Evidence of prophylaxis treatment in adult haemophiliacs. Need of this treatment strategy?

In contrast to children with haemophilia the scientific evidence of prophylaxis treatment in adults is not yet proven. Existing studies are of observational character and mostly retrospectively designed. Therefore, opinion leaders in this field postulate prospectively designed, randomized, controlled and multicentric studies to set up urgently needed guidelines. Evidence according to the Canadian task force ranking is assessed as level III with a recommendation grade C by the authors. The recognition of benefits of health care providers in accordance with the German Federal Joint Committee generally demands a Grade-Ia to Ib evidence. As long as the actual evidence of prophylaxis in adult haemophiliacs does not meet the postulated criteria of the German Federal Joint Committee, prophylactic replacement therapy of the individual case has to be well documented and reasonably explained.

Persistence of effects of a brief intervention on parental restrictions of teen driving privileges.

OBJECTIVE: The purpose of this study was to determine the extent to which effects of exposure to a brief intervention designed to increase parental restrictions on teen driving privileges persisted over time. DESIGN: A total of 658 parents and their 16 year old adolescents were recruited from a local motor vehicle administration (MVA) site as adolescents successfully tested for provisional licenses. At the MVA, parents completed written surveys about expected teen driving during the first month of provisional licensure. Afterwards, on weeks assigned as intervention, parents watched a video and were given the video and a driving agreement to take home. Both parents and teens completed follow up telephone interviews about communication, amounts, and limits on teen driving at one month (579 dyads), four months (529 dyads), and nine months (528 dyads). RESULTS: The results indicated that both intervention parents and teens were much more likely to report using a driving agreement at each follow up during the nine month period. Significant treatment group differences persisted for communication about driving, but effects related to limits on teen driving that were evident at one month declined over time. Reports for passenger, road, and overall limits remained significant at four months; fewer were present at nine months. There were no differences in amounts of teen driving at four or nine months. CONCLUSIONS: It is possible to reach parents through brief interventions at the MVA and successfully promote increases in initial parental restrictions on teen driving with modest persistence for at least four months.

A comparison of teen perceptions and parental reports of influence on driving risk.

OBJECTIVES: To compare associations between teen and parent reports of parental driving influence to teen-reported high-risk driving. METHODS: A statewide sample of 424 Maryland parents and their provisionally licensed teenagers were interviewed. RESULTS: Reports of parental involvement with their driving to that of their parents indicated low levels of concordance. Teens who reported their parents had specific rules restricting who could ride with them as well as how many passengers were allowed to ride with them were less likely to report being distracted by friends, getting a ticket, driving too fast, or driving aggressively. CONCLUSION: Programs that enable parents to restrict and supervise their teen's driving, especially during the first 6 months of provisional licensure, are indicated.

Parental predictors of teen driving risk.

OBJECTIVES: To determine the nature and prevalence of parental involvement with teen driving and its relationship to teen driving risk. METHODS: A statewide sample of 424 Maryland parents and their provisionally licensed teenagers were interviewed. RESULTS: Parents were unaware of the extent to which their teens had engaged in high-risk traffic events, such as being distracted by friends or driving too fast. Teens who were allowed unsupervised access to a car at least several times a week were 3 times as likely to have driven too fast than were those who had access once a month or less. The frequency of parental teaching of driving skills was not strongly related to teen risk taking. CONCLUSION: The need to increase parents' capacity to impose and enforce driving restrictions on provisionally licensed teen drivers is indicated.

Associations between parent awareness, monitoring, enforcement and adolescent involvement with alcohol.

In a statewide random telephone survey of 454 parents and their 14- to 19-year-old adolescents, we examined the associations between various parenting strategies and self-reported teen drinking. Less teen drinking was associated with parents' reports of checking to see if other parents would be present at teen parties, particularly among White parents. Parents' monitoring of teens' activities was associated with feelings of competence at doing so. There was, however, no difference in drinking between teens with parents who did or did not report restricting their teens due to teen misbehavior. These findings suggest that a proactive parental monitoring approach may be associated with less adolescent drinking. Prospective research is needed to clarify the causal relationship between parental monitoring, efficacy and teen alcohol-related behavior.

Effects of ignition interlock license restrictions on drivers with multiple alcohol offenses: a randomized trial in Maryland.

OBJECTIVES: This investigation sought to test the effectiveness of a statewide ignition interlock license restriction program for drivers with multiple alcohol-related traffic offenses. METHODS: A total of 1387 multiple offenders eligible for license reinstatement were randomly assigned to participate in an ignition interlock program (experimental group) or in the conventional postlicensing treatment program (control group). The arrest rates of these 2 groups for alcohol traffic offenses were compared for 1 year during the ignition interlock license restriction program and for 1 year after unrestricted driving privileges were returned. RESULTS: Participation in the interlock program reduced offenders' risk of committing an alcohol traffic violation within the first year by about 65%. The alcohol traffic violation rate during the first year was significantly less for participants in the interlock program (2.4%) than for those in the control group (6.7%). However, there was no statistically significant difference between these groups in the second year, after the interlock license restriction was lifted. CONCLUSIONS: Ignition interlock license restriction programs are effective at reducing recidivism among drivers with multiple alcohol offenses, at least while the restriction is in effect.

Standardization of the PFA-100(R) platelet function test in 105 mmol/l buffered citrate: effect of gender, smoking, and oral contraceptives.

The PFA-100(R) (PFA) diagnostic system for the detection of platelet dysfunction was evaluated to determine reference ranges in a normal population. The PFA determines the primary haemostasis capacity (PHC) of anticoagulated whole blood, expressed by the system's closure time (CT). In this study the CT reference ranges were determined for blood samples collected in 105 mmol/l (3.2%) buffered citrate and the effect of gender, smoking, and use of oral contraceptives on reference ranges was assessed. Each of the 309 healthy blood donors from five blood centres was confirmed to have normal platelet function before inclusion in the study. Blood samples were tested in duplicate with both the collagen/epinephrine (Col/Epi) and collagen/ADP (Col/ADP) test cartridges. PFA reference ranges (90% central intervals of measured closure times) for both cartridge types were similar for all groups. Subgroup analysis showed that neither gender nor oral contraceptive usage had any effect on PHC. The 95% cut-off value for the Col/Epi CT was slightly higher for smokers than for non-smokers, an effect more pronounced in female than in male donors. However, the small difference did not justify establishment of specific reference ranges for smokers. Data from all included subjects were pooled to calculate the CT reference ranges for blood samples collected in 105 mmol/l buffered citrate (Col/Epi 82-150 s; Col/ADP 62-100 s). Normal levels of fibrinogen, as well as normal platelet counts and normal haematocrit levels, appeared not to influence the PHC. Because slight but significant differences of the reference ranges were observed between some of the participating sites, in-house confirmation of these reference range guidelines is recommended.

[Capture-R Ready-ID and DiaMed-ID for identification of erythrocyte bound antibodies after acid elution]. / Capture-R Ready-ID und DiaMed-ID zur Identifizierung erythrozytär gebundener Antikörper nach Säureelution.

The DiaMed-ID (D-ID) gel system is known to be a very sensitive and specific method for the detection of red cell antibodies. In various cases, we failed to find an antibody in the eluate in which red-cell-bound antibodies (IgG) where proven by a positive direct antiglobulin test (DAT). SPRCA (Capture-R, Ready Screen, Immucor; C-R) seems also to be very sensitive, in part due to the antihuman, IgG-coated indicator cells. Therefore, we compared 39 acid eluates from patients who had a positive DAT (monospecific rabbit antihuman IgG) both in the D-ID and in the C-R system. Patients (19 female, 20 male; mean age 62 years) were suspected either to have an autoimmune hemolytic anemia or an alloantibody. Identification of the antibodies was done with the system's own panel cells. Agglutination strength was scored from 1 to 4. Quantification of selected eluates was performed by titration, using the same cells in both systems. From 39 eluates, 31 were positive in the C-R and 25 in the D-ID. Nine eluates were negative in the C-R and 14 in the D-ID. If only eluates with a DAT reaction strength of 2 or lower were considered, obviously more negative results were found with the D-ID technique (p < 0.027) than with the C-R technique. In all eluates the degree of test reaction was stronger in the C-R system. However, titration endpoints of 6 quantified antibodies did not differ significantly. In 2 patients with slightly positive DAT, antibody typing was negative or not clear in the serum. In the corresponding eluates, an anti-K and an anti-JKa could be identified only by the C-R technique. In such instances we recommend to use the C-R technique to prevent transfusion complications.

Adolescent gender differences in alcohol problem behaviors and the social contexts of drinking.

This study of more than 1,300 high school students examined gender differences in the social context of drinking associated with four alcohol problem behaviors (high intensity drinking, binge drinking, driving while intoxicated, and riding with an alcohol impaired driver). A series of analyses treated five social contexts of drinking (Social Facilitation, School Defiance, Stress Control, Peer Acceptance, and Parental Approval) as dependent variables and revealed significant multivariate interaction effects between gender and all four alcohol problem behaviors. Male problem drinkers were more likely to drink in all social contexts than female problem drinkers or non-problem drinkers of both genders. Females were no more likely to drink in the context of Stress Control than males, a finding inconsistent with some previous research. The social contexts of Social Facilitation, School Defiance, and Stress Control were the best discriminators of problem versus non-problem drinkers of both genders (although the order of importance varied by gender and specific problem behavior). Implications for designing targeted interventions are discussed.

The relationship of social context of drinking, perceived social norms, and parental influence to various drinking patterns of adolescents.

An anonymous questionnaire was administered to a sample of over 890 adolescent drinkers. The questionnaire contained measures of their social context of drinking, perceived social norms, and perceived parental behaviors regarding drinking. These measures were related to a variety of alcohol problem behaviors including binge drinking, driving while alcohol-impaired, riding with an alcohol-impaired driver, and experiencing one or more negative consequences because of drinking. Results indicated that drinking frequently in a social context of social facilitation, stress control or school defiance, as well as having close friends engage in these behaviors, tended to separate alcohol abusers from nonabusers. The implications for program development are discussed.

[Advanced age--a risk factor in autologous blood donation?]. / Fortgeschrittenes Lebensalter--ein Risiko zur Eigenblutspende?

Tolerance of autologous blood donation was investigated in a patient group aged between 66 and 75 years (median = 70 years). Autologous blood donors between 18 and 65 years (median = 51 years) served as a control. A total of 38 patients were examined. Only blood donors which did not exceed ASA criteria II were accepted. Blood donation was performed weekly with a daily ferrum intake of 200 mg. Patients were divided into two groups with and without volume replacement, respectively. The parameters investigated were: blood pressure and pulse before and after the first and second autologous blood donation, circulatory response during 24 h after blood donation, and hemoglobin concentration before the first, second, and third donation. Regarding pulse and blood pressure, there was no statistical difference between the elder and younger patient group. Hemoglobin reduction from the first to the second donation was 1.1 g/dl in both groups and from the second to the third donation 1.1 g/dl in the younger group and 1.2 g/dl in the elder patient group. Again, no significant difference between both groups could be shown. None of the 38 patients showed negative side effects regarding the circulatory response during a time period of 24 h after blood donation.

Social context and sensation seeking: gender differences in college student drinking motivations.

An anonymous questionnaire was administered to students at two universities. The questionnaire contained the Social Context of Drinking Scales, the Sensation Seeking Scale, and measures of alcohol use intensity, frequency of alcohol-impaired driving, as well as frequency of riding with an impaired driver. The results revealed significant gender differences in the social context of drinking as well as sensation seeking. High intensity drinkers of each gender were more likely to drink in a context of Social Facilitation and score higher on the sensation seeking subscale--Disinhibition. High intensity men drinkers were more likely to drink in a context of Sex Seeking, whereas high intensity women drinkers tended to drink in a context of Emotional Pain. In general, the Social Context of Drinking Scales were superior to the Sensation Seeking Scales at being able to discriminate high from low intensity drinkers. The implications for targeted prevention programs on college campuses are discussed.

Desmopressin effect on acetylsalicylic acid impaired platelet function.

The mechanism of DDAVP's shortening of acetylsalicylic acid (ASA) prolonged bleeding times was investigated. Sixteen healthy subjects received two dosages of ASA (100 mg) in 12 hours. Twenty four hours after the first ASA application and again after 32 hours DDAVP was administered intravenously (0.4 micrograms/kg). The trial was terminated after 48 hrs. In between, blood samples were drawn and analyzed for the in vivo bleeding time (Simplate time), in vitro bleeding test (IVBT, Thrombostat 4000), von Willebrand factor antigen (vWf:Ag), Ristocetin cofactor activity (vWf R:Co), plasma beta-thromboglobulin (beta-TG), platelet ATP/ADP, platelet aggregation (collagen, ADP, arachidonic acid), and plasma and platelet thromboxane levels. Simplate time (BT) and IVBT showed an excellent inverse correlation with vWf R:Co (r2 BT = 0.97 and r2 IVBT = 0.99, respectively) during the time when DDAVP was administered, suggesting the involvement of plasma vWF in DDAVP's shortening of the bleeding time. The involvement of plasma thromboxane in this mechanism could be excluded. In addition, DDAVP hampered platelet aggregation tests, possibly due to the inhibition of the release reaction (reduced beta-TG in plasma) by a direct interaction with platelets.

DDAVP's shortening of the bleeding time seems due to plasma von Willebrand factor.

The pathomechanism of desmopressin (DDAVP) dependent shortening of the acetylsalicylic acid (ASA) prolonged bleeding time (BT) is still unclear. The mechanism of action is supposed to be related to the plasma levels of von Willebrand factor (vWf), but a platelet effect is also discussed. We tried to investigate whether this effect of DDAVP might be due to either plasma vWF or platelets or both. We measured the effect of DDAVP (0.4 micrograms/ml bw in 250 ml 0.9% NaCl) on the Thrombostat 4000 (in vitro bleeding test (IVBT)) after each of 16 volunteers ingested 100 mg of ASA twice. To measure the possible effect of DDAVP on plasma and platelets separately, a mixture of 800 microliters of platelet poor plasma (PPP) or 200 microliters of isolated platelets after DDAVP, respectively, was prepared and the IVBT monitored. Two hundred microliters of PPP or platelets, respectively, served as a control. In an additional experiment, vWF concentrate (12 U/ml) dissolved in 200 microliters of PPP after ASA ingestion, as described above, was added to 800 microliters of citrated whole blood from the same volunteers. The addition of PPP after DDAVP as well as the PPP or PRP after ASA enriched with vWf led to a significant shortening of the IVBT in comparison to the control, indicating that the effect of DDAVP on the prolonged BT seems to be an isolated effect of plasma vWf. By adding platelets we were not able to show a direct effect of DDAVP on platelets.

Social context, sensation seeking, and teen-age alcohol abuse.

An anonymous questionnaire was administered to more than 1,200 seventh to 12th grade students in four rural public schools in western New York State. The questionnaire measured alcohol use, the social contexts of drinking, and the personality trait known as "sensation seeking." A majority (57%) were drinkers, and discriminant function analyses were performed on their scores on these measures to determine if they could distinguish between different levels of alcohol use intensity, alcohol-impaired driving, and riding with an impaired driver. Results indicated social context measure were effective in distinguishing among levels on each indicant of abuse. In particular, high-intensity drinkers, impaired drivers, and riders of impaired drivers were more likely to drink in a context of social facilitation, stress control, and defiance of school and adult authority. The drinking context of peer acceptance was important only in distinguishing teen-agers who ride with drunk drivers from those who do not. Overall, the sensation seeking trait was of moderate importance in distinguishing among different alcohol abuse practices. Implications of these findings for assessment as well as school-based prevention programs are discussed.

Protocol and preliminary results of a clinical study for comparison of solvent/detergent-inactivated plasma VIP versus FFP with special consideration of the balance of hemostasis.

Solvent/detergent virus-inactivated plasma (VIP) contains markedly reduced protein S (PS) and alpha 2-antiplasmin (APL) beside other slightly decreased inhibitors. This could possibly be critical for the balance of hemostasis in diseases in which plasma inhibitors are reduced. A heterogeneous group of 14 patients with 18 plasma transfusions (12 FFP/24 VIP, 2 units per transfusion) was investigated. The patients suffered from dilution coagulopathy, liver disease, disseminated intravascular coagulation (DIC), hyperfibrinolysis, or received massive transfusions. Prothrombin fragment 1 + 2, fibrin monomers, D-Dimers, thrombin-AT III complexes, antiplasmin-plasmin complexes and fibrinogen degradation products as markers of activated coagulation (MAC) were measured. Blood samples were taken before and after plasma replacement. Significant differences between VIP and FFP should be recognized by comparing the ratio of MAC after/MAC before plasma transfusion. Patients showed an average inhibitor plasma level of AT III 51%, protein C 44%, PS 63%, and APL 52%. Only the F 1 + 2 ratio was obviously higher in the VIP group but not significantly. So the remaining MAC ratios did not show any significant difference. Our preliminary data showed no indication for a higher state of activation of coagulation in patients receiving VIP in comparison with those receiving FFP, if the VIP had the quality required. Solvent/detergent (SD) inactivation of transfusion-relevant viruses in plasma was successfully performed by Horowitz et al. [1]. The procedure leads to a partial reduction of the activity of clotting factors [2]. PS and APL are more severely affected. Therefore, treatment with VIP might activate or at least increase the activation of coagulation, especially in patients with reduced plasma inhibitors. To clarify this problem, the following disorders with the indication for plasma replacement were included in a prospective randomized study of FFP vs. VIP: massive transfusion; dilution coagulopathy; disturbance in liver synthesis; disseminated intravascular coagulation (DIC); primary hyperfibrinolysis. Low PS levels could induce hypercoagulability by reduced F VIII and FV inhibition, and low APL could induce hyperfibrinolysis by reduced plasmin inhibition.

[Vacuum ether elution--a modification of the Rubin ether elution method]. / Vakuum-Ather-Elution--eine Modifikation der Atherelutionsmethode nach Rubin.

The time-consuming ether elution of Rubin can be shortened by vacuum evaporation of the ether (< 10 min). The modification developed by us was compared with the conventional method investigating 103 blood samples with a positive direct antiglobulin test or a possible immunohemolysis. No significantly different results could be obtained with the two different elution methods.

[Preliminary results of a prospective randomized clinical study on the comparison of solvent- and detergent-inactivated plasma (SDP-TNBT/Triton X-100) and untreated fresh-frozen plasma]. / Erste Ergebnisse einer prospektiven randomisierten klinischen Studie zum Vergleich von Solvent-Detergent-inaktiviertem Plasma (SDP-TNBP/Triton X-100) und unbehandeltem Fresh-frozen-Plasma.

We report on preliminary results of a randomised clinical study comparing solvent/detergent-inactivated plasma to untreated FFP. Factors V, VII, VIII:C and protein S in the plasma units and in 14 patients were determined. Additionally, we measured prothrombin fragments 1,2, fibrin monomers, D-dimers, thrombin-antithrombin III, plasmin-antiplasmin complexes and fibrinogen degradation products as markers of activated coagulation (MAC), and calculated ratios of MACpost/ MACpre. One batch of SD plasma (SDP 797) with very high FVII and very low protein S seemed to produce significant changes in vivo without any clinical relevance. The bad quality of this batch could be due to virus inactivation in the early phase of large-scale routine production from a plasma pool that was too small.

[Shortening of acetylsalicylic acid-prolonged bleeding time by means of desmopressin]. / Verkürzung der durch Acetylsalicylsäure verlängerten Blutungszeit mittels Desmopressin.

The pathomechanism of desmopressin (DDAVP)-dependent shortening of the bleeding time prolonged by acetylsalicylic acid (ASA) was investigated by the Ivy bleeding time (BT) and the in vitro bleeding test (IVBT). Additionally, platelet aggregation and von Willebrand factor (vWF) were determined. The possible effect on plasma or platelets was examined by blood compositions containing citrated whole blood after ingestion of ASA plus either plasma or platelets after application of DDAVP (control: plasma or platelets after ASA). Excellent correlations were found between BT and IVBT as well as vWF (r2 = 0.97-0.99). In contrast, platelet aggregation decreased after administration of DDAVP. Experiments with blood compositions showed an effect of plasma and platelets as well in the IVBT after DDAVP administration. The results demonstrate the superiority of the IVBT to describe the in vivo function of platelets in comparison with the platelet aggregation test.