Современные представления о супружеских конфликтах и супружеской дезадаптации

Рассмотрены современные данные о семейных конфликтах и связанной с ними супружеской дезадаптации. Сделан вывод о необходимости дальнейшей разработки этой проблемы.Modern data about family conflicts and the associated spouse deadaptation are discussed. The author concludes about the necessity of further investigation of the issue

The Forms of Action at Common Law

xi, 75 hal.; 22 c

Early HTA in pharmacogenomics : A case example in cardiovascular drugs

Objectives: ACE inhibitors (ACEi) are commonly used cardiovascular drugs. These drugs can cause the severe and possibly lethal adverse drug reaction (ADR) angioedema in a very small part (0.2%) of the patients. A pharmacogenomic test could be used to identify patients at risk for this severe ADR and advise them to use another drug. The goal of this study is to assess the test characteristics (cost, sensitivity and specificity) in order for it to be a cost effective test for preventing ACEi-induced angioedema. Furthermore, we assessed the influence of only testing part of the population carrying risk factors for angioedema. Methods: A decision tree was used as angioedema usually occurs within the first year after starting an ACEi and data on long term risk is scarce. Test characteristics were assessed using Monte Carlo simulation. Results: With a willingness-to-pay (WTP) threshold of € 20,000 and € 80,000 per QALY, a 100% sensitive and specific test may have a maximum cost of € 1.29 and € 1.92, respectively. A decrease in specificity has a 10-fold higher impact on the ICER than sensitivity as additional drug costs of false positives rapidly overcome the benefit of preventing angioedema. In order to warrant a € 1.00 test price, specificity needs to be > 95% whilst sensitivity may drop to 70% provided that specificity remains > 98%. African people have a 3.88 times higher risk of developing angioedema than Caucasian people. When only genotyping this population, the maximum test price (100% sensitive and specific) would be € 3.21 and € 5.67 at a WTP threshold of € 20,000 and € 80,000, respectively. Conclusions: A theoretical pharmacogenomic test for ACEi-induced angioedema is only cost-effective at very high specificity, decent sensitivity and a low price. If only used in patients with a high risk on angioedema, the maximum test price could increase to a somewhat more realistic 5 Euro figure

Early HTA in pharmacogenomics : A case example in cardiovascular drugs

Objectives: ACE inhibitors (ACEi) are commonly used cardiovascular drugs. These drugs can cause the severe and possibly lethal adverse drug reaction (ADR) angioedema in a very small part (0.2%) of the patients. A pharmacogenomic test could be used to identify patients at risk for this severe ADR and advise them to use another drug. The goal of this study is to assess the test characteristics (cost, sensitivity and specificity) in order for it to be a cost effective test for preventing ACEi-induced angioedema. Furthermore, we assessed the influence of only testing part of the population carrying risk factors for angioedema. Methods: A decision tree was used as angioedema usually occurs within the first year after starting an ACEi and data on long term risk is scarce. Test characteristics were assessed using Monte Carlo simulation. Results: With a willingness-to-pay (WTP) threshold of € 20,000 and € 80,000 per QALY, a 100% sensitive and specific test may have a maximum cost of € 1.29 and € 1.92, respectively. A decrease in specificity has a 10-fold higher impact on the ICER than sensitivity as additional drug costs of false positives rapidly overcome the benefit of preventing angioedema. In order to warrant a € 1.00 test price, specificity needs to be > 95% whilst sensitivity may drop to 70% provided that specificity remains > 98%. African people have a 3.88 times higher risk of developing angioedema than Caucasian people. When only genotyping this population, the maximum test price (100% sensitive and specific) would be € 3.21 and € 5.67 at a WTP threshold of € 20,000 and € 80,000, respectively. Conclusions: A theoretical pharmacogenomic test for ACEi-induced angioedema is only cost-effective at very high specificity, decent sensitivity and a low price. If only used in patients with a high risk on angioedema, the maximum test price could increase to a somewhat more realistic 5 Euro figure

Associations of comorbidities and co-medications with angioedema during the use of angiotensin converting enzyme-inhibitors within the United Kingdom clinical practice research Datalink

Objectives: This study describes the occurrence of angioedema among patients initiating ACEI therapy and evaluates the association of this outcome with demographic factors, co-medication and chronic comorbidities. Methods: A nested case-control study was conducted in a cohort of patients newly treated with ACEIs from 2007 to 2014 in the CPRD. Cases who had angioedema only during ACEI treatment were identified using medical codes and were matched on the duration of ACEI treatment at the angioedema date (index date) with up to 20 controls who never had angioedema recorded. The use of co-medication (anti-diabetics, antihistamines, anti-asthmatics, non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, calcium channel blockers and statins), was acquired from CPRD prescription records within a three months' time window before the index date. The history of comorbidities (asthma, allergy, chronic obstructive pulmonary disease (COPD), diabetes mellitus and rheumatoid arthritis) was retrieved from medical records any time before the index date. Odds ratios (ORs) and p-values were estimated using univariate logistic regression analysis. Results: The cohort included 276,977 patients aged ≥ 45 years initiating ACEI therapy. The study population included 416 cases of angioedema during ACEI therapy matched with 4,335 controls. Age over 65 years was associated with angioedema. The proportions of asthma, allergy, COPD and rheumatoid arthritis were significantly higher in ACEI consumers who developed angioedema during ACEI therapy (ORs 1.83, 2.03, 2.08 and 2.83 respectively; p<0.001), compared to controls. History of diabetes and use of anti-diabetic drugs were associated with a decreased risk for angioedema (OR 0.73, P= 0.034). Antihistamines, anti-asthmatic drugs and systemic corticosteroids were associated with angioedema during ACEI therapy (ORs 25.64, 2.19 and 7.15 respectively; p<0.001). Conclusions: Angioedema during ACEI therapy was more frequent in patients over 65 years old and in patients with history of inflammatory comorbidities, such as asthma and allergies

Associations of comorbidities and co-medications with angioedema during the use of angiotensin converting enzyme-inhibitors within the United Kingdom clinical practice research Datalink

Objectives: This study describes the occurrence of angioedema among patients initiating ACEI therapy and evaluates the association of this outcome with demographic factors, co-medication and chronic comorbidities. Methods: A nested case-control study was conducted in a cohort of patients newly treated with ACEIs from 2007 to 2014 in the CPRD. Cases who had angioedema only during ACEI treatment were identified using medical codes and were matched on the duration of ACEI treatment at the angioedema date (index date) with up to 20 controls who never had angioedema recorded. The use of co-medication (anti-diabetics, antihistamines, anti-asthmatics, non-steroidal anti-inflammatory drugs (NSAIDs), systemic corticosteroids, calcium channel blockers and statins), was acquired from CPRD prescription records within a three months' time window before the index date. The history of comorbidities (asthma, allergy, chronic obstructive pulmonary disease (COPD), diabetes mellitus and rheumatoid arthritis) was retrieved from medical records any time before the index date. Odds ratios (ORs) and p-values were estimated using univariate logistic regression analysis. Results: The cohort included 276,977 patients aged ≥ 45 years initiating ACEI therapy. The study population included 416 cases of angioedema during ACEI therapy matched with 4,335 controls. Age over 65 years was associated with angioedema. The proportions of asthma, allergy, COPD and rheumatoid arthritis were significantly higher in ACEI consumers who developed angioedema during ACEI therapy (ORs 1.83, 2.03, 2.08 and 2.83 respectively; p<0.001), compared to controls. History of diabetes and use of anti-diabetic drugs were associated with a decreased risk for angioedema (OR 0.73, P= 0.034). Antihistamines, anti-asthmatic drugs and systemic corticosteroids were associated with angioedema during ACEI therapy (ORs 25.64, 2.19 and 7.15 respectively; p<0.001). Conclusions: Angioedema during ACEI therapy was more frequent in patients over 65 years old and in patients with history of inflammatory comorbidities, such as asthma and allergies