Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension.

BACKGROUNDS AND AIMS: This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis. METHODS: Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates. RESULTS: This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently. CONCLUSIONS: Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.

Long-Term Efficacy and Safety of Ozanimod in Moderately to Severely Active Ulcerative Colitis: Results From the Open-Label Extension of the Randomized, Phase 2 TOUCHSTONE Study.

BACKGROUND AND AIMS: This analysis examined the long-term safety and efficacy of ozanimod in patients with moderately to severely active ulcerative colitis [UC] with ≥ 4 years of follow-up in the phase 2 TOUCHSTONE open-label extension [OLE]. METHODS: Patients receiving placebo or ozanimod HCl 0.5 mg or 1 mg during the double-blind period could enter the OLE [ozanimod HCl 1 mg daily]. Partial Mayo score [pMS] clinical response and remission were assessed through OLE week 200 and summarized descriptively using observed cases [OC] and non-responder imputation [NRI]. Endoscopy was required at OLE week 56 and the end of treatment. Parameters associated with endoscopy were summarized at weeks 56 and 104 [OC], and week 56 [NRI]. C-reactive protein and faecal calprotectin were assessed. Adverse events were monitored throughout the study. RESULTS: Of 197 patients receiving double-blind treatment, 170 entered the OLE. Discontinuation rates were 28% at year 1 and 15-18% annually through year 4. Partial Mayo measures indicated clinical response and remission rates at OLE week 200 of 93.3% and 82.7%, respectively, using OC and 41% and 37% with the more conservative NRI analysis. At weeks 56 and 104, respectively, histological remission rates were 46.3% and 38.5%, and endoscopic improvement rates were 46.4% and 46.5% [OC]. No new safety signals were identified during ≥ 4 years of follow-up. CONCLUSIONS: There was a high rate of continued study participation and long-term benefit with ozanimod HCl 1 mg daily based on clinical, histological and biomarker measures in patients with moderately to severely active UC in the TOUCHSTONE OLE. [NCT02531126].

Long-term Safety of Sunitinib in Metastatic Renal Cell Carcinoma.

BACKGROUND: Metastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr. OBJECTIVE: To analyze long-term safety with sunitinib in mRCC patients. DESIGN, SETTING, AND PARTICIPANTS: Data were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g., cytokine refractory or treatment-naïve). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Interval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment. RESULTS AND LIMITATIONS: Among long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0-<6 mo to 42% at 5-<6 yr and by cumulative analysis from 14% at 0-<1 yr to 36% over 6 yr. Grade 3/4 TRAEs in long-term patients peaked during the first year and then steadily decreased. The overall population displayed only minor differences from long-term patients, with no clinically significant differences between grade ≥3 TRAE profiles (<5% difference in incidence rates at all intervals). Limitations included retrospective design, assessment variability, lack of pharmacokinetic data, and absence of baseline characteristics for long-term patients. CONCLUSIONS: Prolonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative. PATIENT SUMMARY: More than 800 mRCC patients received sunitinib for between 2 and 6 yr without experiencing new or more severe treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib treatment for as long as patients continue to derive clinical benefit, without untoward additional risk.

Patient perception of the role of anesthesiologists: a perspective from the Caribbean.

STUDY OBJECTIVE: To assess patients' perception of the role of an anesthesiologist in a Caribbean country. DESIGN: Self-administered structured questionnaire evaluation. SETTING: Preoperative waiting rooms of three tertiary-care teaching hospitals: Port of Spain General Hospital, Eric Williams Medical Sciences Complex, and San Fernando General Hospital, Trinidad. PATIENTS: 424 adult surgical patients awaiting elective surgery. INTERVENTIONS: None. MEASUREMENTS: A questionnaire was devised to test the knowledge of the respondents regarding the job description, attitudes, and various roles of anesthesiologists in the hospital. MAIN RESULTS: 371 completed responses were obtained for analysis. One tenth of the respondents did not know who an anesthesiologist was and 59% of them knew that an anesthesiologist was a doctor; there was a statistically significant association of the educational level of the respondent and this response. Of the respondents, 70% felt that the anesthesiologists were easy to talk to and pleasant by the bedside; 46% responded that the anesthesiologists did not discuss the complications and side effects of drugs before the procedure; 5% considered the anesthesiologists as more important than the surgeon, and 59% considered both equally important. Only 19% responded that they knew that the anesthesiologists had a role in the intensive care unit. CONCLUSIONS: Patients still have inadequate knowledge regarding anesthesiologists and their different roles in hospitals.

Evaluation of the utilization of the preanaesthetic clinics in a university teaching hospital.

BACKGROUND: Dedicated out-patient preanaesthetic clinics are relatively recent phenomenon and information is sparse from developing world. This study attempted to evaluate the utilization of adult and paediatric preanaesthetic clinics and its impact on the cancellations of surgery in Trinidad. METHODS: All patients scheduled to have elective surgery during the period of twelve weeks were enrolled for prospective collection of data including demographics, the admitting diagnoses, surgical procedure, category of surgery and specialty, and the patients' attendance to preanaesthetic clinics. Cancellations on the day of surgery along with reasons were recorded. The difference between patients who attended and did not attend the clinic was analysed. RESULTS: Of 424 patients scheduled for procedures during the study period, 213 were adults and 211 were children. Overall 39% of adults and 46% of the children scheduled for surgery had previously attended the preanaesthetic clinic. Among adults, general surgery patients were the largest majority to attend the preanaesthetic clinic. The paediatric preanaesthetic clinic was mostly utilized by paediatric general surgery. Overall 30% of procedures in adults and 26% of those in children were cancelled. There was a statistically significant difference in cancellations between patients who attended and did not attend the preanaesthetic clinic (p = 0.004). There was a 52% more chance of the procedure getting cancelled if the patient did not attend the clinic. CONCLUSION: The study highlights the inadequate use of the preanaesthetic clinics and the impact of the clinics on last-minute cancellations.

Performance of a pediatric ambulatory anesthesia program--a developing country experience.

BACKGROUND: The aim of this study was to evaluate the performance of a pediatric ambulatory anesthesia program in a tertiary care teaching hospital in a developing country. METHODS: Data on all pediatric patients (<16 years of age) scheduled to have elective day-care surgery during a 1 year period from January 1999 to December 1999 were collected retrospectively. An audit form was used to determine the specialty of the procedures, anesthesia techniques, postoperative analgesia, perioperative complications, unplanned admissions and outcomes with respect to morbidity and mortality. RESULTS: A total of 763 pediatric ambulatory surgical procedures were performed during the year of 1999. The procedures included general surgery, ENT, orthopedic and plastic surgery. The most common procedure was inguinal hernia repair followed by umbilical hernia repair, adenotonsillectomy and circumcision and 96% of the patients had general anesthesia. There were only three unplanned admissions (0.4%); one for a surgical reason and two for anesthetic reasons. There was no serious morbidity or mortality in any patient. CONCLUSIONS: Performance of pediatric day-care anesthesia has been good in our day-care unit and we have a successful ambulatory surgery program, despite the limitations of a developing country.