A prospective controlled trial comparing weekly self-testing and self-dosing with the standard management of patients on stable oral anticoagulation.

Oral anticoagulant therapy requires frequent laboratory controls of its intensity to assure therapeutic efficacy and to prevent potentially life threatening adverse events. It is generally assumed, that increasing the frequency of testing would lead to a better control of anticoagulation. We tested this hypothesis in a prospective controlled trial comparing weekly self-testing and self-dosing (self management) with the standard-management of these patients in an anticoagulation clinic. Only patients with stable anticoagulation were included into the study. We recorded 2733 weekly determinations of the intensity of anticoagulation (INR) in 49 patients on self-testing and self-dosing and 539 determinations of the INR in 53 patients on standard-management. Two intensities of anticoagulation were used in each group: a target INR of 3.5 for patients with artificial heart valves (target range: 2.5-4.5) and a target INR 2.5 (target range: 2.0-3.0) for patients with atrial fibrillation or venous thromboembolism. The deviation from the target INR, the fraction of INR determinations within the preset therapeutic range and the difference between the target INR and the actually achieved mean INR were the three major endpoints of the study. The mean deviation from the target INR was smaller in the groups of patients on self-management compared to the patients on standard-management. Individual deviations were significantly (p <0.0001) dependent on the type of management in interaction with the treatment intensity in a general linear model. Patients on weekly self-testing and self-dosing had more INR values within the therapeutic range than patients on standard-management (86.2% vs. 80.1% at INR range 2.5-4.5; 82.2 vs. 68.9 at INR range 2.0-3.0). The achieved mean INR was almost identical with the target INR in the patients on self-management but was significantly (p <0.005) below the target INR in the high intensity anticoagulation group on standard-management (target INR:3.5; achieved mean INR: 3.19; CI 0.95: 3.05-3.34). Our data show, that weekly self-testing and self-dosing leads to a better control of anticoagulation than standard treatment in an anticoagulation clinic.

Long-term disorders of the blood-aqueous barrier after small-incision cataract surgery.

PURPOSE: To determine the long-term function of the blood-aqueous barrier after small-incision cataract surgery with implantation of a foldable intraocular lens. METHODS: The blood-aqueous barrier function in 74 eyes of 62 patients who underwent cataract surgery was examined using a laser flare-cell meter. The measurements were performed pre-operatively and post-operatively between 12 and 35 months after surgery. For statistical analysis a linear regression was used. The study was designed as a single cohort study, with comparison of pre- and post-operative values. RESULTS: Highly statistically significant differences (p < 0.0001) were found between pre-operative flare values and those measured at the final visit. The linear regression model showed significantly higher flare values post-operatively compared with those measured pre-operatively. Other variables such as incision technique, sex, operation time, phaco time and systemic disease had no influence on this outcome. CONCLUSION: The results suggest that there is persistent blood-aqueous barrier dysregulation even several years after cataract surgery.

Statistical quality control in clinical trials.

We propose to apply statistical methods of industrial process and quality control to accumulating data in a statistical monitoring center of a clinical trial. We discuss some specific issues connected with the application of these methods over calendar time to patients' characteristics (at a particular individual patient time) or to more formal monitoring characteristics (like the number of queries per case record form). The tools used are Shewart charts, plots, breakpoint regression, and recursive residuals with cusums and V-charts, applied to measurement and event data. A software program based on SAS macros allows easy application of the methods. Some examples, with graphical outputs, from an ongoing trial on patients with primary malignant melanoma, illustrate the methods.

Immunoglobulin administration to fetuses with anemia due to alloimmunization to D.

BACKGROUND: The purpose of this study was to examine fetal tolerance of high-dose intravenous immunoglobulin (IVIG), given directly at the time of intravascular transfusion, and its effects on fetal hemolysis and pregnancy outcome in the setting of alloimmunization to D. STUDY DESIGN AND METHODS: Thirteen consecutive D+ fetuses requiring transfusion for maternal alloimmunization received high-dose IVIG (1.0 g/kg) and red cell transfusions. Twenty-four previous, consecutive fetuses with maternal anti-D served as controls. The schedules for subsequent transfusions were the same in the two groups. RESULTS: High-dose IVIG was well tolerated by all fetuses. In the IVIG group, daily decreases in hematocrit were smaller than those in controls after the second administration of IVIG (mean hematocrit decrease, 0.72 percent/day vs. 1.45 percent/day; p = 0.007). No significant difference was found in the total number of fetal transfusions, the gestational age at delivery, the duration of neonatal intensive care, the number of neonates requiring postnatal transfusion therapy, and perinatal mortality. CONCLUSION: In this small pilot study, direct administration to fetuses of IVIG with red cell transfusions was well tolerated and appeared to have a beneficial effect on fetal hemolysis.

The impact of urinary extravasation after radical retropubic prostatectomy on urinary incontinence and anastomotic strictures.

OBJECTIVE: The aim of this study was to determine the relevance of urinary extravasation as proven by cystogram 18 days after radical retropubic prostatectomy for the degree of postoperative urinary incontinence and the incidence of anastomotic strictures. PATIENTS AND METHODS: A total of 225 patients underwent radical retropubic prostatectomy at our institution during a 30-month period, 215 of whom received a cystogram a mean 18 days following surgery. Three and 6 months after surgery these 215 patients were evaluated regarding the degree of urinary incontinence and the presence of anastomotic strictures. RESULTS: The cystogram demonstrated a watertight anastomosis in 89% (n = 195; group I), the remaining 11% (n = 24; group II) showed urine extravasation. Groups I and II were comparable with respect to age, preoperative serum levels of prostate-specific antigen (PSA), tumor grade and pathological staging. Six months after surgery, there was no statistically significant (p > 0.05) difference between both groups regarding the degree of urinary incontinence and the presence of anastomotic strictures. CONCLUSIONS: The presence of urine extravasation 18 days after radical retropubic prostatectomy has no impact on postoperative urinary incontinence and the incidence of anastomotic strictures. Based on these data it is not indicated to leave the catheter in situ beyond that point of time.

Course of postoperative inflammation after implantation of 4 types of foldable intraocular lenses.

PURPOSE: To compare the course of postoperative inflammation after small incision cataract surgery with implantation of 4 types of foldable intraocular lenses (IOLs). SETTING: Department of Ophthalmology, University Hospital of Vienna, Austria. METHODS: One hundred twenty eyes were prospectively randomized to receive a foldable silicone (Pharmacia 920), hydrogel (Bausch & Lomb Hydroview), methyl methacrylate/hydroxyethyl methacrylate (Mentor MemoryLens), or acrylic (Alcon AcrySof) IOL. All surgery was performed by the same experienced surgeon using a standardized surgical protocol: clear corneal incision, capsulorhexis, phacoemulsification, and in-the-bag implantation of the IOL. All patients received standardized postoperative medication and follow-up. Postoperative inflammation was evaluated by measuring aqueous flare preoperatively and 1, 3, 7, 14, 28, 90, and 180 days after surgery using the Kowa 1000 laser flare-cell meter. RESULTS: Except on the first day after surgery, when the AcrySof group had higher flare values than the other groups (P = .0265), no significant differences were found up to 6 months. Re-establishment of the blood-aqueous barrier was similar in eyes with the AcrySof, Hydroview, and MemoryLens IOLs; the course of postoperative inflammation was different in eyes with the silicone IOL. CONCLUSION: Comparison of postoperative flare values after implantation of 4 foldable IOLs showed no clinically relevant differences in the course of postoperative inflammation.

Male fetuses are particularly affected by maternal alloimmunization to D antigen.

BACKGROUND: It is hypothesized that male fetuses are more severely affected by fetomaternal alloimmunization to D antigen than female fetuses. STUDY DESIGN AND METHODS: One hundred four consecutive pregnancies with single D+ fetuses (51 males, 53 females) and maternal anti-D titers >16 were analyzed retrospectively. RESULT: Sixty fetuses (58%) received intrauterine transfusions. Male fetuses required more transfusions than females (5.0 vs. 2.0, p = 0.0001). At the initial transfusion, male fetuses had a lower gestational age (24.5 vs. 31.0 weeks, p = 0.0007), cord blood hemoglobin content (6.45 vs. 8.75 g/dL, p = 0.01), and hematocrit (19.8 vs. 26.8%, p = 0.004) than female fetuses. After adjustment for maternal gravidity, parity, and history of affected offspring, the odds ratio for development of hydrops by male fetuses was 13.1 (95% CI 2.69-63.6, p = 0.001). Perinatal mortality was higher in male (18%) fetuses than in female (6%) (adjusted odds ratio for males 3.38; 95% CI 0.59-19.46, p = 0.17). CONCLUSION: Male fetuses are particularly affected by maternal alloimmunization to D and require more intense antepartum surveillance than female fetuses.

Twenty years of the ethics committee at the medical faculty of the University of Vienna. An interim report.

The organisation and assessment procedures of the ethics committee of the University of Vienna medical faculty are described. Data concerning the work of the committee from 1993 through to 1997 are given in detail. Finally, the results of a survey among physicians on the acceptance of the committee's work are presented. In conclusion, the workload of an ethics committee in a large medical faculty can only be handled by efficient management of assessment procedures. However, it is difficult to achieve sufficient acceptance in a field governed by various interests.

Evaluation of cytomegalovirus retinitis management. Outcome of four years of cytomegalovirus therapy.

Cytomegalovirus (CMV) is the most common pathogen of opportunistic viral infections in patients with the acquired immunodeficiency syndrome. In this study, we assessed the therapeutic outcome of our treatment regimen of CMV retinitis by analysing retrospectively 33 consecutive patients. The clinical utility of CMV cultures from blood, urine and throat specimens obtained at the time of diagnosis was additionally evaluated. Treatment started with ganciclovir (GCV) therapy. In case of relapsing retinitis, re-induction therapy was initiated, and if unsuccessful, the patient was switched to foscarnet. Patients developing resistant retinitis despite foscarnet therapy were offered a GCV-foscarnet combination therapy. Under primary GCV therapy, the median first stable interval of the whole group was 202 days (mean 238 days). Twenty-five out of 33 CMV retinitis patients (76%) responded to initial GCV therapy. Eleven of these patients showed relapsing retinitis that could be stabilised in 3 patients solely with combination therapy. Eight patients did not respond to primary GCV therapy. Three of them improved with foscarnet, but 3 patients did not respond to either treatment. In 18 (56%) out of 32 patients, CMV cultures yielded positive results. Considering our series, we may conclude that in the majority of patients primary or secondary viral resistance can be overcome by dose increase, switching to the alternative drug or a combination therapy.

Postoperative inflammation after clear corneal and sclerocorneal incisions.

PURPOSE: To compare two standard small incision techniques for cataract surgery--clear corneal incision and sclerocorneal incision--with regard to postoperative disturbance of the blood-aqueous barrier (BAB). SETTING: Department of Ophthalmology, University of Vienna, Austria. METHODS: This prospective comparative study comprised 108 eyes with senile cataract. A clear corneal tunnel incision was made in 53 eyes and a sclerocorneal incision with tunnel preparation in 55. All other surgical procedures and postoperative medication were standardized. Postoperative BAB disruption was measured with a laser flare-cell meter (Kowa FC 1000) in an undilated pupil on 1, 3, 7, 14, 28, 60, and 90 days postoperatively. The values were compared using a two-sided t-test. RESULTS: In both groups, flare and cell values were highest on the first postoperative day. They gradually declined but without recovery of preoperative flare values on day 28. At no time was there a noticeable between-group difference in mean cell and flare values except for flare at day 14 (P = .04). CONCLUSION: Postoperative trauma, measured by the BAB disturbance, was equally low after clear corneal and sclerocorneal incisions.