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R J Navickis

Publications and source records attributed to R J Navickis.

15 recordsLinked to original sources
PubMed2004

Central venous access devices in haemophilia.

Central venous access devices (CVADs) can facilitate repeated and/or urgent administration of coagulation factors in haemophilic patients. We conducted a systematic review and meta-analysis of complication rates and risk factors for poor outcome. Forty-eight studies with a total of 2704 patients and 2973 CVADs were included. The primary indications for CVADs were immune tolerance therapy (34.9% of patients), difficult venous access (31.8%) and prophylaxis (29.1%). Fully implanted CVADs were employed in 77.4% of cases and external CVADs in 22.6%. A total of 1190 infections were reported, and the pooled incidence of infection was 0.66 per 1000 CVAD days [confidence interval (CI), 0.44-0.97 per 1000 CVAD days]. Among patients developing infection, the pooled time to first infection was 295 days (CI, 181-479 days). Presence of inhibitors was an independent risk factor for infection with an incidence rate ratio (IRR) of 1.67 (CI, 1.15-2.43). Infection was less likely in patients >6 years of age (IRR, 0.46; CI, 0.27-0.79) and recipients of fully implanted CVADs (IRR, 0.31; CI, 0.12-0.86). Available information on thrombosis was limited, with only 55 cases being reported. Eventually, 31.3% of CVADs were removed, and infection was the reason for removal in 69.9% of cases and thrombosis in 4.1%. The pooled time period CVADs remained indwelling prior to removal or the expiration of the study observation period was 578 days per CVAD (CI, 456-733 days per CVAD). CVADs can confer major benefits in patients with haemophilia requiring long-term venous access, and serious complications are rare.

Catheterization, Central Venous↗
PubMed2004

Increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII--a robust meta-analytic finding.

Meta-analyses of observational studies have become increasingly common to support evidence-based clinical decisions. We analyzed currently available clinical studies of full-length factor VIII (FL-FVIII) vs. B-domain deleted recombinant factor VIII (BDD-rFVIII) using a random effects model to investigate possible differences in clinical efficacy in patients treated during prophylaxis. Some studies reported breakthrough bleeding incidence as mean annual total bleeds, whereas others reported median bleeds. In accord with the consensus recommendations by the Meta-analysis of Observational Studies in Epidemiology (MOOSE) group, all available studies where included. For analysis, data were combined by converting median to mean annual total bleeds using a conversion factor of 2.6, based on clinical data previously compiled by the Universal Data Collection Program of the U.S. Centers for Disease Control and Prevention. To evaluate the sensitivity of our model upon the choice of conversion factor, we re-estimated incidence rate ratios for breakthrough bleeding over a wide range of conversion factors from 1.4-2.6. Even at the lowest extreme conversion factor of 1.4, bleeding incidence was statistically higher in patients treated with BDD-rFVIII compared with FL-FVIII. We also examined the impact of reported patient age on our multivariate model. Exposure to BDD-rFVIII remained an independent predictor of bleeding, regardless of patient age at start or mean age during prophylaxis. These analyses further support the robustness of our meta-analysis and its conclusions.

Age Factors↗
PubMed2004

Consensus recommendations for use of central venous access devices in haemophilia.

Venous access is essential for delivery of haemophilia factor concentrate. Wherever possible, peripheral veins remain the route of choice, and the use of central venous access devices (CVADs) should be limited to cases of clear need in patients with caregivers able to exercise diligence in CVAD care and should continue no longer than necessary. CVADs are of recognized value for repeated administration of coagulation factors in haemophilia, particularly for prophylaxis and immune tolerance therapy and in young children. Evidence to guide best practices has been fragmentary, and standardized methods for CVAD usage have yet to be established. We have developed management recommendations based upon available published evidence as well as extensive clinical experience. These recommendations address patient and CVAD selection; CVAD placement, care and removal; caregiver/patient guidance; and complications, including infection and thrombosis. In the absence of inhibitors, ports are recommended, primarily because of fewer associated infections than with external catheters. For patients with inhibitors, ports also appear to be associated with fewer infections. Infection is the most frequent complication, and recommendations to prevent and treat infections are supported by extensive clinical data and experience. Strict adherence to handwashing and aseptic technique are essential elements of catheter care. Evidence-based data regarding the detection and treatment of CVAD-related thrombotic complications are limited. Caregiver education is an integral part of CVAD use and the procedural practices of users should be regularly re-assessed. These recommendations provide a basis for sound current CVAD practice and are expected to undergo further refinements as new evidence is compiled and clinical experience is gained.

Catheterization, Central Venous↗
PubMed2004

Meta-analytic evidence of increased breakthrough bleeding during prophylaxis with B-domain deleted factor VIII.

A recent meta-analysis of 13 observational studies suggested reduced haemostatic efficacy during prophylaxis and shortened half-life of B-domain deleted factor VIII (BDD-rFVIII) as compared with full-length factor VIII (FL-FVIII). The meta-analysis included a multivariate model that took both dose and age into account. In addition, several assumptions and interpretations were required in order to conduct the meta-analysis. It is important to test the impact of such assumptions and interpretations through sensitivity analysis. In the published meta-analysis, results of several sensitivity analyses were described involving the effect of study design; heterogeneity of subjects in some studies; type of assay used for half-life determinations; and year of publication. In two subsequent brief reports, additional sensitivity analyses addressed choice of median-to-mean conversion factor over a wide range of scenarios and use of age at start of prophylaxis vs mean age during prophylaxis in the multivariate model. A recognized inherent difficulty in the meta-analysis of multiple published reports from similar studies is the possibility of some subject or data overlap. Therefore, the present communication details further sensitivity analyses encompassing assumptions regarding the possibility of subject duplication in a subgroup of subjects from one study and possible duplication of pharmacokinetic data from two smaller studies within the reports of two larger studies. All the sensitivity analyses support the main conclusions of the meta-analysis, namely, that BDD-rFVIII substantially increases the risk of breakthrough bleeding during prophylaxis, possibly at least partly because of shorter half-life than that of FL-FVIII.

Data Interpretation, Statistical↗
PubMed2003

Albumin administration--what is the evidence of clinical benefit? A systematic review of randomized controlled trials.

BACKGROUND AND OBJECTIVE: The advantages of albumin over less costly alternative fluids continue to be debated. Meta-analyses focusing on survival have been inconclusive, and other clinically relevant end-points have not been systematically addressed. We sought to determine whether albumin confers significant clinical benefit in acute illness compared with other fluid regimens. METHODS: Database searches (MEDLINE, EMBASE, Cochrane Library) and other methods were used to identify randomized controlled trials comparing albumin with crystalloid, artificial colloid, no albumin or lower-dose albumin. Major findings for all end-points were extracted and summarized. A quantitative meta-analysis was not attempted. RESULTS: Seventy-nine randomized trials with a total of 4755 patients were included. No significant treatment effects were detectable in 20/79 (25%) trials. In cardiac surgery, albumin administration resulted in lower fluid requirements, higher colloid oncotic pressure, reduced pulmonary oedema with respiratory impairment and greater haemodilution compared with crystalloid and hydroxyethylstarch increased postoperative bleeding. In non-cardiac surgery, fluid requirements, and pulmonary and intestinal oedema were decreased by albumin compared with crystalloid. In hypoalbuminaemia, higher doses of albumin reduced morbidity. In ascites, albumin reduced haemodynamic derangements, morbidity and length of stay and improved survival after spontaneous bacterial peritonitis. In sepsis, albumin decreased pulmonary oedema and respiratory dysfunction compared with crystalloid, while hydroxyethylstarch induced abnormalities of haemostasis. Complications were lowered by albumin compared with crystalloid in burn patients. Albumin-containing therapeutic regimens improved outcomes after brain injury. CONCLUSIONS: Albumin can bestow benefit in diverse clinical settings. Further trials are warranted to delineate optimal fluid regimens, in particular indications.

Acute Disease↗
PubMed2003

Comparative effectiveness of full-length and B-domain deleted factor VIII for prophylaxis--a meta-analysis.

Recently reported data suggest the possibility of differences in clinical efficacy between full-length factor VIII (FL-FVIII) and B-domain deleted recombinant factor VIII (BDD-rFVIII). To address this question, we conducted a meta-analysis of studies reporting the incidence of bleeding under prophylaxis, as well as studies of FL-FVIII and BDD-rFVIII half-life. The pooled cumulative weekly prophylactic dose of BDD-rFVIII (81.3 +/- 13.8 IU kg(-1) week(-1)) was greater by 36% (P = 0.11) than that of FL-FVIII (60.0 +/- 5.9 IU kg(-1) week(-1)). The pooled incidence of bleeding in BDD-rFVIII recipients [16.8 bleeds per patient year; confidence interval (CI), 9.5-24.2 bleeds per patient year] was more than 2.5-fold larger (P < 0.0005) than that in patients receiving FL-FVIII (6.6 bleeds per patient year; CI, 4.7-8.5 bleeds per patient year). In a multivariate analysis, the incidence rate ratio was 2.10 (CI, 1.98-2.24), indicating that breakthrough bleeding under prophylaxis was more than twice as likely with BDD-rFVIII than FL-FVIII at equivalent doses and ages. The pooled half-life for plasma-derived FL-FVIII (13.7 h; CI, 12.8-14.6 h) was closely similar to that for recombinant FL-FVIII (14.3 h; CI, 13.3-15.4 h). By contrast, the pooled half-life for BDD-rFVIII (11.3 h; CI, 9.9-12.7 h) was shorter by approximately 3 h compared with FL-FVIII. Although the results of the meta-analysis need to be interpreted with caution, the pooled data suggest that breakthrough bleeding under prophylaxis may occur more frequently in patients receiving BDD-rFVIII than FL-FVIII and may at least partly reflect a more abbreviated half-life of BDD-rFVIII. Several biochemical differences between BDD-rFVIII and FL-FVIII may underlie the observed disparities in bleeding incidence and half-life. This meta-analysis should be confirmed by further studies.

Adolescent↗
PubMed2003

Safety of human albumin--serious adverse events reported worldwide in 1998-2000.

BACKGROUND: Previous pharmacovigilance studies have indicated a low rate of adverse events in patients receiving human albumin. However, the incidence of adverse events is likely to have been underestimated because of under-reporting. A more accurate estimate may be possible during a period such as 1998-2000, when awareness regarding albumin safety was heightened by publication of a meta-analysis. METHODS: All serious adverse event reports received, and total doses of albumin distributed worldwide from the beginning of 1998 to the end of 2000 by 10 major suppliers of therapeutic human albumin were compiled. RESULTS: Distributed albumin doses totalled 1.62 x 10(7). The total numbers of non-fatal and fatal serious adverse events reported were 198 and 13, respectively. The incidence of all reported serious non-fatal and fatal adverse events was 5.28 per 10(6) doses (CI 1.60-17.4 per 10(6) doses). For non-fatal serious adverse events only, the observed incidence was 4.65 per 10(6) doses (CI 1.34-16.2 per 10(6) doses). No patient death was classified as probably related to albumin administration. The observed incidence of fatal serious adverse events possibly related to albumin was 0.185 per 10(6) doses (CI 0.0597-0.574 per 10(6) doses). The observed incidence of all non-fatal and fatal serious adverse events was significantly higher during the 1998-2000 period as compared with 1990-1997 (incidence rate ratio 4.98; CI 3.94-6.29), probably chiefly as a result of reduced under-reporting. CONCLUSIONS: Although the observed incidence of adverse events is likely to be an underestimate, nevertheless both non-fatal and fatal serious adverse events in albumin recipients appear to be rare. These results add further support to the excellent safety record of human albumin.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Patient survival after human albumin administration. A meta-analysis of randomized, controlled trials.

PURPOSE: To test the hypothesis that albumin administration is not associated with excess mortality. DATA SOURCES: Computer searches of the MEDLINE and EMBASE databases, the Cochrane Library, and Internet documents; hand searching of medical journals; inquiries to investigators and medical directors; and review of reference lists. STUDY SELECTION: Randomized, controlled trials comparing albumin therapy with crystalloid therapy, no albumin, or lower doses of albumin. DATA EXTRACTION: Two investigators independently extracted data. The primary end point was relative risk for death. Criteria used to assess methodologic quality were blinding, method of allocation concealment, presence of mortality as a study end point, and crossover. Small-trial bias was also investigated. DATA SYNTHESIS: Fifty-five trials involving surgery or trauma, burns, hypoalbuminemia, high-risk neonates, ascites, and other indications were included. Albumin administration did not significantly affect mortality in any category of indications. For all trials, the relative risk for death was 1.11 (95% CI, 0.95 to 1.28). Relative risk was lower among trials with blinding (0.73 [CI, 0.48 to 1.12]; n = 7), mortality as an end point (1.00 [CI, 0.84 to 1.18]; n = 17), no crossover (1.04 [CI, 0.89 to 1.22]; n = 35), and 100 or more patients (0.94 [CI, 0.77 to 1.14]; n = 10). In trials with two or more such attributes, relative risk was further reduced. CONCLUSIONS: Overall, no effect of albumin on mortality was detected; any such effect may therefore be small. This finding supports the safety of albumin. The influence of methodologic quality on relative risk for death suggests the need for further well-designed clinical trials.

Albumins↗
PubMed2001

Albumin versus hydroxyethyl starch in cardiopulmonary bypass surgery: a meta-analysis of postoperative bleeding.

BACKGROUND: This meta-analysis tested the hypothesis that cumulative blood loss during the first 24 hours after cardiopulmonary bypass is lower in patients exposed to albumin than hydroxyethyl starch (HES). METHODS: Randomized controlled trials comparing albumin and HES in cardiopulmonary bypass patients were identified by bibliographic database searches and other methods. RESULTS: Sixteen trials involving 653 randomized patients were included. In 88% of randomized comparisons, postoperative bleeding was lower in the albumin group, and the standardized mean difference in bleeding favoring albumin across all trials (-0.24; 95% confidence interval, -0.40 to -0.08) was statistically significant. Bleeding differences between albumin and either high or medium molecular weight HES were similar. In trials of adults, the pooled mean blood loss in the albumin group was 693+/-350 mL compared with 789+/-487 mL in the HES group. The estimated proportion of adult albumin group patients with blood loss of more than 1,000 mL was 19% compared with 33% of adult HES group patients. Conclusions. Postoperative blood loss is significantly lower in cardiopulmonary bypass patients exposed to albumin than HES.

Aged↗
PubMed1999

Salvage brachytherapy for localized prostate cancer after radiotherapy failure.

OBJECTIVES: To evaluate the effectiveness and morbidity of salvage brachytherapy for locally recurrent or persistent prostate cancer after radiotherapy failure. METHODS: In this retrospective study, 49 patients of median age 73.3 years (range 52.9 to 86.9) with biopsy-proven localized prostate cancer underwent interactive transperineal fluoroscopic-guided and biplane ultrasound-guided brachytherapy with either iodine 125 or palladium 103 after prior radiotherapy failure. Post-treatment follow-up was conducted for a median of 64.1 months (range 26.6 to 96.8) and included clinical assessment of disease status, assays of serum prostate-specific antigen (PSA) levels, and documentation of treatment-related symptoms and complications. Determination of biochemical treatment failure was based on two successive rising PSA values above the post-treatment PSA nadir value. RESULTS: The actuarial rate of local prostate cancer control was 98% (95% confidence interval [CI] 94% to 99%). Actuarial disease-specific survival at 3 and 5 years was 89% (95% CI 73% to 96%) and 79% (95% CI 58% to 91%), respectively. At 3 and 5 years, actuarial biochemical disease-free survival was 48% (95% CI 32% to 63%) and 34% (95% CI 17% to 51%), respectively. Post-treatment PSA nadir was found to be a significant predictor of biochemical disease-free survival. Actuarial biochemical disease-free survival of patients who achieved a PSA nadir less than 0.5 ng/mL was 77% (95% CI 53% to 90%) and 56% (95% CI 25% to 78%) at 3 and 5 years, respectively. Of 49 patients, 23 (47%) achieved a post-treatment PSA nadir less than 0.5 ng/mL. The incidence of serious complications after salvage brachytherapy, such as incontinence and rectal complications, was lower than that reported after other types of salvage procedures. CONCLUSIONS: Interactive transperineal fluoroscopic-guided and biplane ultrasound-guided brachytherapy is a novel, potentially curative salvage modality for patients in whom prior radiotherapy failed. In a population of patients with poor prognosis, this modality was associated with a high rate of local prostate cancer control and a 34% actuarial rate of biochemical disease-free survival at 5 years. The incidence of major complications after salvage brachytherapy appears to be lower than that after other potentially curative salvage procedures, such as radical prostatectomy and cryoablation. Salvage brachytherapy warrants further investigation.

Actuarial Analysis↗
PubMed1998

Actuarial disease-free survival after prostate cancer brachytherapy using interactive techniques with biplane ultrasound and fluoroscopic guidance.

PURPOSE: To evaluate the effectiveness and safety of interactive transperineal brachytherapy under biplane ultrasound and fluoroscopic guidance in patients with localized prostate cancer. METHODS AND MATERIALS: Brachytherapy using 125I or 103Pd radioactive seeds either alone or in combination with adjunctive external beam radiotherapy (XRT) was administered to 490 patients at a single institution. Post-treatment follow-up included clinical assessment of disease status, assays of serum prostate-specific antigen (PSA) levels and documentation of treatment-related symptoms and complications. RESULTS: Actuarial disease-free survival at 5 yr was 79% (95% CI, 71-85%), and the 5-yr actuarial rate of local control was 98% (95% CI, 94-99%). Post-treatment PSA nadir and pretreatment PSA level were found to be significant predictors of disease-free survival. In patients with a PSA nadir < 0.5 ng/ml, 5-yr disease-free survival was 93% (95% CI, 84-97%), compared with 25% (95% CI, 5-53%) in patients whose PSA nadir was 0.5-1.0 ng/ml and 15% (95% CI, 3-38) in patients with a PSA nadir > 1.0 ng/ml. Brachytherapy was well tolerated with few post-treatment complications. CONCLUSION: A broad range of patients with localized prostate cancer can benefit from transperineal brachytherapy with minimal morbidity. A post-treatment PSA nadir below 0.5 ng/ml provides a useful prognostic indicator of favorable long-term outcome.

Aged↗
PubMed1982

Modulation of prolactin receptors in cultured rat granulosa cells by FSH, LH and GnRH.

The hormonal modulation of prolactin (PRL)-binding capacity of rat granulosa cells was studied. Granulosa cells obtained from immature, hypophysectomized, estrogen-treated rats were cultured for 2 days in a serum-free medium in the presence of various hormones. FSH treatment in vitro stimulated granulosa cell PRL-binding capacity by approximately 4-6-fold in a dose-dependent manner. Concomitant treatment with 10-8 M GnRH inhibited the FSH-induced increase in PRL-binding capacity by 64%. In contrast, the inhibitory effect of GnRH was blocked by concomitant treatment with 10-6 M of a GNRH antagonists, [D-pGlu1, D-Phe2, D-Trp3,6]GnRH. PRL-binding capacity was also increased (approximately 2-fold) by in vitro treatment with cholera toxin (10 microgram/ml). In granulosa cells pre-treated with FSH in vitro for 2 days, hCG treatment for 2 additional days stimulated PRL-binding capacity in a dose-dependent manner (approximately 2-fold). Likewise, treatment with LH (100 ng/ml) also stimulated PRL-binding capacity by approximately 2-fold. These in vitro studies demonstrated that gonadotropins (FSH, LH and hCG) directly enhanced PRL binding by granulosa cells, whereas GnRH inhibited FSH action.

Animals↗
PubMed1981

Increase in testis luteinizing hormone receptor by estrogen in mice susceptible to Leydig cell tumors.

In an investigation comparing two strains of mice (BALB/c, susceptible to estrogen-induced Leydig cell tumors and C3H, resistant to such tumors), we found that the Leydig cell-luteinizing hormone (LH) receptors increase in BALB/c mice and decrease in C3H mice during estrogen treatment. In the BALB/c strain, LH receptor content in the tested of mice treated 1, 2, 4, 6, or 8 weeks with diethylstilbestrol (DES) was 2.4- to 5.4-fold greater than that in the testes of untreated littermates. By 24 weeks of treatment, the receptor number had increased 10-fold. Likewise, two weeks of estradiol benzoate treatment in BALB/c mice resulted in a dose-dependent increase in LH receptor content. In contrast, in C3H mice, DES treatment resulted in a transient initial increase (60%), followed by a time-dependent decrease in testicular LH receptor number: 38 and 17% that of normal by six and eight weeks of treatment, respectively. In both strains of mice, DES-induced changes in 125I-labeled human chorionic gonadotropin binding reflected changes in LH receptor number rather than in receptor affinity (approximately 3 x 10(-11) M). The testis weights of BALB/c mice remained normal during DES treatment, whereas those of the C3H decreased with time. Sprague-Dawley rats, resistant to estrogen-induced Leydig cell tumors, like C3H mice, also underwent testicular atrophy and lost LH receptors during DES treatment. The present study demonstrates that estrogen treatment indices diametrically oppossed change in testicular LH receptor number in the two strains of mice with different susceptibilities to Leydig cell tumorigenesis.

Animals↗