Secondary prophylaxis with recombinant activated factor VII improves health-related quality of life of haemophilia patients with inhibitors.

Haemophilia patients with inhibitors characteristically have impaired joint function and reduced health-related quality of life (HRQoL). This analysis examined whether secondary prophylaxis with recombinant activated factor VII (rFVIIa) improves HRQoL vs. conventional on-demand therapy in patients with haemophilia with inhibitors and frequent bleeds. After a 3-month preprophylaxis period, 22 patients received daily rFVIIa prophylaxis (90 or 270 microg kg(-1)) for 3 months, followed by 3 months' postprophylaxis. Days of hospitalization, absence from school/work and mobility aids requirements were recorded. HRQoL was assessed by EuroQoL (EQ-5D) questionnaire, visual analogue scale (VAS), derived Time to Trade-Off (TTO) scores and Quality Adjusted Life Years (QALYs). rFVIIa prophylaxis significantly (P < 0.0001) reduced bleeding frequency vs. prior on-demand therapy. Hospitalization (5.9% vs. 13.5%; P = 0.0026) and absenteeism from school/work (16.7% vs. 38.7%; P = 0.0127) decreased during prophylaxis; these effects tended to be maintained during postprophylaxis. HRQoL (evaluated by EQ-5D) tended to improve during and after rFVIIa prophylaxis. Notably, pain decreased and mobility increased in 40.9% and 27.3% of patients, respectively, at the end of the postprophylaxis period vs. preprophylaxis. Median VAS score increased from 66 to 73 (P = 0.048), and TTO scores suggested better HRQoL (0.62 vs. 0.76; P = 0.054) during postprophylaxis than preprophylaxis. Small to moderate changes in effect sizes were reported for VAS and TTO scores. Median QALYs were 0.68 (VAS) and 0.73 (TTO). Reductions in bleeding frequency with secondary rFVIIa prophylaxis were associated with improved HRQoL vs. on-demand therapy.

Randomized, prospective clinical trial of recombinant factor VIIa for secondary prophylaxis in hemophilia patients with inhibitors.

BACKGROUND: Hemophilic patients with factor VIII (FVIII) and FIX inhibitors suffer from frequent bleeding episodes and reduced quality of life. OBJECTIVES: To evaluate whether secondary prophylaxis with activated recombinant factor VII (rFVIIa) can safely and effectively reduce bleeding frequency as compared to conventional on-demand therapy. METHODS: Thirty-eight male patients entered a 3-month preprophylaxis period to confirm high baseline bleeding frequency (mean > or = 4 bleeds per month). Twenty-two patients were randomized 1:1 to receive daily rFVIIa prophylaxis with either 90 or 270 microg kg(-1) for 3 months, followed by a 3-month postprophylaxis period. RESULTS: Bleeding frequency was reduced by 45% and 59% during prophylaxis with 90 and 270 microg kg(-1), respectively (P < 0.0001); however, there was no significant difference detected between doses. The majority of this reduction was maintained during the postprophylaxis period. Although all types of bleed were similarly reduced, the effect was most pronounced for spontaneous joint bleeds. Patients reported significantly fewer hospital admissions and days absent from work/school during prophylaxis as compared to the preprophylaxis period. No thromboembolic events were reported during prophylaxis. CONCLUSION: Clinically relevant reductions in bleeding frequency during prophylaxis as compared to conventional on-demand therapy were achieved without raising safety concerns. These results provide evidence for the concept of secondary rFVIIa prophylaxis in inhibitor patients with frequent bleeds.

Hyperhomocysteinemia, thrombosis and vascular biology.

Epidemiological evidence suggests that hyperhomocysteinemia (HH) is an independent risk factor for arterial thrombotic diseases such as acute myocardial infarction, stroke, peripheral ischemic occlusive disorders as well as venous thromboembolism. This article presents a hypothesis to explain the pathogenesis of increases in plasma homocysteine level and associated increased risk of thrombotic disease. It is based on the data in the literature and results from our laboratory on the impact of folate induced HH in rats. These results include: a) Effects on whole blood coagulation, which is characterized by increased velocity of coagulation, increased firmness of the formed coagulum and prolonged initiation phase of the coagulation; b) Genetic regulation of blood cells, which is characterized by increased platelet activation, impaired fibrinolysis and impaired function of the contact activation pathway of coagulation, and c) Reduced functional activities of single coagulation factors FXII:C, FX:C and FII:C.

The Saskatchewan dissemination story.

The Saskatchewan Heart Health Program (SHHP) Dissemination Phase "Building Health Promotion Capacity" is a five-year program funded by Health Canada, Saskatchewan Health and the Heart and Stroke Foundation of Saskatchewan. This phase began in July 1998 and builds on two previous SHHP phases: the provincial heart health survey (Saskatchewan Health, 1990), and the community demonstration projects (SHHP, 1998a, b, c, d). The evolution of the SHHP has occurred in a dynamic provincial context. Saskatchewan is a Canadian prairie province of one million people with most living in the southern and central parts of the province. The population is ageing and urbanizing, and the economy is shifting away from agricultural production toward a diversified service sector. In 1993, health reform created 30 Districts in southern and central Saskatchewan; the formation of three northern Districts followed five years later. All but two Districts are rural-based. Population served ranges from 2,261 to 237,274; total area ranges from 4,019 to 133,900 square kilometers.

Leukocyte-depletion of blood components does not significantly reduce the risk of infectious complications. Results of a double-blinded, randomized study.

Allogeneic blood transfusions are claimed to be an independent risk factor for postoperative infections in open colorectal surgery due to immunomodulation. Leukocyte-depletion of erythrocyte suspensions has been shown in some open randomized studies to reduce the rate of postoperative infection to levels observed in nontransfused patients. Using a double-blinded, randomized design, we studied the postoperative infection rate in patients undergoing open colorectal surgery transfused with either leukocyte-depleted erythrocyte suspensions (LD-SAGM) or non-leukocyte-depleted erythrocyte suspensions (SAGM). Unselected patients (n 279) were allocated to receive LD-SAGM (n 139) or SAGM (n 140) if transfusion was indicated. Forty-five percent were transfused, yielding 48 patients in the LD-SAGM group and 64 in the SAGM group. Thirteen patients were excluded because they received one type of transfusion in spite of randomization to the other type. No significant differences in the rates of postoperative infections (P=0.5250) or postoperative complications (P=0.1779) were seen between the two transfused groups. Infection rates were 45% and 38% in the transfused groups and 21% and 23% in the nontransfused groups. No significant difference between the transfused groups was seen on any single infectious event, mortality rate, or duration of hospitalization. Leukocyte-depletion of erythrocyte suspensions transfused to patients undergoing open colorectal surgery does not reduce postoperative infection rates.

Heart health in rural Saskatchewan.

In Saskatchewan, as in the rest of Canada, cardiovascular disease (CVD) is the leading cause of death and hospitalization. Indeed, the rate of decline in mortality has been slower in Saskatchewan than in most other provinces. So when the federal-provincial Canadian Heart Health Initiative was established in 1986, the province set up the Saskatchewan Heart Health Program both to form part of the national initiative and to take advantage of the opportunities implicit in it.

Anxiety and depression after acute myocardial infarction.

OBJECTIVES: To assess the following: (1) symptoms of anxiety and depression in hospitalized patients who had acute myocardial infarction (AMI); (2) the association between sex, infarct severity, history of previous AMI, and symptoms of anxiety and depression in hospitalized patients; (3) symptoms of anxiety and depression during the first year after AMI in a select group of patients; and (4) the association between educational and occupational status and symptoms of anxiety and depression at the time of hospitalization in a select group of patients. DESIGN: Cross-sectional survey (objectives 1 and 2) and prospective trial with random assignment (objectives 3 and 4). SETTING: Six university-affiliated hospitals in a Canadian city. PATIENTS: Seven hundred eighty-five hospitalized patients with AMI, with 1-year follow-up of 201 selected patients from this sample. INSTRUMENTS: State-Trait Anxiety Inventory and the short form of the Beck Depression Inventory. INTERVENTION: Data collection was initiated in the hospital 3 days after AMI, and patients were followed-up 14, 24, 41, and 56 weeks after AMI. RESULTS: Student t tests, analysis of variance, and descriptive statistics were used. When the patients were in the hospital the mean state (S-anxiety) and trait (T-anxiety) scores were 43 and 44, respectively. Ten percent had S-anxiety scores and 14% had T-anxiety scores that were higher than the mean scores reported for psychiatric patients. During the 1-year follow-up in the select group of subjects, the mean S-anxiety and T-anxiety scores were both 48 in-hospital, and decreased to 42 and 46, respectively, by 14 weeks and remained at these levels for the remainder of the year. During the course of the year, 16% of the patients had State-Trait Anxiety Inventory scores consistent with psychiatric conditions. The in-hospital Beck Depression Inventory mean score was 3, and 9% of the patients had scores consistent with moderate to severe depression. During the first 24 weeks, symptoms of moderate to severe depression were reported by 10% of the select group of patients. No associations were found between anxiety and depression and sex, creatine phosphokinase level, previous AMI, education, or occupational status. CONCLUSIONS: Symptoms of anxiety were prevalent among hospitalized patients who had an AMI, whereas depressive symptoms were rare. There was no association between anxiety and depression and sex, infarct severity, history of previous AMI, or educational or occupational status.

Measuring quality of life in cardiac spouses.

The purpose of this study was to develop an objective instrument to measure changes in quality of life of spouses of post-myocardial infarction (MI) patients, and to determine its responsiveness and validity. A 70-item list of potential areas of concern was compiled; the 25 most frequent and important concerns comprised the framework of the final questionnaire. The questions on the Quality of Life Questionnaire for Cardiac Spouses (QL-SP) were categorized into the Emotional Function Dimension (EFD), and the Physical and Social Function Dimension (PSFD). Subjects (n = 39) completed the QL-SP and a battery of established questionnaires at home, 1-2 weeks post-hospital discharge for the patient, and 8 weeks later. Scores on the QL-SP between visits were improved for both the EFD (t = 5.56, p less than 0.001), and the PSFD (t = 6.11, p less than 0.001). The agreement between predicted and observed relationships between the dimension changes and other index changes, as measured statistically by a kappa with Cicchetti weights, was significant (kappa w = 0.43, p = 0.0012). The QL-SP appears to be responsive and valid, and may be useful in evaluating clinical and research intervention strategies.