Using PARP Inhibitors in Advanced Ovarian Cancer.

Poly(ADP-ribose) polymerase (PARP) proteins are used by cells in several DNA repair processes. PARP inhibition can result in preferential death of cancer cells when another mechanism for repairing DNA is defective. Two PARP inhibitors, olaparib and rucaparib, have been approved by the US Food and Drug Administration (FDA) for the treatment of recurrent, BRCA-associated ovarian cancer. More recently, these two and a third PARP inhibitor, niraparib, were approved by the FDA as maintenance therapy following platinum-based chemotherapy for recurrent ovarian cancer. This has caused a paradigm shift in disease management and a challenge for clinicians, who must decide how best to use these agents in individualized treatment. The oral formulation is attractive to patients, but adverse effects such as nausea and fatigue can impact quality of life. As clinicians become comfortable selecting PARP inhibitors and managing associated toxicities, future steps will be to investigate how to safely administer them in combination with other therapies.

[Immunomodulators for topical application to prevent and manage chronic adenoiditis in children].

The authors report the results of a study on the efficacy of topical application of the immunomodulator IRS 19 in children presenting with chronic adenoiditis and grade I-III hypertrophy of adenoid vegetation. The use of this preparation is shown to faster and more efficaciously normalize the volume of the lymphoid tissue than irrigation of the nasopharynx with saline solutions. Moreover, the treatment of chronic adenoiditis with IRS 19 promoted normalization of biocenosis of the nasopharyngeal secretion and significantly decreased the abundance of pathogenic microflora. Specifically, the overall frequency of exacerbations and the frequency of exacerbations of adenoiditis decreased three- and two-fold respectively while the duration of the disease shortened. It is recommended that the topical immunomodulator IRS 19 should be included in the programs of planned seasonal treatment of children suffering chronic adenoiditis (to be applied at least 2-3 times annually).

Nasopharyngeal carriage and susceptibility patterns of Streptococcus pneumoniae in Kumasi, Ghana.

UNLABELLED: Penicillin resistant Streptococcus pneunmoniae poses an increasing problem in paediatrics, particularly in less developed countries. Outside of South Africa, little is known about S. pneumoniae susceptibilities in Sub-Saharan Africa. The objective of this study was to determine the prevalence of pneumococcal colonization and antimicrobial susceptibility among children in urban Ghana. METHODS: Nasopharyngeal pneumococcal colonization was examined in 311 children attending a polyclinic for sick children and an immunization clinic in Kumasi, Ghana. Isolates were tested for antibiotic susceptibility to penicillin, tetracycline, erythromycin, chloramphenicol, cefuroxime, cefotaxime, ceftriaxone, and trimethoprim-sulfamethoxazole. RESULTS: Over half (51.4%) of subjects were colonized with S. pneumoniae and 17% of isolates were resistant to penicillin, all demonstrating intermediate resistance. S. pneumoniae strains were also frequently resistant to trimethoprim-sulfamethoxazole and tetracycline, less so to chloramphenicol and cefuroxime and were almost uniformly sensitive to cefotaxime, cefriaxone and erythromycin. CONCLUSIONS: Our study shows a high rate of pneumococcal nasopharyngeal colonization and a concerning level of penicillin resistance although at a less alarming rate than seen in some other countries. Multiple antimicrobial resistance was also noted especially among drugs readily available and commonly used. These data impact treatment choices in pneumococcal disease. Vaccine may play an important role in disease limitation. An effort to curtail the misuse of antibiotics, by prescription and otherwise, may prevent further increases in resistance rates.

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.