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J Bogaerts

Publications and source records attributed to J Bogaerts.

At least 19 recordsLinked to original sources

Clinical trials design and treatment tailoring: general principles applied to breast cancer research.

Nowadays tailored therapy tends to replace standard cancer treatment approaches. Tailoring treatment is possible thanks to clinical trials results that identified subgroups of patients benefiting most from some treatments. Treatment can be tailored on the basis of specific clinical characteristics of the population or on the basis of predictive or prognostic markers. Finally treatment can be tailored for specific molecular targets. This evolution in cancer treatment has triggered the development of innovative trial designs to validate these new hypotheses. The real challenge of the next coming years resides in recruiting large number of patients from specific subgroups to validate tailored therapies.

Biomarkers, Tumor↗

Phase III randomised trial comparing paclitaxel/carboplatin with paclitaxel/cisplatin in patients with advanced non-small-cell lung cancer: a cooperative multinational trial.

BACKGROUND: The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer (NSCLC). This phase III study of chemotherapy-naïve advanced NSCLC patients was designed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination. Paclitaxel was given at a dose of 200 mg/m(2) (3-h intravenous infusion) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2), all repeated every 3 weeks. Survival, toxicity and quality of life were also compared. PATIENTS AND METHODS: Patients were randomised to receive one of the two combinations, stratified according to centre, performance status, disease stage and histology. The primary analyses of response rate and survival were carried out on response-evaluable patients. Survival was also analysed for all randomised patients. Toxicity analyses were carried out on all treated patients. RESULTS: A total of 618 patients were randomised. The two treatment arms were well balanced with regard to gender (83% male), age (median 58 years), performance status (83% ECOG 0-1), stage (68% IV, 32% IIIB) and histology (38% squamous cell carcinoma). In the paclitaxel/carboplatin arm, 306 patients received a total of 1311 courses (median four courses, range 1-10 courses) while in the paclitaxel/cisplatin arm, 302 patients received a total of 1321 courses (median four courses, range 1-10 courses). In only 76% of courses, carboplatin was administered as planned at an AUC of 6, while in 96% of courses, cisplatin was given at the planned dose of 80 mg/m(2). The response rate was 25% (70 of 279) in the paclitaxel/carboplatin arm and 28% (80 of 284) in the paclitaxel/cisplatin arm (P = 0.45). Responses were reviewed by an independent radiological committee. For all randomised patients, median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [hazard ratio 1.20, 90% confidence interval (CI) 1.03-1.40]; the 1-year survival rates were 33% and 38%, respectively. On the same dataset, a survival update after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm (hazard ratio 1.22, 90% CI 1.06-1.40; P = 0.019); the 2-year survival rates were 9% and 15%, respectively. Excluding neutropenia and thrombocytopenia, which were more frequent in the paclitaxel/carboplatin arm, and nausea/vomiting and nephrotoxicity, which were more frequent in the paclitaxel/cisplatin arm, the rate of severe toxicities was generally low and comparable between the two arms. Overall quality of life (EORTC QLQ-C30 and LC-13) was also similar between the two arms. CONCLUSIONS: This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC. Although paclitaxel/carboplatin yielded a similar response rate, the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option.

Adult↗

Local production of anti-vibrio cholerae mucosal antibody in reproductive tract tissues after cholera.

To investigate whether intestinal presentation of an antigen by Vibrio cholerae, a noninvasive organism, could induce an anatomically distant mucosal immune response in reproductive tract tissues, the endocervical immune responses of women in Bangladesh were evaluated after cholera. Endocervical secretions were analyzed for secretory IgA (sIgA) antibody against the B subunit of cholera toxin (CtxB) in 9 women with cholera and 8 women with diarrhea caused by neither V. cholerae nor heat labile enterotoxin-producing Escherichia coli. Women infected with V. cholerae developed significant sIgA anti-CtxB responses in endocervical samples (P< or =.02). Antibody subtype analysis of endocervical IgA was consistent with local mucosal production (P< or =.001). Women with cholera did not develop sIgA anti-CtxB responses in serum. The ability to generate specific mucosal immune responses in reproductive tract tissues after intestinal presentation of antigen could facilitate development of vaccines effective against reproductive tract pathogens.

Adolescent↗

Sexually transmitted infections among married women in Dhaka, Bangladesh: unexpected high prevalence of herpes simplex type 2 infection.

OBJECTIVES: To document the prevalence of reproductive tract infections (RTI) and sexually transmitted infections (STI) among women attending a basic healthcare clinic in Dhaka, Bangladesh, to identify risk factors associated with the diseases and to estimate the incidence of syphilis, hepatitis C (HCV), hepatitis B (HBV), and herpes simplex type 2 (HSV-2) infection. METHODS: A cross sectional sample of 2335 consecutive women was examined during 1996-8. Women were interviewed about risk factors for RTI/STI and tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis, Treponema pallidum, HIV, HCV, HBV, HSV-1 and HSV-2 infection as well as vaginal candidosis and bacterial vaginosis. Women with antibodies to T pallidum were retested at regular intervals. One year after ending the study seroconversion for syphilis, HBV, HCV, and HSV-2 infection was detected among women initially negative for the respective diseases. RESULTS: The overall prevalence rate of N gonorrhoeae, C trachomatis, T vaginalis, and T pallidum infection was 0.5%, 1.9%, 2.0%, and 2.9% respectively. Overall, 35% of the women had antibodies to hepatitis B core antigen, 0.9% had HCV, and 12% HSV-2 infection. Risk factors for gonorrhoea/C trachomatis infection were a husband not living at home or suspected of being unfaithful. HSV-2 infection was associated with the same risk factors and with a polygamous marriage. The prevalence of HSV-2 infection among women "at risk" was 23%. HIV infection was not diagnosed. Repeated serological examination indicated that only 32% of women with serological evidence of syphilis had active disease. The seroincidences of HBV, HCV, and HSV-2 were 0.03, 0.007, and 0.009 per person year. Seroconversion for syphilis was not observed.

Adolescent↗

Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer.

PURPOSE: New effective chemotherapy is needed to improve the outcome of patients with advanced non-small-cell lung cancer (NSCLC). Paclitaxel administered as a single agent or in combination with cisplatin has been shown to be a potentially new useful agent for the treatment of NSCLC. PATIENTS AND METHODS: Between January 1995 and April 1996, 414 patients with stage IIIB or IV NSCLC were randomized to received either a control arm of high-dose cisplatin (100 mg/m(2)) or a combination of paclitaxel (175 mg/m(2), 3-hour infusion) and cisplatin (80 mg/m(2)) every 21 days. RESULTS: Compared with the cisplatin-only arm, there was a 9% improvement (95% confidence interval, 0% to 19%) in overall response rate for the paclitaxel/cisplatin arm (17% v 26%, respectively; P=.028). Median time to progression was 2.7 and 4.1 months in the control and paclitaxel/cisplatin arm, respectively (P=.026). The study, however, failed to show a significant improvement in median survival for the paclitaxel/cisplatin arm (8.6 months in the control arm v 8.1 months in the paclitaxel/cisplatin arm, P=.862). There was more hematotoxicity, peripheral neuropathy, and arthralgia/myalgia on the paclitaxel/cisplatin arm, whereas the high-dose cisplatin arm produced more ototoxicity, nausea, vomiting, and nephrotoxicity. Quality of life (QOL) was similar overall between the two arms. CONCLUSION: This large randomized phase III trial failed to show a significant improvement in survival for the paclitaxel/cisplatin combination compared with high-dose cisplatin in patients with advanced NSCLC. However, the paclitaxel/cisplatin combination did produce a better clinical response, resulting in an increased time to progression while providing a similar QOL.

Adult↗

AIDS-associated cryptococcal meningitis in Rwanda (1983-1992): epidemiologic and diagnostic features.

OBJECTIVES: to document the trend of AIDS-associated Cryptococcus neoformans meningitis (CM) in Kigali, Rwanda, during 1983-1992, and to highlight some diagnostic and epidemiological features of the disease. METHODS: during the study period, 3476 cerebrospinal fluid (CSF) specimens from 2824 adults (1578 men, 1246 women) were analysed in the Laboratory of Microbiology at the Centre Hospitalier de Kigali, Rwanda, Central Africa, using direct examination, culture and detection of the cryptococcal antigen (CrAg) in the CSF. RESULTS: CM was diagnosed among 549 (19%) patients (347 men, 202 women) and was by far the leading cause of meningitis before Neisseria meningitidis (n=115), Streptococcus pneumoniae (n=68), Mycobacterium tuberculosis (n=26). E. coli, Klebsiella pneumoniae, non-typhoid Salmonella (n=l5) and streptococci (n=4). The number of CM increased from one case in 1983 to 130 new cases in 1992. All 293 tested CM patients had HIV-1 antibodies. The male/female ratio declined from 3.31 during 1983-1987 to 1.58 during 1988-1992. CM showed a seasonal fluctuation, the highest number of infections being observed during the long rainy season. The sensitivity and specificity of the latex test for diagnosing CM was 98% and 99%, respectively. Cryptococcus neoformans var. gattii was cultured from eight (1.6%) of the 499 culture positive patients. CONCLUSION: CM is an important opportunistic infection among AIDS patients in Central Africa. It remains a problematic diagnosis in areas with limited diagnostic facilities.

AIDS-Related Opportunistic Infections↗

Auxotypes, serovars, and trends of antimicrobial resistance of Neisseria gonorrhoeae in Kigali, Rwanda (1985-93).

OBJECTIVE: To investigate the in vitro antimicrobial susceptibility and the auxotype/serovar distribution of Neisseria gonorrhoeae in Kigali, Rwanda, during 1985-93. METHODS: As part of a monitoring programme the in vitro susceptibility of 1604 isolates of N gonorrhoeae was determined by agar dilution. Auxo- and serotyping was performed on 1350 and 1313 isolates respectively. RESULTS: The prevalence of penicillinase producing N gonorrhoeae (PPNG) remained stable at a rate of 39% during 1985-91 and increased to 61% in 1992-3. Chromosomal resistance to penicillin was common among non-PPNG and resistance to thiamphenicol and tetracycline was common among both PPNG and non-PPNG. High level, plasmid mediated resistance to tetracycline (TRNG) was observed for the first time at the end of 1989 and increased from 2% of the isolates in 1990 to 50% by 1993. A trend for increasing resistance to norfloxacin and ofloxacin was observed during 1985-90 but disappeared in 1991-93. Five isolates with high level resistance to norfloxacin (MIC 2 mg/l) were observed in 1990. Resistance to trimethoprim-sulphamethoxazole (TMP-SMZ) emerged at the end of 1990 and was observed among 10% of the isolates during 1991-3. All strains remained susceptible to ofloxacin, ciprofloxacin, spectinomycin, and ceftriaxone. Overall, 75% of the isolates were prototrophic or required proline for their growth and 62% belonged to serovars IA-6 and IB-1. The prevalence of serovar IB-4 increased strongly during the last 3 years of the study. CONCLUSION: Resistance to penicillin, thiamphenicol, and tetracycline was common in N gonorrhoeae during 1985-1993. The rapid spread of TRNG after 1989 and the steep increase of PPNG during 1992-3 were the most striking facts of the study period. The auxotype and serovar distribution was comparable with findings from other African countries.

Drug Resistance, Multiple↗

Genital ulcers in a primary health clinic in Rwanda: impact of HIV infection on diagnosis and ulcer healing (1986-1992).

During 1986-88 and 1990-92, 1025 (97%) out of 1057 genital ulcer patients in Kigali, Rwanda, were tested for HIV antibodies and for infection with Treponema pallidum, Haemophilus ducreyi and herpes simplex virus. Overall, 57% of men and 80% of women had antibodies to HIV-1. The most frequent laboratory diagnoses were chancroid (27%), syphilis (19%) and genital herpes (19%) among men and syphilis (35%), genital herpes (23%) and chancroid (20%) among women. HIV-1 seroprevalence increased sharply over time among men but not among women. The clinical presentation of ulcers as well as laboratory diagnoses were similar in the HIV-1 seropositive and seronegative groups. The relative frequency of all laboratory diagnoses remained unchanged over time. HIV-1 seropositivity had no impact on ulcer healing. Advanced immunodeficiency was diagnosed among 12% of the HIV-1 seropositive patients and was significantly associated with increasing age and genital herpes.

AIDS-Related Opportunistic Infections↗

Antimicrobial resistance and serotypes of Shigella isolates in Kigali, Rwanda (1983 to 1993): increasing frequency of multiple resistance.

The serotype distribution and susceptibility to nine antibiotics was determined for 2491 Shigella isolates cultured in the medical laboratory of the Centre Hospitalier de Kigali, Rwanda, during 1983 to 1993. Overall, Shigella flexneri was the most frequent species, ranking before Shigella sonnei, Shigella boydii, and Shigella dysenteriae. However, the relative frequency of the different Shigella spp. showed an important variability over time. S flexneri increased from 40% in 1983 to 68% of the isolates in 1993 whereas S. dysenteriae Type 1 decreased gradually from 30 to 0.5% of the isolates in 1992. After the outbreak of severe civil unrest, which caused the displacement of many people to the capital, a new epidemic of dysentery started in the Kigali area and S. dysenteriae Type 1 accounted again for 24% of the isolates in 1993. In 1983, resistance to tetracycline, streptomycin, and sulfonamides was common among the endemic Shigella spp. Resistance to chloramphenicol was observed in 17% (30/182) of the isolates. Only 10% were resistant to ampicillin and an equal proportion to trimethoprim, whereas 5% of the isolates showed resistance to both products. By 1993, 66% (195/295) of the isolates were resistant to chloramphenicol (for comparison with 1983, p < 0.001), 70% (207/295) to ampicillin (p < 0.001), 67% to trimethoprim (p < 0.001), and 58% had combined resistance to the latter two drugs (p < 0.001). Resistance patterns differed strongly by species, S. flexneri being more frequently resistant than S. sonnei. In 1983, all S. dysenteriae Type 1 isolates were resistant to ampicillin, chloramphenicol, tetracycline, and sulfonamides. Trimethoprim resistance increased from 31% (25/80) in 1983 to 96% (26/27) of the isolates in 1986 (p < 0.001). After the introduction of nalidixic acid as an alternative for trimethoprim-sulfamethoxazole, trimethoprim resistance decreased to 87%, during 1987 to 1992, and subsequently to 68% of the isolates in 1993. However, 20% of the isolates became resistant to nalidixic acid in 1993. Ampicillin and trimethoprim-sulfamethoxazole are no longer useful for the empirical treatment of shigellosis in Rwanda.

Anti-Bacterial Agents↗

HIV infection as a risk factor for septic arthritis.

We prospectively studied the demographics, the clinical and diagnostic features, the HIV-1 serostatus and the therapeutic response for all new patients with septic arthritis (SA) admitted to the Department of Internal Medicine of the Centre Hospitalier de Kigali, Rwanda, over a 19 month period. SA was diagnosed in 24 patients (10 male, 14 female), of whom 19 (79%) were HIV-1 seropositive (HIVpos). Gonococcal arthritis was found in four patients, all HIVpos. Non-gonococcal bacterial arthritis was established in 16 patients, of whom 13 were HIVpos. Causative organisms involved in this group and the corresponding HIV-1 serostatus of the patients were: Staphylococcus aureus: 4; 2 HIVpos. 2 HIVneg: Streptococcus pneumoniae: 4; 4 HIVpos; Salmonella group B: 2; 2 HIVpos; Streptococcus group D: 1; 1 HIVpos; Klebsiella pneumoniae: 1; 1 HIVpos; undetermined: 4; 3 HIVpos; 1 HIVneg. Tuberculous arthritis was presumed in four patients, of whom two were HIVpos. HIV-1-associated SA had a classical acute presentation and an overall good prognosis Compared to a control group consisting of hospitalized patients with malaria as the sole diagnosis, patients with SA were more likely to be infected with HIV-1 (P = 0.005, or 6.3; 95% CI 1.7 22.2). Prevalence rate estimates of SA among HIVpos and HIVneg patients were 0.5 and 0.25%, respectively (P = 0.38). We conclude that HIV-1 infection appears as a risk factor for SA among patients hospitalized at the Centre Hospitalier de Kigali, but that SA cannot be used as a predictor for HIV-1 infection for hospitalized patients. SA occurs infrequently and may present at any stage of HIV-1 infection.

Adult↗

Increasing resistance of Neisseria gonorrhoeae in west and central Africa. Consequence on therapy of gonococcal infection.

BACKGROUND AND OBJECTIVES: Antimicrobial resistant strains of Neisseria gonorrhoeae have spread with remarkable rapidity in many African countries. Chromosomal resistance to penicillin, tetracycline, and thiamphenicol is frequent now, and reported prevalences of penicillinase-producing N. gonorrhoeae isolates vary between 15% and 80%. Plasmid-mediated tetracycline-resistant N. gonorrhoeae isolates have been observed in several African countries. GOALS: To characterize gonococcal isolates from three sites in West and Central Africa, to determine antimicrobial susceptibility patterns, to document the spread of plasmid-mediated resistance to penicillin and tetracycline in these three sites, and to discuss the consequences of rising antimicrobial resistance on the management of gonococcal infection in Africa. STUDY DESIGN: Over time, a total of 2,288 gonococcal isolates were obtained from Abidjan, Ivory Coast (1992-1993, n = 251), from Kigali, Rwanda (1988-1993, n = 952), and from Kinshasa, Zaire (1988-1990, n = 1,085). The isolates were characterized by auxotyping and serotyping. Plasmid-mediated resistance to penicillin and to tetracycline was determined. Antimicrobial susceptibility testing to ceftriaxone, ciprofloxacin, penicillin, spectinomycin, tetracycline, and thiamphenicol was performed with an agar dilution method. RESULTS: The prevalence of penicillinase-producing N. gonorrhoeae increased significantly over time from 44% to 57% in Kigali and remained stable at a high level in Abidjan (73%) and in Kinshasa (67%). The frequency of tetracycline-resistant N. gonorrhoeae increased significantly during the observation periods in all three sites: from 20% to 65% in Abidjan, from 0% to 64% in Kigali, and from 14% to 41% in Kinshasa. Chromosomal resistance to penicillin was common in Kigali and Kinshasa, and chromosomal resistance to tetracycline and thiamphenicol was frequent in all three sites. All gonococcal isolates were susceptible to ceftriaxone, ciprofloxacin, and spectinomycin. Prototrophic and proline requiring strains were predominant, and IA-6 was the most common serovar in the three sites. IB-specific serovars were more common among penicillinase-producing N. gonorrhoeae and IA-specific serovars were more frequent among tetracycline-resistant N. gonorrhoeae, but there was no evidence for a clonal spread of resistant strains. CONCLUSIONS: This study illustrates the high frequency of resistant gonococci in Africa and shows that tetracycline-resistant N. gonorrhoeae have become highly endemic in different geographic areas of the continent. The use of effective drugs is essential to reduce gonorrhea transmission. Surveillance of temporal changes in antimicrobial resistance in gonococcal strain populations should be part of sexually transmitted diseases control programs.

Cote d'Ivoire↗

Four years of natural history of HIV-1 infection in african women: a prospective cohort study in Kigali (Rwanda), 1988-1993.

Clinical features and mortality due to human immunodeficiency virus type-1 (HIV-1) infection in women are described as part of a prospective 4-year cohort study on perinatal transmission of HIV in Kigali, Rwanda. Two hundred fifteen HIV-seropositive (HIV+) and 216 HIV-seronegative (HIV-) pregnant women were enrolled at delivery between November 1988 and June 1989. Clinical information collected during systematic quarterly examinations was compared. HIV antibody tests were performed at delivery and CD4/CD8 lymphocyte counts at 15 days' postpartum. HIV--women who seroconverted during the follow-up period were excluded from the analysis of the comparison group starting at the date of seroconversion. At enrollment, all HIV+ women were asymptomatic for acquired immune deficiency syndrome (AIDS). Incidence of tuberculosis was 2.9 per 100 women-years (WY) after 4 years of follow-up in HIV+ women versus 0.2 per 100 WY among HIV- women (relative risk, 18.2; 95% confidence interval 2.4-137.0). Among HIV+ women, the incidence of AIDS (World Health Organization clinical AIDS definition) was 3.5 per 100 WY. The mortality rate was 4.4 per 100 WY among HIV+ women versus 0.5 per 100 WY among HIV- women. Clinical AIDS was present in only half of the fatalities. Tuberculosis was a major cause of morbidity and mortality in these HIV+ African women. An early diagnosis and an appropriate treatment or prevention of tuberculosis should improve the quality of life of HIV-infected patients in Africa.

Adult↗

Failure of treatment for chancroid in Rwanda is not related to human immunodeficiency virus infection: in vitro resistance of Haemophilus ducreyi to trimethoprim-sulfamethoxazole.

A comparative open study was performed to evaluate the efficacy of single doses of ciprofloxacin (500 mg) and trimethoprim-sulfamethoxazole (TMP-SMZ; 640 mg/3,200 mg) for the treatment of culture-proven chancroid. Clinical cure or improvement was observed 7 days after treatment in 32 (76.2%) of the 42 patients who received ciprofloxacin and 21 (52.5%) of the 40 patients who received TMP-SMZ (P = .04). Cultures for one (4.5%) of 22 patients not cured with ciprofloxacin and 16 (59.3%) of 27 patients not cured with TMP-SMZ were still positive for Haemophilus ducreyi 7 days after treatment (P < .001). Although 77 (71.3%) of the 108 patients tested were seropositive for HIV-1 antibody, HIV infection and the degree of CD4+ lymphocyte depletion had no effect on clinical and bacteriologic outcome. All isolates of H. ducreyi were highly susceptible to ciprofloxacin (MIC, 0.004-0.06 mg/L). In contrast, resistance to TMP-SMZ (MIC, > or = 4/76 micrograms/mL) was observed in 48.9% of isolates (22 of 45) and was significantly associated with treatment failure. Therefore, the administration of TMP-SMZ, in single or multiple doses, is no longer indicated for the treatment of chancroid in Rwanda.

Adult↗

Chronic diarrhea among adults in Kigali, Rwanda: association with bacterial enteropathogens, rectocolonic inflammation, and human immunodeficiency virus infection.

One hundred patients with chronic diarrhea were seen in the Department of Internal Medicine at the Centre Hospitalier de Kigali, Rwanda; stool and/or rectal swab culture was performed for these patients, and they underwent rectoscopy and serological testing for human immunodeficiency virus type 1 (HIV-1). Enteropathogenic bacteria were isolated from 39 (39%) of the patients: Shigella species (22 of 100 patients tested), non-typhi Salmonella (11/100), Aeromonas species (5/60), and Campylobacter species (4/60). Rectocolitis was seen in 70 (70%) of the patients. HIV-1 antibodies were detected in 82 (94%) of 87 patients tested. Cytomegalovirus was not found in rectal biopsy specimens from 29 patients. Entamoeba histolytica was detected in two of 31 rectal smears. Idiopathic ulcerative colitis was diagnosed for two HIV-1-seropositive patients. One or more AIDS-defining diseases were found in 32 (32%) of the patients, and 72 (72%) fulfilled the World Health Organization's clinical case definition criteria for AIDS. Chronic diarrhea, as seen in a hospital setting in a region highly endemic for HIV-1 infection, is strongly associated with HIV-1 infection, with rectocolonic inflammation, and with infection due to enteropathogenic bacteria.

Adult↗