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Reflections on the Lack of Consideration of Ethnic Ancestry to Stratify Clozapine Dosing
Jose de Leon(Jose de Leon ) 대한신경정신의학회 2023 PSYCHIATRY INVESTIGATION Vol.20 No.3
This review article argues against trusting standard clozapine references, including the US package insert, because they do not include advances in the sciences of pharmacokinetics and pharmacovigilance and ignore the effects of ethnic ancestry on therapeutic dosing. The minimum therapeutic dose leading to the minimum therapeutic concentration of 350 ng/mL in serum/plasma can be used to compare individuals/groups with treatment-resistant schizophrenia. The US clozapine package insert recommends targeting doses of 300-450 mg/day and, subsequently, increments of up to 100 mg with a maximum dose of 900 mg/day. Ethnic ancestry is defined by DNA ancestry group. Asians (people with ancestry ranging from Pakistan to Japan) and Indigenous Americans are similar in clozapine dosing; their average clozapine minimum therapeutic dose ranged from 166 mg/day (female non-smokers) to 270 mg/day (male smokers). For those with European ancestry, average clozapine minimum therapeutic doses ranged from 236 mg/day (female non-smokers) to 368 mg/day (male smokers). Based on limited studies, Black (African sub-Saharan ancestry) patients may be treated with typical US doses (300-600 mg/day), assuming no poor metabolism (PM) status. Ancestry’s impact on clozapine lethality in four countries is discussed (two countries with highly homogenous populations, Denmark and Japan, and two countries with increasingly heterogenous populations due to immigration, Australia and the UK). An international guideline with 104 authors from 50 countries/regions was recently published, providing 6 personalized clozapine titration schedules for adult inpatients (3 ancestry groups and PM/non-PM schedules) and recommending c-reactive protein monitoring at baseline and weekly for 4 weeks.
Situational Philosophy : Towards a theory of philosophical practice
( Leon De Haas ) 한국철학상담치료학회 2012 철학 실천과 상담 Vol.3 No.-
This essay is a revised and expanded version of the text which was the basis for the author’s Masterclass at the 11th International Conference on Philosophical Practice (ICPP), the 18th of July 2012 at the Humanities Institute, Kangwon National University in Chuncheon, Republic of Korea. The main goal of the essay is, to contribute to a theory of philosophical practice. To do this, the author develops a criticism of reductionist practices in philosophy. The theoretical point of departure is an abridged survey of the two paradigmatic changes in European philosophy in the 20th century, i.e., Husserl’s phenomenology, and Wittgenstein’s language game analysis. The line of thinking is illustrated by a case story of the author. Part I discusses the phenomenological and linguistic turns in European philosophy. Part II describes and discusses a case story. Part III criticizes two forms of reductionism in philosophical practice, namely psychological and conceptual reductionism. Part IV gives an initial impetus to a theory of philosophical practice beyond any reductionism. In the present essay, the author is dealing with Western philosophy only, as the origins of post-Modern philosophical practice are rooted in Western philosophy. Lately, Eastern philosophy has been an inspiration for philosophical practice as well.
Political Prospects for a NWFZ in Northeast Asia
Leon V. Sigal 인하대학교 국제관계연구소 2011 Pacific Focus Vol.26 No.1
A Northeast Asian Nuclear Weapons Free Zone (NWFZ) or a Japan-South Korea NWFZ could entice the DPRK to carry out its commitment in the September 2005 Six-Party Joint Statement to “abandoning all nuclear weapons and existing nuclear programs”. In two possible scenarios for the nuclear future of North Korea, and in turn, the security of South Korea and Northeast Asia: containment, in which North Korea remains nuclear-armed with a growing stockpile of nuclear weapons and gradually improving delivery capabilities, and gradual rapprochement with the United States, South Korea, and Japan, a Northeast Asian NWFZ or a Japan-South Korea NWFZ would improve prospects for regional stability and a denuclearized Korean peninsula and could make a significant impact in light of North Korea’s nuclear arming and other recent changes in the security environment in the region and has implications for the future role of nuclear weapons in the regional balance of power.