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L Duchateau

Publications and source records attributed to L Duchateau.

66 records · Page 4Linked to original sources

The role of meta-analyses in assessing cancer treatments.

The results of individual phase III cancer clinical trials are often inconclusive due to the overly optimistic size of treatment differences that are sought. Increased power and precision can generally be obtained if the data from several different trials studying the same or similar questions are analysed together. Individual patient data meta-analyses, which combine together the quantitative results from all properly randomised studies, provide an overall estimate of the size of treatment differences. Individual patient data meta-analyses have played an especially important role in breast and gastrointestinal tract cancers where many important questions have been addressed. Although meta-analyses have been subject to considerable criticism, individual patient data meta-analyses provide the best overall evidence of treatment effect in the absence of large-scale trials and have been instrumental in providing objective data that can be used in the design of new studies.

Decision Making↗

Estimating number of events from the Kaplan-Meier curve for incorporation in a literature-based meta-analysis: what you don't see you can't get!

In literature-based meta-analyses of time-to-event data, the number of events in the treated and control groups together with the total number of patients randomized to the two treatment arms are often used as summary statistics. If interest is in mortality at a specified moment in time, the number of events can, in most cases, only be obtained from the Kaplan-Meier curve. The estimated number of events, however, is typically larger than the true number of events. The effect of this overestimation on the Mantel-Haenszel test and the odds ratio is studied in this paper. From these results, it can be concluded that the number of events should not be estimated from the Kaplan-Meier curves for meta-analytic purposes unless virtually no patients are lost to follow-up or censored and there are still many patients at risk in the two groups at the time at which the number of events is to be determined.

Follow-Up Studies↗

Promising results with exemestane in the first-line treatment of metastatic breast cancer: a randomized phase II EORTC trial with a tamoxifen control.

Because tamoxifen (TAM), a nonsteroidal antiestrogen, is routinely used in the adjuvant setting, other hormone therapies are needed as alternatives for first-line treatment of metastatic breast cancer (MBC). Currently, exemestane (EXE) and other antiaromatase agents are indicated for use in patients who experience failure of TAM. In this multicenter, randomized, open-label, TAM-controlled (20 mg/day), phase II trial, we examined the activity and tolerability of EXE 25 mg/day for the first-line treatment of MBC in postmenopausal women. Exemestane was well tolerated and demonstrated substantial first-line antitumor activity based on intent-to-treat analysis of peer-reviewed responses. In the EXE arm, values for complete, partial, and objective response, clinical benefit, and time to tumor progression (TTP) exceeded those reported for TAM although no statistical comparison was made. Based on these encouraging results, a phase III trial will compare EXE and TAM.

Administration, Oral↗

Power evaluation of small drug and vaccine experiments with binary outcomes.

Power analysis based on the Fisher exact test is used to evaluate the usefulness of alternative designs for small drug and vaccine experiments with a binary, success or failure, outcome. The emphasis is on the comparison between designs with equal and unequal allocations of animals to treated and control groups having the same total sample size, and between designs with equal and unequal allocations but with one or two fewer animals in the control than the treated group. Designs with unequal allocation can sometimes be more powerful at a given level of statistical significance alpha than designs with equal allocation. Graphs and a table are presented to aid the choice of suitable designs for (1-beta) = 0.80 and alpha = 0.05.

Animal Welfare↗

Immunisation with live attenuated Salmonella dublin expressing a sporozoite protein confers partial protection against Theileria parva.

Cattle immunised with a recombinant form of p67, the major surface antigen of Theileria parva sporozoites, have been shown to be protected against parasite challenge. In an attempt to simplify the immunisation procedure live attenuated Salmonella strains expressing p67 have been constructed and used to induce anti-p67 immune responses in cattle. All animals immunised with these strains developed strong antibody responses to p67. Specific T cell responses could be detected in the majority of immunised cattle. Challenge with T. parva sporozoites revealed a significant level of protection in immunised calves compared to naive control animals or animals inoculated with non-recombinant attenuated Salmonella.

Animals↗

Delivery of the Theileria parva p67 antigen to cattle using recombinant vaccinia virus: IL-2 enhances protection.

To evaluate vaccinia virus as a delivery system for recombinant antigen in cattle, calves were immunized with a recombinant vaccinia virus (rVV) expressing the sporozoite surface antigen (p67) of Theileria parva (V-67) combined with those expressing bovine IL-4 (V-IL4) or IL-2 (V-IL2). The anti-p67 antibody levels detected in calves inoculated with the combination of V-67 and V-IL4 were higher than those produced by animals injected with V-67 alone or V-67 and V-IL2. On challenge with cryopreserved sporozoites, 5 of 7 animals receiving V-67 combined with V-IL2 were protected, while those receiving V-67 in conjunction with V-IL4 behaved like unimmunized control calves. Vaccination with a recombinant virus expressing a chimaeric p67(p583)/IL2 product gave rise to a lower level of protection, whereas V-IL2 provided no immunity. The results of this study demonstrate the potential of rVV as a delivery system for use in vaccination of cattle against Theileria parva infection.

Adjuvants, Immunologic↗

Pooling sera to reduce the cost of HIV surveillance: a feasibility study in a rural Kenyan district.

Seroprevalence studies are crucial in HIV control programs but too expensive at district level. We evaluated the applicability of pooling sera and how it can reduce cost and affect accuracy at district level. 740 samples collected from antenatal clinic attendants for a sentinel survey in a rural Kenyan district were screened individually and in pools of 10. The seroprevalence when measured individually was 7.30%, while the calculated seroprevalence from pooled testing was 7.49%. Pooling was practicable and reduced costs by 62% for a marginal loss of accuracy. It is a useful tool in increasing the affordability of surveillance at district level. A pool size of 8 would have resulted in optimal cost reduction at minimal loss of accuracy.

Blood Specimen Collection↗

Reducing a spatial database to its effective dimensionality for logistic-regression analysis of incidence of livestock disease.

Large databases with multiple variables, selected because they are available and might provide an insight into establishing causal relationships, are often difficult to analyse and interpret because of multicollinearity. The objective of this study was to reduce the dimensionality of a multivariable spatial database of Zimbabwe, containing many environmental variables that were collected to predict the distribution of outbreaks of theileriosis (the tick-borne infection of cattle caused by Theileria parva and transmitted by the brown ear tick). Principal-component analysis and varimax rotation of the principal components were first used to select a reduced number of variables. The logistic-regression model was evaluated by appropriate goodness-of-fit tests.

Animals↗

Implant stability related to insertion torque force and bone density: An in vitro study.

Seventy-five implants were installed in 12 fresh ethanol-treated bovine ribs by use of a torque gauge manometer to measure the force needed to screw the implants fully into the bone. Digital radiographs were taken and a density histogram of the bone at the implant/bone interface was obtained. The damping characteristics of the implant/bone interface were assessed by tapping the abutment with the Periotest (PT) device. Abutments of several lengths screwed at 20 N/cm were used to conduct PT measurements and the PT values (PTVs) were related to the insertion torque force, the bone density, and implant and abutment length. The results indicated that high correlations exist between PTVs and insertion torque force (R value -0.74579), and PTVs and bone density (R value -0.83031). There was also a significant difference (p 0.001) among the PTVs of the different abutment lengths used. Implant length did not demonstrate influence on PTVs (p 0.3847).

Analysis of Variance↗

The inflammatory response in the mouse stomach to Helicobacter bizzozeronii, Helicobacter salomonis and two Helicobacter felis Strains.

The inflammatory response in the mouse stomach was evaluated as a means of distinguishing different non-pylori Helicobacter (H.) strains in terms of virulence. Mice of four strains (BALB/c, SJL, C57BL/6 and CFW) were infected intragastrically with four bacterial strains (H. felis ATCC 49179 and CCUG 37471, H. bizzozeronii and H. salomonis). The animals were killed for gastric examination at 3, 9 or 16 weeks post-inoculation. H. salomonis could not be detected by the polymerase chain reaction, but the other three organisms were detected in all stomach samples at all timepoints. SJL mice consistently showed particularly severe gastric inflammation regardless of bacterial strain. Lymphocytes and occasionally neutrophils were seen in submucosa and lamina propria mucosae. BALB/c mice showed the least severe inflammatory changes. H. bizzozeronii differed from the two H. felis strains in producing less striking pathological changes in mice. Of the two H. felis strains, ATCC 49179 produced the more severe inflammatory changes in SJL mice.

Animals↗

Investigation of physiologic leukopenia in Belgian Tervuren dogs.

BACKGROUND: Physiologic leukopenia in Tervuren dogs was reported in North America with a higher frequency in aged Tervurens. If not recognized, physiologic leukopenia can provoke unnecessary clinical investigations. HYPOTHESIS: The primary objective was to compare Tervurens and control dogs in Belgium with respect to the numbers of dogs with physiologic leukopenia. The secondary objectives were to compare Tervurens with control dogs and age classes within Tervurens and controls for parameters related to physiologic leukopenia. ANIMALS: Tervurens (n = 94) and control dogs (n = 48, maximum of 5 dogs per breed and 5 mixed breed dogs) were entered into the study. Dogs were 1-11 years old and healthy on routine physical examination. Dogs had no history of disease or drug administration in the previous 2 months. METHODS: Hematologic analyses were performed by an automated device within 30 hours of sampling. Blood smears were evaluated for cellular morphologic anomalies. RESULTS: Only 1 of the 94 Tervuren dogs had physiologic leukopenia (1.06%; 95% confidence interval, 0.05-5.22). Furthermore, the white blood cell (WBC) count in Tervuren dogs (median, 10.00 x 109/L; range, 5.90-20.80) was not significantly different (P = .55) from that of control dogs (median, 9.75 x 109/L; range, 5.20-20.90). The WBC count decreased significantly (P < .001) with age in Tervuren dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: Physiologic leukopenia is uncommon in the Belgian Tervuren dog. Differences with earlier data published in North America might be due to genetic or environmental differences.

Age Factors↗

Effect of storage of reconstituted recombinant human thyroid-stimulating hormone (rhTSH) on thyroid-stimulating hormone (TSH) response testing in euthyroid dogs.

Bovine thyrotropin (bTSH) stimulation testing has long been considered the gold standard for diagnosis of canine hypothyroidism. Unfortunately, bTSH is no longer commercially available. Recently, the use of recombinant human thyrotropin (rhTSH) to perform thyroid-stimulating hormone (TSH) stimulation testing in dogs was described. The cost of an rhTSH vial (1.1 mg) limits the practical use of this product. The study reported here was performed to determine the effects of storing rhTSH on the post-TSH increase of serum total (TT4) and free (FT4) thyroxine concentrations during TSH stimulation testing in 12 euthyroid Beagles in a crossover trial. Three TSH tests with recombinant human thyrotropin (rhTSH; 91.5 microg IV) were performed on each dog during 3 different periods: 1 with freshly reconstituted rhTSH (fresh); 1 with rhTSH, reconstituted and stored at 4 degrees C for 4 weeks (refrigerated); and 1 with rhTSH, reconstituted and frozen at -20 degrees C for 8 weeks (frozen). Blood samples for determination of TT4 and FT4 concentrations were collected before and 4 and 6 hours after rhTSH administration. There was no significant difference in TT4 or FT4 concentration after stimulation with fresh, refrigerated, and frozen rhTSH. Furthermore, there was no significant difference between TT4 or FT4 serum concentration observed 4 and 6 hours after rhTSH administration. In conclusion, reconstituted rhTSH can be stored at 4 degrees C for 4 weeks and at -20 degrees C for 8 weeks without loss of biological activity, allowing clinicians to perform more TSH response tests per vial.

Animals↗