国際生活機能分類(International Classification of Functioning, Disability and Health: ICF)にみた福祉・保健・医療の専門職協働における連携に関する貢献と課題

Summary.  The gynaecological and obstetric management of women with inherited coagulation disorders requires close collaboration between obstetrician/gynaecologists and haematologists. Ideally these women should be managed in a joint disciplinary clinic where expertise and facilities are available to provide comprehensive assessment of the bleeding disorder and a combined plan of management. The haematologist should arrange and interpret laboratory tests and make provision for appropriate replacement therapy. These guidelines have been provided for healthcare professionals for information and guidance and it is also intended that they are readily available for women with bleeding disorders.

The obstetric and gynaecological management of woman with inherited bleeding disorders-review wit guidelinesproduced by a tasjforce of UK Hemophilia Centre Doctors' Organisation

糖尿病患者のHealth-Related Quality of Life(HRQOL)に関する心理学的研究

Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus 5 (AAV5)-based gene-therapy vector containing a coagulation factor VIII complementary DNA driven by a liver-selective promoter. The efficacy and safety of the therapy were previously evaluated in men with severe hemophilia A in a phase 1-2 dose-escalation study.We conducted an open-label, single-group, multicenter, phase 3 study to evaluate the efficacy and safety of valoctocogene roxaparvovec in men with severe hemophilia A, defined as a factor VIII level of 1 IU per deciliter or lower. Participants who were at least 18 years of age and did not have preexisting anti-AAV5 antibodies or a history of development of factor VIII inhibitors and who had been receiving prophylaxis with factor VIII concentrate received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight. The primary end point was the change from baseline in factor VIII activity (measured with a chromogenic substrate assay) during weeks 49 through 52 after infusion. Secondary end points included the change in annualized factor VIII concentrate use and bleeding rates. Safety was assessed as adverse events and laboratory test results.Overall, 134 participants received an infusion and completed more than 51 weeks of follow-up. Among the 132 human immunodeficiency virus-negative participants, the mean factor VIII activity level at weeks 49 through 52 had increased by 41.9 IU per deciliter (95% confidence interval [CI], 34.1 to 49.7; P<0.001; median change, 22.9 IU per deciliter; interquartile range, 10.9 to 61.3). Among the 112 participants enrolled from a prospective noninterventional study, the mean annualized rates of factor VIII concentrate use and treated bleeding after week 4 had decreased after infusion by 98.6% and 83.8%, respectively (P<0.001 for both comparisons). All the participants had at least one adverse event; 22 of 134 (16.4%) reported serious adverse events. Elevations in alanine aminotransferase levels occurred in 115 of 134 participants (85.8%) and were managed with immune suppressants. The other most common adverse events were headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%). No development of factor VIII inhibitors or thrombosis occurred in any of the participants.In patients with severe hemophilia A, valoctocogene roxaparvovec treatment provided endogenous factor VIII production and significantly reduced bleeding and factor VIII concentrate use relative to factor VIII prophylaxis. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.). 

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Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A

BACKGROUND
Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus 5 (AAV5)-based gene-therapy vector containing a coagulation factor VIII complementary DNA driven by a liver-selective promoter. The efficacy and safety of the therapy were previously evaluated in men with severe hemophilia A in a phase 1-2 dose-escalation study.


METHODS
We conducted an open-label, single-group, multicenter, phase 3 study to evaluate the efficacy and safety of valoctocogene roxaparvovec in men with severe hemophilia A, defined as a factor VIII level of 1 IU per deciliter or lower. Participants who were at least 18 years of age and did not have preexisting anti-AAV5 antibodies or a history of development of factor VIII inhibitors and who had been receiving prophylaxis with factor VIII concentrate received a single infusion of 6×1013 vector genomes of valoctocogene roxaparvovec per kilogram of body weight. The primary end point was the change from baseline in factor VIII activity (measured with a chromogenic substrate assay) during weeks 49 through 52 after infusion. Secondary end points included the change in annualized factor VIII concentrate use and bleeding rates. Safety was assessed as adverse events and laboratory test results.


RESULTS
Overall, 134 participants received an infusion and completed more than 51 weeks of follow-up. Among the 132 human immunodeficiency virus-negative participants, the mean factor VIII activity level at weeks 49 through 52 had increased by 41.9 IU per deciliter (95% confidence interval [CI], 34.1 to 49.7; P<0.001; median change, 22.9 IU per deciliter; interquartile range, 10.9 to 61.3). Among the 112 participants enrolled from a prospective noninterventional study, the mean annualized rates of factor VIII concentrate use and treated bleeding after week 4 had decreased after infusion by 98.6% and 83.8%, respectively (P<0.001 for both comparisons). All the participants had at least one adverse event; 22 of 134 (16.4%) reported serious adverse events. Elevations in alanine aminotransferase levels occurred in 115 of 134 participants (85.8%) and were managed with immune suppressants. The other most common adverse events were headache (38.1%), nausea (37.3%), and elevations in aspartate aminotransferase levels (35.1%). No development of factor VIII inhibitors or thrombosis occurred in any of the participants.


CONCLUSIONS
In patients with severe hemophilia A, valoctocogene roxaparvovec treatment provided endogenous factor VIII production and significantly reduced bleeding and factor VIII concentrate use relative to factor VIII prophylaxis. (Funded by BioMarin Pharmaceutical; GENEr8-1 ClinicalTrials.gov number, NCT03370913.).

Valoctocogene Roxaparvovec Gene Therapy for Hemophilia A.

WFH Guidelines for the Management of Hemophilia, 3rd edition

Introduction There is significant incidence of Haemophilia in India, with second largest number of persons with Haemophilia A. 20,778 patients registered with Haemophilia Foundation of India in 2018. Research in India includes diagnostic studies, complications and co-morbidities, prenatal diagnosis, inhibitor development and gene therapy. Limited is known about quality of life of these patients. Since Haemophilia leads to the loss of 'normal lifestyle' in young people resulting in emotional distress and depression, it is important to analyse Knowledge, Attitude and Behaviour of persons with Haemophilia. Aim The aim of the study is to focus on exploring the status of Haemophilia and knowledge, attitude, behaviour of adolescents and youths with haemophilia with the objectives to study 1) the current medical status of haemophilia amongst target population; 2) the knowledge, attitude and behaviour of patients with haemophilia towards their condition. Methods Respondents in the age group of 15-30 years, who were registered with the Hemophilia Treatment Centers of Government Hospitals/Hemophilia Societies, were interviewed. Data were collected using a structured questionnaire. The study was conducted in two different states and with respondents of two different age groups. Findings Most respondents suffered from severe haemophilia and co-morbidities such as anxiety, stress, chronic pain and head-ache. All of them felt that haemophilia interferes in leading a normal life and perceive a grim future. Conclusion Young people in India need technical, financial and psychological support to prevent complications related to haemophilia. While most of them take responsibility for their health, more behavioural changes need to be inducted to improve quality of life.

Richa Mohan

Papers

WFH Guidelines for the Management of Hemophilia, 3rd edition

Assessing the current knowledge, attitude and behaviour of adolescents and young adults living with haemophilia