Dose Adjustment of Quetiapine and Aripiprazole for Pregnant Women Using Physiologically Based Pharmacokinetic Modeling and Simulation

xlomafota.13 shared this article with you from Inoreader Dose Adjustment of Quetiapine and Aripiprazole for Pregnant Women Using Physiologically Based Pharmacokinetic Modeling and Simulation Via Latest Results for Clinical Pharmacokinetics Abstract Background and Objective Quetiapine and aripiprazole are currently prescribed for pregnant women to treat schizophrenia and bipolar disorder. A dramlatic decline in the plasma concentrations of these two drugs was observed if the doses remained fixed throughout pregnancy. This study aims to develop physiologically based pharmacokinetic (PBPK) models to predict the pharmacokinetics of quetiapine, aripiprazole, and the active aripiprazole metabolite dehydroaripiprazole during pregnancy. Methods We developed models using a combined 'bottom-up' and 'top-down' strategy. Models were verified by assessing goodness-of-fit plots and ratios of predicted-to-observed pharmacokinetic parameters. To extrapolate to pregnancy, we considered anatomical, physiological, and metabolic alterations. The in silico models were applied to predict steady-state pharmacokinetics in the three stages of pregnancy and to inform dose selection. Results We successfully constructed PBPK models that accurately predicted the pharmacokinetics of drugs in the adult population. Predictions suggested that the area under the concentration–time curve at steady state in the first, second, and third trimesters, respectively, decreased by 8.7%, 35.0%, and 49.1% for quetiapine and 12.6%, 38.8%, and 60.9% for the active moiety of aripiprazole. The third-trimester plasma concentrations of quetiapine were below the lower limit of the therapeutic range (100 ng/mL) for most of the time interval, and aripiprazole was entirely unable to reach its effective concentration (150 ng/mL). Conclusions According to PBPK predictions, the doses should be increased in the latter two trimesters. We generally recommend that women during late pregnancy take at least 2.5- and 2-times their baseline doses of quetiapine and aripiprazole, respectively. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effect of manual aspiration thrombectomy using large-bore aspiration catheter for acute basilar artery occlusion: comparison with a stent retriever system

xlomafota.13 shared this article with you from Inoreader Effect of manual aspiration thrombectomy using large-bore aspiration catheter for acute basilar artery occlusion: comparison with a stent retriever system Via Latest Results for BMC Neurology Abstract Background A large-bore aspiration catheter can be employed for recanalization of acute basilar artery occlusion. Here we compare the results of mechanical thrombectomy using a stent retriever (SR) and manual aspiration thrombectomy (MAT) using a large-bore aspiration catheter system as a first-line recanalization method in acute basilar artery occlusion (BAO). Methods The records of 50 patients with acute BAO who underwent mechanical thrombectomy were retrospectively reviewed. Patients were assigned to one of two groups based on the first-line recanalization method. The treatment and clinical outcomes were compared. Results Sixteen (32%) patients were treated with MAT with a large-bore aspiration catheter and 34 (68%) with a SR as the first-line treatment method. The MAT group had a shorter procedure time (28 vs. 65 min; p = 0.001), higher rate of first-pass recanalization (68.8% vs. 38.2%, p = 0.044), and lower median number of passes (1 vs 2; p = 0.008) when compared with the SR group. There was no significant difference in the incidence of any hemorrhagic complication (6.3% vs. 8.8%; p = 0.754) between the groups. However, there were four cases of procedure-related subarachnoid hemorrhage (SAH) in the SR group and one death occurred due to massive hemorrhage. Conclusions Selection of MAT using a large-bore aspiration catheter for acute BAO may be a safe and effective first-line treatment method with higher first-pass recanalization rate and shorter procedure time than SR. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Erenumab efficacy in highly resistant chronic migraine

xlomafota.13 shared this article with you from Inoreader Erenumab efficacy in highly resistant chronic migraine: a real-life study Via Latest Results for Neurological Sciences View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy of erenumab 70 mg in chronic migraine: Vicenza experience

xlomafota.13 shared this article with you from Inoreader Efficacy of erenumab 70 mg in chronic migraine: Vicenza experience Via Latest Results for Neurological Sciences View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Conversion from a failed proximal femoral nail anti-rotation to a cemented or uncemented total hip arthroplasty device: a retrospective review of 198 hips with previous intertrochanteric femur fractures

xlomafota.13 shared this article with you from Inoreader Conversion from a failed proximal femoral nail anti-rotation to a cemented or uncemented total hip arthroplasty device: a retrospective review of 198 hips with previous intertrochanteric femur fractures Via Latest Results for BMC Musculoskeletal Disorders Abstract Background At present, it is unclear which device (uncemented or cemented total hip arthroplasty [UTA or CTA, respectively]) is more suitable for the conversion of a failed proximal femoral nail anti-rotation (PFNA). The aim of this review was to assess the outcomes of failed PFNAs converted to a UTA or CTA device in elderly individuals with intertrochanteric femoral fractures (IFFs). Methods Two hundred fifty-eight elderly individuals (258 hips) with IFFs who underwent a conversion to a UTA or CTA device following failed PFNAs during 2007–2017 were retrospectively identified from the China Southern Medical Centre (CSMC) database. The primary endpoint was the Harris Hip Score (HHS); secondary endpoint was the key orthopaedic complication rate. Results The median follow-up was 65 months (60–69 months). Significant distinctions were observed (87.26 ± 16.62 for UTA vs. 89.32 ± 16.08 for CTA, p = 0.021; 86.61 ± 12.24 for symptomatic UTA vs. 88.68 ± 13.30 for symptomatic CTA, p = 0.026). A significant difference in the overall key orthopaedic complication rate was detected (40.8% [40/98] vs. 19.0% [19/100], p = 0.001). Apparent distinctions were detected in terms of the rate of revision, loosening, and periprosthetic fracture (11.2% for UTA vs 3.0% for CTA, p = 0.025; 13.2% for UTA vs 5.0% for CTA, p = 0.043; 10.2% for UTA vs 3.0% for CTA, p = 0.041, respectively). Conclusion For elderly individuals with IFFs who suffered a failed PFNA, CTA devices may have a noteworthy advantage in regard to the revision rate and the rate of key orthopaedic complications compared with UTA devices, and CTA revision should be performed as soon as possible, regardless of whether these individuals have symptoms. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Fibronectin/thermo-responsive polymer scaffold as a dynamic ex vivo niche for mesenchymal stem cells

xlomafota.13 shared this article with you from Inoreader Fibronectin/thermo-responsive polymer scaffold as a dynamic ex vivo niche for mesenchymal stem cells Via Latest Results for Journal of Materials Science: Materials in Medicine Abstract In this paper, we created a dynamic adhesive environment (DAE) for adipose tissue-derived mesenchymal stem cells (ADMSCs) cultured on smart thermo-responsive substrates, i.e., poly (N-isopropyl acrylamide) (PNIPAM), via introducing periodic changes in the culture temperature. We further explored the particular role of adsorbed fibronectin (FN), an important cell adhesive protein that was recently attributed to the recruitment of stem cells in the niche. The engineered FN/PNIPAM DAE system significantly increased the symmetric renewal of ADMSCs, particularly between passages 7 and 9 (p7–p9), before it dropped down to the level of the control (FN-coated TC polystyrene). This decline in the growth curve was consistent with the increased number of senescent cells, the augmented average cell size and the suppressed FN matrix secretion at late passages (p10–p12), all of them characteristic for stem cells ageing, which equivocally tended to slow down at our DAE sy stem. FN supported also the osteogenic response of ADMSCs (apart from the previous observations with plain PNIPAM substrata) indicated by the significant increase of alkaline phosphatase (ALP) activity at days 7 and 14. The minimal changes in the Ca deposition, however, suggest a restricted effect of DAE on the early osteogenic response of ADMSCs only. Thus, the engineering of niche-like DAE involving FN uncovers a new tissue engineering strategy for gaining larger amounts of functionally active stem cells for clinical application. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Coaction of TGF-β1 and CDMP1 in BMSCs-induced laryngeal cartilage repair in rabbits

xlomafota.13 shared this article with you from Inoreader Coaction of TGF-β1 and CDMP1 in BMSCs-induced laryngeal cartilage repair in rabbits Via Latest Results for Journal of Materials Science: Materials in Medicine Abstract Bone marrow mesenchymal stem cells (BMSCs) are well-known for tissue regeneration and bone repair. This study intended to evaluate the potential efficiency BMSCs in poly(lactide-co-glycolide) (PLGA) scaffolds for the treatment of laryngeal cartilage defects. BMSCs were isolated and identified, and added with 10 ng/mL transforming growth factor-beta1 (TGF-β1) or/and 300 ng/mL CDMP1 to coculture with PLGA scaffolds. The chondrogenic differentiation, migration, and apoptosis of BMSCs were detected under the action of TGF-β1 or/and CDMP1. After successful modeling of laryngeal cartilage defects, PLGA scaffolds were transplanted into the rabbits correspondingly. After 8 weeks, laryngeal cartilage defects were assessed. Levels of collagen II, aggrecan, Sox9, Smad2, Smad3, ERK, and JNK were detected. The TGF-β1 or/and CDMP1-induced BMSCs expressed collagen II, aggrecan, and Sox9, with enhanced cell migration and inhibited apoptosis. In addition, laryngeal carti lage defect in rabbits with TGF-β1 or/and CDMP1 was alleviated, and levels of specific cartilage matrix markers were decreased. The combined effects of TGF-β1 and CDMP1 were more significant. The TGF-β1/Smad and ERK/JNK pathways were activated after TGF-β1 or/and CDMP1 were added to BMSCs or rabbits. In summary, BMSCs and PLGA scaffolds repair laryngeal cartilage defects in rabbits by activating the TGF-β1/Smad and ERK/JNK pathways under the coaction of TGF-β1 and CDMP1. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Risk factors for cement leakage and nomogram for predicting the intradiscal cement leakage after the vertebra augmented surgery

xlomafota.13 shared this article with you from Inoreader Risk factors for cement leakage and nomogram for predicting the intradiscal cement leakage after the vertebra augmented surgery Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Vertebral augmentation is the first-line treatment for the osteoporosis vertebral compression fractures. Bone cement leakage is the most common complication of this surgery. This study aims to assess the risk factors for different types of cement leakage and provides a nomogram for predicting the cement intradiscal leakage. Methods We retrospectively reviewed 268 patients who underwent vertebral augmentation procedure between January 2015 and March 2019. The cement leakage risk factors were evaluated by univariate analysis. Different types of cement leakage risk factors were identified by the stepwise logistic analysis. We provided a nomogram for predicting the cement intradiscal leakage and used the concordance index to assess the prediction ability. Results A total of 295 levels of vertebrae were included, with a leakage rate of 32.5%. Univariate analysis showed delayed surgery and lower vertebral compression ratio were the independent risk factors of cement leakage. The stepwise logistic analysis revealed percutaneous vertebroplasty was a risk factor in vein cement leakage; delayed surgery, preoperative compression ratio, and upper endplate disruption were in intradiscal cement leakage; age, preoperative fracture severity, and intravertebral vacuum cleft were in perivertebral soft tissue cement leakage; no factor was in spinal canal cement leakage. The nomogram for intradiscal cement leakage had a precise prediction ability with an original concordance index of 0.75. Conclusions Delayed surgery and more vertebral compression increase the risk of cement leakage. Different types of cement leakage have different risk factors. We provided a nomogram for precise predicting the intradiscal cement leakage. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Reliability of tibiofemoral contact area and centroid location in upright, open MRI

xlomafota.13 shared this article with you from Inoreader Reliability of tibiofemoral contact area and centroid location in upright, open MRI Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Imaging cannot be performed during natural weightbearing in biomechanical studies using conventional closed-bore MRI, which has necessitated simulating weightbearing load on the joint. Upright, open MRI (UO-MRI) allows for joint imaging during natural weightbearing and may have the potential to better characterize the biomechanical effect of tibiofemoral pathology involving soft tissues. However open MRI scanners have lower field strengths than closed-bore scanners, which limits the image quality that can be obtained. Thus, there is a need to establish the reliability of measurements in upright weightbearing postures obtained using UO-MRI. Methods Knees of five participants with prior anterior cruciate ligament (ACL) rupture were scanned standing in a 0.5 T upright open MRI scanner using a 3D DESS sequence. Manual segmentation of cartilage regions in contact was performed and centroids of these contact areas were automatically determined for the medial and lateral tibiofemoral compartments. Inter-rater, test-retest, and intra-rater reliability were determined and quantified using intra-class correlation (ICC3,1), standard error of measurement (SEM), and smallest detectable change with 95% confidence (SDC95). Accuracy was assessed by using a high-resolution 7 T MRI as a reference. Results Contact area and centroid location reliability (inter-rater, test-retest, and intra-rater) for sagittal scans in the medial compartment had ICC3,1 values from 0.95–0.99 and 0.98–0.99 respectively. In the lateral compartment, contact area and centroid location reliability ICC3,1 values ranged from 0.83–0.91 and 0.95–1.00 respectively. The smallest detectable change in contact area was 1.28% in the medial compartment and 0.95% in the lateral compartment. Contact area and centroid location reliability for coronal scans in the medial compartment had ICC3,1 values from 0.90–0.98 and 0.98–1.00 respectively, and in the lateral compartment ICC3,1 ranged from 0.76–0.94 and 0.93–1.00 respectively. The smallest detectable change in contact area was 0.65% in the medial compartment and 1.41% in the lateral compartment. Contact area was accurate to within a mean absolute error of 11.0 mm2. Conclusions Knee contact area and contact centroid location can be assessed in upright weightbearing MRI with good to excellent reliability. The lower field strength used in upright, weightbearing MRI does not compromise the reliability of tibiofemoral contact area and centroid location measures. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Orofaciodigital syndrome type II (Mohr syndrome

xlomafota.13 shared this article with you from Inoreader Orofaciodigital syndrome type II (Mohr syndrome): a case report Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Orofacial digital syndrome is a rare genetic disorder with oral cavity, facial and digits anomalies. Orofacial digital syndrome type II, also called the "Mohr syndrome" is a very rare subtype that has been reported scarcely in Asia especially in Japanese patients. Case presentation The case is an Iranian 5-year old girl who had been admitted for orthopedic surgery. She surprisingly had pre and postaxial polydactyly of all the four limbs concurrent with syndromic face and most of the features of Orofaciodigital syndrome type II. Conclusion Mohr syndrome, anesthesia and surgical considerations are discussed in this case report. It is recommended to consider these considerations and the possibility of OFDS in every child with pre and postaxial polydactyly of the four limbs and to try to distinguish type II from other types of ODFS. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Effects of a movement control and tactile acuity training in patients with nonspecific chronic low back pain and control impairment – a randomised controlled pilot study

xlomafota.13 shared this article with you from Inoreader Effects of a movement control and tactile acuity training in patients with nonspecific chronic low back pain and control impairment – a randomised controlled pilot study Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Nonspecific chronic low back pain (NSCLBP) is a heterogeneous condition that is associated with complex neuromuscular adaptations. Exercise is a widely administered treatment, but its effects are small to moderate. Tailoring patient-specific exercise treatments based on subgroup classification may improve patient outcomes. Objective In this randomised controlled pilot study, our objective was to compare the feasibility and possible effects of a specific sensorimotor treatment (SMT) with those of a general exercise (GE) programme on patients with NSCLBP and control impairment (CI). Methods Patients with NSCLBP and CI were randomised into an SMT or a GE programme spanning 6 sessions each. The feasibility criteria included the study design, assessments, interventions and magnitudes of effects, and costs. Adverse events were documented. Primary (pain, physical function, and quality of life) and secondary outcomes were assessed three times: twice at baseline (t1a and t1b) to estimate parameter stability and once after the intervention (t2). Results Two-hundred and twenty-seven patients were screened to include 34 participants with NSCLBP and CI. Both treatment programmes and the assessments seemed feasible because their durations and contents were perceived as adequate. The total cost per participant was €321. Two adverse events occurred (one not likely related to the SMT, one likely related to the GE intervention). The SMT showed a tendency for superior effects in terms of pain severity (SMT t1a 3.5, t2 1.1; GE t1a 3.0, t2 2.0), pain interference (SMT t1a 1.9, t2 0.4; GE t1a 1.5, t2 0.9), physical component of quality of life (SMT t1a 39, t2 46; GE t1a 45, t2 48), and movement control. Conclusions The SMT approach proposed in this study is feasible and should be tested thoroughly in future studies, possibly as an addition to GE. To ensure the detection of differences in pain severity between SMT and GE in patients with NSCLBP with 80% power, future studies should include 110 patients. If the current results are confirmed, SMT should be considered in interventions for patients with NSCLBP and CI. Trial registration Registered in the German Register for Clinical Trials (Trial registration date: November 11, 2016; Trial registration number: DRKS00011063; URL of trial registry record); retrospectively registered. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.