Fluoride supplements and fluorosis: a meta-analysis

This paper presents a systematic review of the dental literature that was carried out to investigate whether the regular use of fluoride supplements in non-fluoridated communities during the period of tooth development increases the risk of dental fluorosis. A MEDLINE search was organized for all documents published, in English, between January 1966 and September 1997 using the following key words: fluorosis, dental, fluoride, fluoride supplement or supplements, drop or drops, and tablet or tablets. Twenty-four studies that assessed the development of dental fluorosis in children who had used fluoride supplements earlier in their life were included in this review. Of the 24 studies, 10 were crosssectional/case control studies and four were follow-up studies. These studies had data that allowed a quantitative estimation of the risk of developing dental fluorosis in users of fluoride supplements. The other 10 studies were excluded because they either did not present enough data or had other methodological problems. A qualitative review of the studies found a consistent and strong association between the use of fluoride supplements and dental fluorosis. The meta-analyses of the cross-sectional/case-control studies estimated that the odds ratio of dental fluorosis in users of fluoride supplements compared with non-users ranged between 2.4 and 2.6. The meta-analyses of the follow-up studies estimated that the relative risk in long-term users was between 5.5 and 12.2. This review confirmed that in non-fluoridated communities the use of fluoride supplements during the first 6 years of life is associated with a significant increase in the risk of developing dental fluorosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75253/1/j.1600-0528.1999.tb01991.x.pd

Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort

Background: Apalutamide is a potent androgen receptor (AR) antagonist that targets the AR ligand-binding domain and prevents AR nuclear translocation, DNA binding, and transcription of AR gene targets. Objective: To evaluate the activity and safety of apalutamide in patients with high-risk nonmetastatic castration-resistant prostate cancer (nmCRPC). Design, setting, and participants We conducted a multicenter phase 2 study of nmCRPC patients with a high risk for progression (prostate-specific antigen [PSA] ≥8 ng/ml or PSA doubling time [PSA DT] ≤10 mo). Intervention Patients received 240 mg/d apalutamide while continuing on androgen-deprivation therapy. Outcome measurements and statistical analysis Primary end point was 12-wk PSA response (Prostate Cancer Working Group 2 criteria). Secondary end points included safety, time to PSA progression (TTPP), and metastasis-free survival (MFS). Results and limitations A total of 51 patients were enrolled; four patients with metastatic disease were excluded from the efficacy analysis. Patient characteristics included median age, 71 yr; Eastern Cooperative Oncology Group performance status 0 (76%); Gleason score ≤ 7 (57%); median PSA 10.7 ng/ml; and PSA DT ≤10 mo (45%). At median follow-up of 28.0 mo, 18 patients (35%) remained in the study. Overall, 89% of patients had ≥50% PSA decline at 12 wk. Median TTPP was 24.0 mo (95% confidence interval [CI], 16.3 mo–not reached [NR]); median MFS was NR (95% CI, 33.4 mo–NR). Most of the patients discontinued study treatment (n = 33) due to disease progression (n = 11 [22%]) or adverse events (AEs) (n = 9 [18%]). The most common AE was fatigue (any grade, n = 31 [61%]) although grade ≥3 fatigue was uncommon (n = 2 [4%]). These represent the first apalutamide nmCRPC patient clinical data. Conclusions: In high-risk nmCRPC patients, apalutamide was safe with robust activity based on durable PSA responses and disease control. Patient summary Antitumor activity and the safety of apalutamide in patients with nonmetastatic castration-resistant prostate cancer support continued development in this setting. Trial registration ClinicalTrials.gov identifier NCT0117189