kg, respectively; p<0.001) and the low-dose group (3.01 ± 2.19 kg; p=0.001). The high-dose group experienced a decrease in body fat of 3.15 ± 2.41 kg compared with a decrease of 0.23 ± 2.74 kg for the placebo group (p<0.001). High-dose IQP-AE-103 also decreased the feeling of hunger in 66% subjects. A beneficial effect of IQP-AE-103 on the lipid metabolism was also demonstrated in the subgroup of subjects with baseline total cholesterol levels above 6.2 mmol/L. No side effects related to the intake of IQP-AE-103 were reported. Conclusions. These findings indicate that IQP-AE-103 could be an effective and safe weight loss intervention. This trial is registered with NCT03058367.

scholarly journals The Spread of Caudal Analgesia in Children: A Mathematical Model

1986 ◽  
Vol 14 (2) ◽  
pp. 140-144 ◽  
Author(s):  
P. Busoni ◽  
T. Andreuccetti
Keyword(s):  
Mathematical Model ◽  
Body Weight ◽  
Local Anaesthetic ◽  
Young Patients ◽  
Older Children ◽  
Caudal Analgesia

A mathematical model correlating the spread of analgesia to the dose of local anaesthetic and to age or body weight was found analysing the data of 763 caudal blocks in children from age one day to twelve years. Two graphs have been plotted: (1) spread of analgesia, dose, age and (2) spread of analgesia, dose, weight. Both age and weight can be used as predictors to determine the desired level of analgesia, but weight is more useful in very young patients while age is a better guide in older children.

scholarly journals Potentially Preventable Deaths by Intensive Care Medicine in Mongolian Hospitals

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Naranpurev Mendsaikhan ◽  
Tsolmon Begzjav ◽  
Ganbold Lundeg ◽  
Martin W. Dünser
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Intensive Care Medicine ◽  
Young Patients ◽  
Study Data ◽  
Tertiary Level ◽  
Years Of Life Lost ◽  
Icu Admission ◽  
Observation Period ◽  
Do So

Purpose. To evaluate the portion of hospitalized patients dying without prior intensive care unit (ICU) admission and assess whether death could have been prevented by intensive care.Methods. In this prospective, observational, multicenter study, data of adults dying in and outside the ICU in 5 tertiary and 14 secondary hospitals were collected during six months. A group of experts categorized patients dying without prior ICU admission as whether their death was potentially preventable or not.Results. 617 patients died (72.9% in and 27.1% outside the ICU) during the observation period. In 54/113 patients (32.3%) dying in the hospital without prior ICU admission, death was considered potentially preventable. The highest number of these deaths was seen in patients aged 16–30 years and those who suffered from an infection (83.3%), underwent surgery (58.3%), or sustained trauma (52%). Potentially preventable deaths resulted in a total number of 1,078 years of life lost and 709 productive years of life lost.Conclusions. Twenty-seven percent of adults dying in Mongolian secondary and tertiary level hospitals do so without prior ICU admission. One-third, mostly young patients suffering from acute reversible conditions, may have potentially been saved by intensive care medicine.

Sign in / Sign up

Export Citation Format

Share Document