Cladribine tablets treatment for 2 years followed by 2 years' placebo treatment produced durable clinical benefits similar to 4 years of cladribine treatment with a low risk of severe lymphopenia or clinical worsening. No clinical improvement in efficacy was apparent following further treatment with cladribine tablets after the initial 2-year treatment period in this trial setting.

BackgroundThe CLARITY and CLARITY Extension studies demonstrated that treatment of relapsing–remitting multiple sclerosis (RRMS) with cladribine tablets (CT) results in significant clinical improvements, compared with placebo. This paper presents the key magnetic resonance imaging (MRI) findings from the CLARITY Extension study.MethodsPatients who received a cumulative dose of either CT 3.5 or 5.25 mg/kg in CLARITY were rerandomized to either placebo or CT 3.5 mg/kg in CLARITY Extension. Patients from the arm that received placebo in CLARITY were assigned to CT 3.5 mg/kg. MRI assessments were carried out when patients entered CLARITY Extension and after Weeks 24, 48, 72 and 96, and in a supplemental follow-up period.ResultsAt CLARITY Extension baseline, patients who received placebo during CLARITY had more T1 gadolinium-enhanced (Gd+) lesions than patients who received CT during CLARITY. These patients, who were then exposed to cladribine 3.5 mg/kg during the extension, experienced a 90.4% relative reduction (median difference −0.33, 97.5% confidence interval −0.33–0.00; p < 0.001) in T1 Gd+ lesions at the end of the extension compared with the end of CLARITY. Overall, the majority of patients in each treatment group remained free from T1 Gd+ lesions throughout CLARITY Extension. However, a small proportion of patients who were treated with cladribine in CLARITY and received placebo in CLARITY Extension showed evidence of increased MRI activity, and this was associated with a prolonged treatment gap between CLARITY and CLARITY Extension.ConclusionA 2-year treatment with CT 3.5 mg/kg has a durable effect on MRI outcomes in the majority of patients, an effect that was sustained in patients who were not retreated in the subsequent 2 years after initial treatment. ClinicalTrials.gov identifier: NCT00641537

Background Retaining participants in observational longitudinal studies following bariatric surgery is difficult yet critical because the retention rate affects interpretation and generalizability of results. Strategies for keeping participants involved in such studies are not commonly published. Objective To review LABS retention strategies and present the 24-month retention data Methods The LABS Consortium monitors an observational cohort study of 2458 adults enrolled prior to bariatric surgery at 10 centers within the United States (LABS-2). To maximize data completeness, the investigators developed retention strategies including flexible scheduling, a call protocol, reminder letters, abbreviated visit options, honoraria, travel reimbursement, providing research progress reports, laboratory results, newsletters, study website, and retention surveys. Strategies for locating participants included frequent updates of contact information, sending registered letters, and searching medical and public records. Results At 12 and 24 months, 2426 and 2405 participants remained active, with vital status known for 98.7% and 97.3% and weight obtained for 95.2% and 92.2% respectively. There were 148 missed visits (6.2%) at 24 months primarily because of inability to contact the participant. Only 15 (0.6%) active participants at 24-months missed all follow-up visits. Though 42 participants could not be located or contacted at 6 months, data were obtained for 23 (54.7%) of them at 12 months, and of the 52 participants who could not be located or contacted at 12 months; data were obtained for 18 (34.6%) at 24 months. Conclusion Longitudinal studies provide the ability to evaluate long-term effects of bariatric surgical procedures. The retention achieved in LABS is superior to many published reports but requires extensive effort and resources. This report identifies useful retention strategies. Further research is needed to identify the efficacy and cost effectiveness of specific retention strategies.

BACKGROUND Adverse intraoperative events (AIEs) during surgery are a well-known entity. A better understanding of the incidence of AIEs and their relationship with outcomes is helpful for surgeon preparation and preoperative patient counseling. The goals of this study are to describe the incidence of AIEs during bariatric surgery and examine their impact on major adverse complications. STUDY DESIGN The study included 5,882 subjects who had bariatric surgery in the Longitudinal Assessment of Bariatric Surgery study between March 2005 and April 2009. Prospectively collected AIEs included organ injuries, anesthesia-related events, anastomotic revisions, and equipment failure. The relationship between AIEs and a composite end point of 30-day major adverse complications (ie, death, venous thromboembolism, percutaneous, endoscopic, or operative reintervention and failure to be discharged from the hospital within 30 days from surgery) was evaluated using a multivariable relative risk model adjusting for factors known to influence their risk. RESULTS There were 1,608 laparoscopic adjusted gastric banding, 3,770 laparoscopic Roux-en-Y gastric bypass operations, and 504 open Roux-en-Y gastric bypass operations. Adverse intraoperative events occurred in 5% of the overall sample and were most frequent during open Roux-en-Y gastric bypass (7.3%), followed by laparoscopic Roux-en-Y gastric bypass (5.5%) and laparoscopic adjusted gastric banding (3%). The rate of composite end point was 8.8% in the AIE group compared with 3.9% among those without an AIE (p < 0.001). Multivariable analysis revealed that patients with an AIE were at 90% greater risk of composite complication than those without an event (relative risk = 1.90; 95% CI, 1.26–2.88; p = 0.002), independent of the type of procedure (open or laparoscopic). CONCLUSIONS Incidence of an AIE is not infrequent during bariatric surgery and is associated with much higher risk of major complication. Additional study is needed to assess the association between specific AIEs and short-term complications.

Background Anastomotic leak is one of the most serious complications following Roux-en-Y gastric bypass (RYGB). Objective To examine the relationship between technical factors and incidence of clinically relevant anastomotic leak following RYGB in Longitudinal Assessment of Bariatric Surgery (LABS). Setting Eleven bariatric centers in the United States, University and Private Practice. Methods Patient characteristics, technical factors of surgery, and postoperative outcomes were assessed by trained researchers using standardized protocols. Correlation of surgical factors of patients undergoing RYGB (n=4444) with the incidence of post-operative anastomotic leak was assessed by univariate chi-squared analysis. Results Forty-four participants (1.0%, 95%CI 0.7% to 1.3%) experienced a clinically relevant anastomotic leak. Of these, 39 (89%) underwent abdominal re-operation and 3 (7%) died. Technical factors associated with anastomotic leak were open surgery (p<0.0001), revision surgery (p<0.0001) and use of an abdominal drain (p=0.02). Provocative leak testing, method of gastrojejunostomy and use of fibrin sealant were not associated with anastomotic leak. Conclusions Anastomotic leak following RYGB was rare (1.0%). Most cases required reintervention, however, the majority (93%) recovered from this event. Open surgery, revision surgery and routine drain placement were associated with increased leak rate. Some of these findings may be due to differences in pre-operative patient risk.