Enzalutamide Monotherapy vs Active Surveillance in Patients With Low-risk or Intermediate-risk Localized Prostate Cancer: The ENACT Randomized Clinical Trial.

Importance: There are few published studies prospectively assessing pharmacological interventions that may delay prostate cancer progression in patients undergoing active surveillance (AS). Objective: To compare the efficacy and safety of enzalutamide monotherapy plus AS vs AS alone in patients with low-risk or intermediate-risk prostate cancer. Design, Setting, and Participants: The ENACT study was a phase 2, open-label, randomized clinical trial conducted from June 2016 to August 2020 at 66 US and Canadian sites. Eligible patients were 18 years or older, had received a diagnosis of histologically proven low-risk or intermediate-risk localized prostate cancer within 6 months of screening, and were undergoing AS. Patients were monitored during 1 year of treatment and up to 2 years of follow-up. Data analysis was conducted in February 2021. Interventions: Randomized 1:1 to enzalutamide, 160 mg, monotherapy for 1 year or continued AS, as stratified by cancer risk and follow-up biopsy type. Main Outcomes and Measures: The primary end point was time to pathological or therapeutic prostate cancer progression (pathological, ≥1 increase in primary or secondary Gleason pattern or ≥15% increased cancer-positive cores; therapeutic, earliest occurrence of primary therapy for prostate cancer). Secondary end points included incidence of a negative biopsy result, percentage of cancer-positive cores, and incidence of a secondary rise in serum prostate-specific antigen (PSA) levels at 1 and 2 years, as well as time to PSA progression. Adverse events were monitored to assess safety. Results: A total of 114 patients were randomized to treatment with enzalutamide plus AS and 113 to AS alone; baseline characteristics were similar between treatment arms (mean [SD] age, 66.1 [7.8] years; 1 Asian individual [0.4%], 21 Black or African American individuals [9.3%], 1 Hispanic individual [0.4%], and 204 White individuals [89.9%]). Enzalutamide significantly reduced the risk of prostate cancer progression by 46% vs AS (hazard ratio, 0.54; 95% CI, 0.33-0.89; P = .02). Compared with AS, odds of a negative biopsy result were 3.5 times higher; there was a significant reduction in the percentage of cancer-positive cores and the odds of a secondary rise in serum PSA levels at 1 year with treatment with enzalutamide; no significant difference was observed at 2 years. Treatment with enzalutamide also significantly delayed PSA progression by 6 months vs AS (hazard ratio, 0.71; 95% CI, 0.53-0.97; P = .03). The most commonly reported adverse events during enzalutamide treatment were fatigue (62 [55.4%]) and gynecomastia (41 [36.6%]). Three patients in the enzalutamide arm died; none were receiving the study drug at the time of death. No deaths were considered treatment-related. Conclusions and Relevance: The results of this randomized clinical trial suggest that enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer. Enzalutamide may provide an alternative treatment option for patients undergoing AS. Trial Registration: ClinicalTrials.gov Identifier: NCT02799745.

Acoustics of Emotional Prosody Produced by Prelingually Deaf Children With Cochlear Implants.

Purpose: Cochlear implants (CIs) provide reasonable levels of speech recognition quietly, but voice pitch perception is severely impaired in CI users. The central question addressed here relates to how access to acoustic input pre-implantation influences vocal emotion production by individuals with CIs. The objective of this study was to compare acoustic characteristics of vocal emotions produced by prelingually deaf school-aged children with cochlear implants (CCIs) who were implanted at the age of 2 and had no usable hearing before implantation with those produced by children with normal hearing (CNH), adults with normal hearing (ANH), and postlingually deaf adults with cochlear implants (ACI) who developed with good access to acoustic information prior to losing their hearing and receiving a CI. Method: A set of 20 sentences without lexically based emotional information was recorded by 13 CCI, 9 CNH, 9 ANH, and 10 ACI, each with a happy emotion and a sad emotion, without training or guidance. The sentences were analyzed for primary acoustic characteristics of the productions. Results: Significant effects of Emotion were observed in all acoustic features analyzed (mean voice pitch, standard deviation of voice pitch, intensity, duration, and spectral centroid). ACI and ANH did not differ in any of the analyses. Of the four groups, CCI produced the smallest acoustic contrasts between the emotions in voice pitch and emotions in its standard deviation. Effects of developmental age (highly correlated with the duration of device experience) and age at implantation (moderately correlated with duration of device experience) were observed, and interactions with the children's sex were also observed. Conclusion: Although prelingually deaf CCI and postlingually deaf ACI are listening to similar degraded speech and show similar deficits in vocal emotion perception, these groups are distinct in their productions of contrastive vocal emotions. The results underscore the importance of access to acoustic hearing in early childhood for the production of speech prosody and also suggest the need for a greater role of speech therapy in this area.

Results of endovascular therapy and aortobifemoral grafting for Transatlantic Inter-Society type C and D aortoiliac occlusive disease.

OBJECTIVE: The purpose of this study was to compare the outcomes of aortoiliac stenting (AIS) to those of aortobifemoral grafting (ABF) for patients with TransAtlantic Inter-Society Consensus (TASCII) C and D aortoiliac occlusive disease. METHODS: From 1998 to 2007, 32 patients underwent ABF and 40 patients underwent AIS. Kaplan-Meier estimates for patency were used. RESULTS: Patients undergoing AIS were older (66.6 years ABF vs 59.2 years AIS; P=.006). The ABF group had simultaneous profundoplasty (n = 8) and femoral-popliteal graft (n =1). Six patients had treatment for concomitant infrainguinal disease at the time of AIS. There was no mortality in either group. Average hospital stay in the ABF group was 7 +/- 2 days and 1 +/- 0.3 days for AIS (P = .0001). Pulmonary complications predominated in the ABF group (13%). Four patients in the AIS group (10%) developed intraprocedural complications. Primary patency at 48 months was 69 +/- .12% for AIS and 93 +/- .07% for ABF (P = .013). There was a significant increase in ankle-brachial indices after revascularization in both groups. CONCLUSIONS: TASC type C and D lesions can be treated with either ABF or AIS with satisfactory results. Compared with ABF, AIS is associated with decreased primary patency, decreased perioperative morbidity, and shorter hospital stay.