Erenumab prevents the occurrence of migraine attacks and not just migraine days: Post-hoc analyses of a phase III study.

BACKGROUND: This post-hoc analysis was conducted to evaluate the effect of erenumab on monthly migraine days, monthly migraine attacks, and attack duration in patients with episodic migraine to investigate whether erenumab actually prevents the occurrence of migraine attacks and/or shortens them. METHODS: We conducted a post-hoc analysis of the data from the STRIVE study, in 955 patients with episodic migraine. Relative changes from baseline to mean over months 4, 5 and 6 of the double-blind treatment phase in monthly migraine days, monthly migraine attacks and mean migraine attack duration were assessed. RESULTS: Erenumab reduced monthly migraine days and monthly migraine attacks compared with placebo in a similar way. Erenumab had only a minor impact on shortening the duration of migraine attacks. CONCLUSION: These post-hoc analyses demonstrate that the decrease in monthly migraine days by erenumab is mainly driven by a reduction in the frequency of monthly migraine attacks and to a much lesser extent by shortening the duration of migraine attacks.Trial registration: This study is registered at ClinicalTrials.gov (NCT02456740).

Pregnancy Outcomes among Women Receiving rVSVΔ-ZEBOV-GP Ebola Vaccine during the Sierra Leone Trial to Introduce a Vaccine against Ebola.

Little information exists regarding Ebola vaccine rVSVΔG-ZEBOV-GP and pregnancy. The Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE) randomized participants without blinding to immediate or deferred (18-24 weeks postenrollment) vaccination. Pregnancy was an exclusion criterion, but 84 women were inadvertently vaccinated in early pregnancy or became pregnant <60 days after vaccination or enrollment. Among immediate vaccinated women, 45% (14/31) reported pregnancy loss, compared with 33% (11/33) of unvaccinated women with contemporaneous pregnancies (relative risk 1.35, 95% CI 0.73-2.52). Pregnancy loss was similar among women with higher risk for vaccine viremia (conception before or <14 days after vaccination) (44% [4/9]) and women with lower risk (conception >15 days after vaccination) (45% [10/22]). No congenital anomalies were detected among 44 live-born infants examined. These data highlight the need for Ebola vaccination decisions to balance the possible risk for an adverse pregnancy outcome with the risk for Ebola exposure.

The Spectrum of Response to Erenumab in Patients With Episodic Migraine and Subgroup Analysis of Patients Achieving ≥50%, ≥75%, and 100% Response.

OBJECTIVE: To assess the efficacy of erenumab at the ≥50%, ≥75%, and 100% reduction in monthly migraine days (MMD) response thresholds, using data from the 6-month double-blind treatment phase (DBTP) of the Study to Evaluate the Efficacy and Safety of Erenumab in Migraine Prevention (STRIVE) pivotal clinical trial. METHODS: Enrolled patients with episodic migraine (EM; ≥4 MMD and <15 monthly headache days) were randomized (1:1:1) to erenumab 70 mg (n = 312), erenumab 140 mg (n = 318), or placebo (n = 316) once monthly. We determined the proportions of patients with ≥50%, ≥75% and 100% reduction in MMD over the last 3 months of the STRIVE DBTP (months 4 through 6) and conducted post hoc analyses to contextualize the treatment benefit in patient subgroups achieving, and not achieving, these response thresholds. Outcome measures included changes in MMD, acute migraine-specific medication days (MSMD), and patient-reported outcomes. RESULTS: The proportions of patients with a reduction in MMD from baseline were greater for erenumab than for placebo at all response thresholds. As previously reported for the ≥50% response threshold, 135/312 (43.3%) of patients on erenumab 70 mg and 159/318 (50.0%) on erenumab 140 mg responded, vs 84/316 (26.6%) for placebo. At months 4 through 6, 65/312 (20.8%) and 70/318 (22.0%) of those on erenumab 70 mg and erenumab 140 mg, respectively, achieved ≥75% reductions vs 25/316 (7.9%) on placebo. A reduction of 100% response, which required no migraine days over 3 consecutive months based on observed data, was achieved by 10/312 (3.2%) of patients treated with erenumab 70 mg and 16/318 (5.0%) for erenumab 140 mg, vs 9/316 (2.8%) for placebo. At all response thresholds, responders achieved numerically greater reductions in mean MMD and MSMD, and greater improvements in disability than did the overall population; importantly, these remarkable responses were noted early. Meanwhile, 60/312 (19.2%) and 53/318 (16.7%) patients on erenumab 70 and 140 mg, respectively, had no reduction in MMD from baseline in months 4 through 6, compared with 104/316 (32.9%) patients on placebo. CONCLUSIONS: The responses at the ≥50%, ≥75%, and 100% thresholds provide context for establishing realistic patient and physician expectations regarding the magnitude of treatment benefit that may be achieved by patients with EM responding to erenumab (STRIVE, NCT02456740).

Management of critical tracheal stenosis with a straw sized tube (Tritube): Case report.

Imminent upper airway obstruction due to life-threatening tracheal stenosis of any cause is a challenging situation. We present a challenging case of total thyroidectomy for a malignant, invasive, and highly vascularized thyroid carcinoma that has invaded the surrounding tissues, including the sternum and mediastinum, resulting in compression of the trachea with indentation. The patient presented with a significant symptomatic tracheal stenosis, the narrowest area of that was 4 mm. Airway management in such cases presents a particular challenge to the anesthesiologists, especially considering that the option of tracheostomy is very difficult most of the time due to the highly swollen thyroid and distorted anatomy. A meticulous history of the patient's illness had been taken, and a comprehensive preoperative evaluation was conducted, including construction of a 3D model airway, virtual endoscopy, and transnasal tracheoscopy. On the day of the surgery, the airway was managed through spontaneous respiration using intravenous anesthesia and the high-flow nasal oxygen (STRIVE-Hi) technique. It was then secured with intubation using a straw endotracheal tube (Tritube®) with an internal diameter (ID) of 2.4 mm and an outer diameter of 4.4 mm with the help of a fiberscope and D-MAC blade of a video laryngoscope. At the end of the procedure, the airway was checked with a fiber optic scope, which showed an improvement in the narrowed area. This enabled us to replace the Tritube with an adult cuffed ETT of size 6.5 mm ID, and the patient was transferred intubated to the surgical ICU. Two days later, the patient's tracheal diameter was evaluated with the help of a fiberoptic scope and extubated successfully in the operating theater.

The evolving role of enzalutamide on the treatment of prostate cancer.

The field of prostate cancer has witnessed incredible progress in the last decade, owing to the approval of multiple survival-prolonging treatments for metastatic castration-resistant prostate cancer (mCRPC). Enzalutamide is a nonsteroidal androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling axis. It has been approved for the treatment of mCRPC both in the postdocetaxel and in the chemotherapy-naive settings. We summarize the milestones in the development of enzalutamide in patients with prostate cancer. Special focus is placed on the results of the STRIVE Phase II clinical trial comparing head to head enzalutamide and bicalutamide in patients with nonmetastatic and mCRPC who have failed androgen deprivation and in other ongoing trials in the same setting and in earlier disease phases.

Influences of the Results from STRIVE Trial on the Combination Androgen Depletion Therapy for Advanced Prostate Cancer.

The clinical efficacy of combined therapy (CAB) has been clearly recognized by the results of the STRIVE trial. Although enzalutamide has shown a stronger effect on CRPC, bicultamide, a classical anti-androgen, has shown a significant effect. In addition, it can be deduced that CAB is a strong tool for hormone naïve advanced prostate cancer. Cost-effective evaluation for CAB with bicultamide or enzalutamide is warranted, especially for the resource-limited cohort.

Comparison of the application of high-flow nasal oxygen with two different oxygen concentrations in infant and child laryngotracheal surgery.

Background: This study aimed to compare the use of the STRIVE Hi technique with 70 and 100% oxygen concentrations in children with 1st or 2nd degree laryngeal obstruction undergoing suspension laryngoscopic surgery. Methods: Children aged 1 month to 6 years scheduled for suspension laryngoscopic surgery with spontaneous respiration were randomly divided into the 70% oxygen concentration group (HFNO70% group) and the 100% oxygen concentration group (HFNO100% group). The data recorded for all the patients included age and sex, comorbidities, preoperative physiological status, methods of induction and maintenance of anesthesia, course of the disease and surgical options, and duration of operation. The primary endpoint was the lowest oxygen saturations during the surgery. The secondary endpoints included the partial pressure of oxygen PaO2, the arterial pressure of carbon dioxide PaCO2, the peak transcutaneous carbon dioxide PtcCO2, and the incidence of desaturation (defined as SpO2 < 90%) or hypercarbia (PtcCO2 > 65 mmHg). Results: A total of 80 children with 1st or 2nd degree laryngeal obstruction were included in the analysis. The median [IQR (range)] duration of spontaneous ventilation using STRIVE Hi was 52.5 [40-60 (30-170)]min and 62.5 [45-81 (20-200)]min in the HFNO 70% and HFNO 100% groups, respectively (p = 0.99); the lowest oxygen saturation recorded during the operation was 97.8 ± 2.1% and 96.8 ± 2.5%, respectively (p = 0.053); the mean PaO2 at the end of surgery was 184.6 ± 56.3 mmHg and 315.2 ± 101.3 mmHg, respectively (p < 0.001); and the peak transcutaneous CO2 was 58.0 ± 13.0 mmHg and 60.4 ± 10.9 mmHg, respectively (p = 0.373), despite a long operation time. Conclusion: STRIVE Hi had a positive effect on children undergoing tubeless laryngeal surgery with spontaneous ventilation, and for children with 1st or 2nd degree laryngeal obstruction, there was no significant difference in maintaining the intraoperative oxygenation between the 70 and 100% oxygen concentration groups. The 100% oxygen concentration group showed significant hyperoxia, which has been proven to be associated with multiple organ damage. Using a relatively lower oxygen concentration of 70% can effectively reduce the hazards associated with hyperoxia compared to 100% oxygen concentration. Clinical trial registration: [www.chictr.org.cn], identifier [CHICTR2200064500].

Feasibility of Surgical Treatment for Laryngomalacia Using the Spontaneous Respiration Technique.

OBJECTIVES: In this study, we review our institutional experience with pediatric laryngomalacia (LM) and report our experiences of patients undergoing supraglottoplasty using the spontaneous respiration using intravenous anesthesia and high-flow nasal oxygen (STRIVE Hi) technique. METHODS: The medical records of 29 children with LM who visited Seoul National University Hospital between January 2017 and March 2019 were retrospectively reviewed. Surgical management was performed using the STRIVE Hi technique. Intraoperative findings and postoperative surgical outcomes, including complications and changes in symptoms and weight, were analyzed. RESULTS: Of the total study population of 29 subjects, 20 (68.9%) were female. The patients were divided according to the Onley classification as follows: type I (n=13, 44.8%), II (n=10, 34.5%), and III (n=6, 20.7%). Twenty-five patients (86.2%) had comorbidities. Seventeen patients (58.6%) underwent microlaryngobronchoscopy under STRIVE Hi anesthesia. Four patients with several desaturation events required rescue oxygenation by intermittent intubation and mask bagging during the STRIVE Hi technique. However, the procedure was completed in all patients without any severe adverse effects. Overall, 15 children (51.7%) underwent supraglottoplasty, of whom 14 (93.3%) showed symptom improvement, and their postoperative weight percentile significantly increased (P=0.026). One patient required tracheostomy immediately after supraglottoplasty due to associated neurological disease. CONCLUSION: The STRIVE Hi technique is feasible for supraglottoplasty in LM patients, while type III LM patients with micrognathia or glossoptosis may have a higher risk of requiring rescue oxygenation during the STRIVE Hi technique.