This study was designed to characterize a collection of 60 enteropathogenic Escherichia coli (EPEC) isolates from diarrheic feces of patients in the Ribeirão Preto metropolitan area regarding different phenotypic and molecular features. We examined antibiotic resistance profiles, occurrence of virulence factors‐encoding genes, intimin subtypes and the correlation of serotypes among typical (tEPEC) and atypical (aEPEC) EPEC isolates. The results demonstrated that atypical EPEC was more heterogeneous than typical EPEC concerning the characteristics investigated and 45.2% do not belong to classical EPEC serogroups. Intimin subtype β was the most frequent among the EPEC isolates (46.7%), being detected in both tEPEC and aEPEC. The majority of aEPEC isolates presented localized adherence‐like (LAL) pattern to HEp‐2 cells, although aEPEC isolates displaying diffuse adherence (DA) or non‐adherent were also detected. High prevalence of antimicrobial resistance was found for ampicillin, cephalothin, sulfonamide and tetracycline. In general, tEPEC isolates were more resistant to the antimicrobials tested than aEPEC isolates. 相似文献
Cerebral Palsy motor disorder triggers orthopedic complications. These complications do develop by themselves and gradually degrade the motor function. The functioning of the ventilatory pump is no exception to this process. Other orthopedic impairments are impacting more indirectly ventilation. Some orthopedic treatments used for PC people are likely to worsen this clinical situation, temporarily or more permanently. Any therapeutic intervention must include two essential points: acting previously to realign posture and considering interactions of treatments on different functions. 相似文献
BackgroundFOLFIRI (irinotecan, 5-fluorouracil, and leucovorin) + aflibercept improves median overall survival (OS) and progression-free survival (PFS) in patients with previously treated metastatic colorectal cancer (mCRC). Our aim was to investigate efficacy and tolerability of this combination in the first line.Patients and MethodsPatients with untreated documented mCRC received aflibercept plus FOLFIRI every 14 days until progression or unacceptable toxicity in an open, phase II single-arm, multicenter trial. The primary endpoint was the 6-month PFS rate. Secondary endpoints were OS and tolerability. A 2-step Simon design was used with H0: 55% and H1= 75%. Data were analyzed in intention to treat.ResultsForty-one patients were included, and 40 were analyzed (1 consent withdrawal) in 9 French centers between October 2014 and February 2017. The median age was 65 years (range, 46-81 years), 55% had ≥ 2 metastatic sites, and 50% and 15% had RAS and BRAF mutations, respectively. Twenty-two (54.5%; 95% confidence interval, 38.9%-68.5%) patients were alive and non-progressive at 6 months. FOLFIRI + aflibercept was considered ineffective, resulting in the cessation of inclusions. The median follow-up was 34 months. The overall response rate was 55%, and the disease control rate was 80%. The median duration of treatment was 5.3 months; the median PFS and OS were 8.2 and 18.6 months, respectively. Grade 3 to 4 adverse events were mainly gastrointestinal (47.5%) and vascular (32.5%). Of the patients, 87.5% had at least 1 dose modification.ConclusionAlthough the primary objective was not met, first-line FOLFIRI + aflibercept for mCRC leads to median PFS and OS close to those reported with classical doublet and targeted agents, but with significant toxicities needing dose reduction. 相似文献
Background/ObjectivesPolypharmacy and multimorbidity is a threat to older people; hence, listing approaches should support physicians to optimize medication. The FORTA (Fit fOR The Aged) classification of drug appropriateness for older people provides positive or negative labels: A (A-bsolutely), B (B-eneficial), C (C-areful), and D (D-on't). Based on these categories, FORTA-labeled drug lists were developed in 7 European countries or regions; the same approach was used to develop a U.S.-FORTA List reflecting the country-specific availability and usage of drugs.Design/SettingA 2-step Delphi-type approach was employed to add, remove, or relabel drugs from the listing proposal and to add or remove new indications. The proposal utilized the European (EURO)-FORTA list as template.ParticipantsEight US-based geriatricians/pharmacists served as raters. Measurements: Raters gave recommendations and comments on the list items.ResultsThe first U.S.-FORTA List contains 273 items aligned to 27 main indication groups; 30 drugs and drug groups were added, and 23 removed as being unavailable in the United States. The highest percentage of changes in FORTA labels as compared to the EURO-FORTA List occurred for sleep disorders associated with dementia (40%). In 8 indications, the labels for 11 items were different from the proposal. Thus, for the majority of the items (n = 232, 95.5%), the proposals were accepted by the US raters. Only 16 (6.6%) of the proposed items (n = 243) had to be re-evaluated in the second round as a result of inconsistent rating in the first round.Conclusions and ImplicationsThe U.S.-FORTA List addresses the appropriateness of drugs for older people in the United States reflecting country-specific availability, usage, and expert rating. As shown for the FORTA list in Europe, this listing approach is among the few that are clinically validated and improve well-being and geriatric outcomes. The U.S.-FORTA List now largely enhances the global availability of this approach. 相似文献
Introduction: Tamoxifen dominates the anti-estrogenic therapy in the early and metastatic breast cancer setting. Tamoxifen has a complex metabolism, being mainly metabolized by CYP2D6 into its 30–100 times more potent metabolite, endoxifen. Recently, a phase I study in which endoxifen as an orally z-endoxifen hydrochloride has been successfully evaluated.
Areas covered: the principal pharmacogenetic and non-genetic differences in the pharmacology of tamoxifen and endoxifen are evaluated. To this end, references from PubMed, Embase or Web of Science, among others, were reviewed As non-genetic factors, important differences and similarities such age, or adherence to tamoxifen therapy are comprehensively illustrated. Additionally, since CYP2D6 genotypes are considered the main limitation of tamoxifen, many studies have investigated the association between the worsened clinical outcomes in patients with non-functional CYP2D6 genotypes. In this review, an overview of the research on this field is presented. Also, a summary describing the literature about individualizing tamoxifen therapy with endoxifen concentrations and its limitations is listed.
Expert opinion: z-endoxifen hydrochloride is only investigated in the metastatic setting, still more research is required before its place in therapeutics is known. Similarly, monitoring tamoxifen efficacy based on endoxifen concentrations might not be overall recommended due to the limited evidence available. 相似文献