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2021 ◽  
Author(s):  
Jose de Leon ◽  
Georgios Schoretsanitis ◽  
Robert L. Smith ◽  
Espen Molden ◽  
Anssi Solismaa ◽  
...  

AbstractThis international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.


iScience ◽  
2021 ◽  
pp. 103665
Author(s):  
Nicholas W. Bateman ◽  
Christopher M. Tarney ◽  
Tamara S. Abulez ◽  
Brian L. Hood ◽  
Kelly A. Conrads ◽  
...  

2021 ◽  
Vol 51 ◽  
pp. e210-e211
Author(s):  
Jessica O'Loughlin ◽  
Francesco Casanova ◽  
Amanda Hughes ◽  
Jack Bowden ◽  
Edward Watkins ◽  
...  

Author(s):  
Olga Giannakopoulou ◽  
Kuang Lin ◽  
Xiangrui Meng ◽  
Mei-Hsin Su ◽  
Po-Hsiu Kuo ◽  
...  

2021 ◽  
Author(s):  
Charles A Hay ◽  
James A Prior ◽  
Christian D Mallen ◽  
John Belcher ◽  
Ed Roddy

2021 ◽  
pp. 112067212110356
Author(s):  
Yue Ma ◽  
Meiting Tang ◽  
Don O Kikkawa ◽  
Wei Lu

Purpose: This study evaluates causes and treatment of lower eyelid retraction with co-existing entropion in Thyroid Eye Disease (TED) patients of East Asian ancestry. Methods: The medical records for 25 eyelids from 15 TED patients with lower eyelid retraction and entropion who had undergone combined orbital decompression and lower eyelid retraction correction surgery at the Second Hospital of Dalian Medical University from January 2017 to December 2018 were prospectively reviewed. We build a numerical model of biomechanics to analyze von Mises stress and displacement at the lower eyelid. Results: The mean follow-up duration was 6 ± 2 months. The difference of mean exophthalmos was 5.16 ± 1.21 mm ( t = 21.26, p = 4.479E-17 < 0.05). The difference of mean MRD2 was 1.9 ± 0.14 mm ( t = 67.57, p = 6.751E-29 < 0.05). About 2 of 25 eyelids entropion recurred postoperatively; the overall success rate was 92%. The biomechanical analysis results reveal that the eyelid margin is given more stress and caused more displacement in East Asian ancestry under the same force of pressure. Conclusions: This study shows that the lower eyelid retraction with coexistent entropion is attributable to the unique anatomical features of patients of East Asians ancestry. We corrected the lower eyelid retraction and entropion during the orbital decompression operation. The results show that this method is safe and effective. It can simultaneously improve the symptoms of TED patients such as exophthalmos, lower eyelid retraction, and entropion, with minimal complications.


2021 ◽  
Author(s):  
Svetoslav Stamov

We report the presence of significant Central Asian ancestry in both contemporary Bulgarians and in early medieval population from SMC (Saltovo Mayaky Culture). The existence of Chalcolithic Iran (Hajj Fruz) and Wusun related ancestral component in contemporary Bulgarians comes as a surprise and sheds light on both migration route and ethnic origins of ProtoBulgarians. We interpret these results as an evidence for a Central Asian connection for the tribes, constituting the population of SMC and Kubrats Old Great Bulgaria in Pontic steppe from 6th and 7th century AD. We identify Central Asian Wusun tribes as carriers of this component on the base from the results from f3 and D statistics. We suggest that Wusun related tribes must have played role (or might have even been the backbone) in what became known as the Hunnic migration to Europe during 3rd 5th century AD. Same population must have taken part in the formation of the SMC (Saltovo Mayaki Culture) and Great Old Bulgarian during 6th 9th century AD in Pontic Caspian steppe. We also explore the genomic origins of Thracians and their relations to contemporary Europeans. We conclude that contemporary Bulgarians do not harbor Thracian-specific ancestry, since ancient Thracian samples share more SNPs with contemporary Greeks and even contemporary Icelanders than with contemporary Bulgarians.


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