Radiofrequency ablation for the treatment of weight regain after Roux-en-Y gastric bypass surgery.

BACKGROUND AND AIMS: Roux-en-Y gastric bypass (RYGB) surgery is an established modality for the treatment of morbid obesity. However, approximately one-quarter of patients experience weight regain after initially successful weight loss. Endoscopic therapy targeting the gastric remnant pouch represents a novel potential strategy to re-induce weight loss in this population. We performed a pilot trial of radiofrequency ablation (RFA) of the gastric remnant pouch after RYGB to determine feasibility, safety, and efficacy for weight loss. METHODS: We identified patients who had undergone RYGB, achieved >40% excess body weight loss (EBWL), and then regained >25% of lost weight. RFA was applied to the gastrojejunal anastomosis and the entire surface area of the gastric remnant pouch. Treatment was repeated at 4 and 8 months if patients did not meet specified weight loss targets. Weekly weights were obtained for 12 months. The primary efficacy outcome was percent EBWL at 12 months, compared with baseline. RESULTS: Twenty-five patients were enrolled at 4 centers. Mean (± standard deviation [SD]) age was 45.4 ± 9.1 years, and 84% (21/25) were female. Mean (± SD) baseline body mass index was 40.2 ± 7.8. Twenty-two of 25 patients completed 12 months of follow-up. At 12 months, median (± SD) EBWL was 18.4% (interquartile ratio 10.8, 33.7; P < .0001). Significant weight loss was seen at 3.5 months (P < .0001) and at 7.5 months (P < .0001), with a significant trend for continued weight loss over the 12-month period (P = .013). Two patients had serious adverse events requiring hospitalization. CONCLUSIONS: RFA of the gastric remnant pouch in patients with weight regain after RYGB resulted in significant reductions in excess body weight with an acceptable safety profile. Continued weight loss was observed after each RFA treatment. Further clinical trials in well-selected populations are warranted to determine the optimal number and frequency of RFA treatments and to assess durability of weight loss. (Clinical trial registration number: NCT01910688.).

Sacral nerve stimulation for intractable constipation.

OBJECTIVE: Traditional surgical procedures for intractable idiopathic constipation are associated with a variable outcome and substantial morbidity. The symptomatic response, physiological effect and effect on quality of life of sacral nerve stimulation (SNS) were evaluated in patients with constipation (slow transit and normal transit with impaired evacuation). METHODS: In a prospective study at five European sites patients who failed conservative treatment underwent 21 days test stimulation. Patients with >50% improvement in symptoms underwent permanent neurostimulator implantation. Primary end points were increased defecation frequency, decreased straining and decreased sensation of incomplete evacuation. RESULTS: 62 patients (55 female, median age 40 years) underwent test stimulation, of whom 45 (73%) proceeded to chronic stimulation. 39 (87%) of these 45 patients achieved treatment success. After a median 28 (range 1-55) months follow-up, defecation frequency increased from 2.3 to 6.6 evacuations per week (p<0.001). Days per week with evacuation increased from 2.3 to 4.8 (p<0.001). There was a decrease in time spent toileting (10.5 to 5.7 min, p=0.001), straining (75-46% of successful evacuations, p<0.001), perception of incomplete evacuation (71.5-46% of successful evacuations, p<0.001) and subjective rating of abdominal pain and bloating (p<0.001). Cleveland Clinic constipation score (0=no to 30=severe constipation) decreased from 18 to 10 (p<0.001). Visual analogue scale (VAS) score (0=severe to 100=no symptoms) increased from 8 to 66 (p<0.001). Patients with slow and normal transit benefited. Quality of life significantly improved. Colonic transit normalised in half of those with baseline slow transit (p=0.014). CONCLUSION: SNS is effective in the treatment of idiopathic slow and normal transit constipation resistant to conservative treatment. Clinical Trial Number NCT00200005.

Design effects for highly clustered count data with varying length of follow-up--applying to the analysis of ICD shocks.

Highly clustered count data are commonly seen in medical device clinical studies such as cardiac rhythm management. For instance, anti-arrhythmia shocks delivered from an implantable cardioverter-defibrillator (ICD) often occur as "storms", i.e., multiple shocks within a short period of time. There are unique challenges in designing and analyzing clinical studies with such response data. In general, there is less amount of data information available when events occur as "storms" as compared to independent events, and the efficiency loss may be substantial in practice. In addition, event incidences of subjects may be highly unbalanced and length of follow-up may vary from subject to subject. In this paper, the design effect for such highly clustered and unbalanced count data is studied. Varying length of subject follow-up is taken into account by the use of a random variable that may depend on external covariates. Sample size adjustment for event correlation and imbalance is discussed. The practical application of the strategy is illustrated through a clinical study of ICD shock therapy.

A comparison of empiric to physician-tailored programming of implantable cardioverter-defibrillators: results from the prospective randomized multicenter EMPIRIC trial.

OBJECTIVES: The purpose of this randomized study was to determine whether a strategically chosen standardized set of programmable settings is at least as effective as physician-tailored choices, as measured by the shock-related morbidity of implantable cardioverter-defibrillator (ICD) therapy. BACKGROUND: Programming of ventricular tachyarrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF]) detection and therapy for ICDs is complex, requires many choices by highly trained physicians, and directly influences the frequency of shocks and patient morbidity. METHODS: A total of 900 ICD patients were randomly assigned to standardized (EMPIRIC, n = 445) or physician-tailored (TAILORED, n = 455) VT/VF programming and followed for 1 year. RESULTS: The primary end point was met: the adjusted percentages of both VT/VF (22.3% vs. 28.7%) and supraventricular tachycardia or other non-VT/VF event episodes (11.9% vs. 26.1%) that resulted in a shock were non-inferior and lower in the EMPIRIC arm compared to the TAILORED arm. The time to first all-cause shock was non-inferior in the EMPIRIC arm (hazard ratio = 0.95, 90% confidence interval 0.74 to 1.23, non-inferiority p = 0.0016). The EMPIRIC trial had a significant reduction of patients with 5 or more shocks for all-cause (3.8% vs. 7.0%, p = 0.039) and true VT/VF (0.9% vs. 3.3%, p = 0.018). There were no significant differences in total mortality, syncope, emergency room visits, or unscheduled outpatient visits. Unscheduled hospitalizations occurred significantly less often (p = 0.001) in the EMPIRIC arm. CONCLUSIONS: Standardized empiric ICD programming for VT/VF settings is at least as effective as patient-specific, physician-tailored programming, as measured by many clinical outcomes. Simplified and pre-specified ICD programming is possible without an increase in shock-related morbidity.

Marginalized binary mixed-effects models with covariate-dependent random effects and likelihood inference.

Marginal models and conditional mixed-effects models are commonly used for clustered binary data. However, regression parameters and predictions in nonlinear mixed-effects models usually do not have a direct marginal interpretation, because the conditional functional form does not carry over to the margin. Because both marginal and conditional inferences are of interest, a unified approach is attractive. To this end, we investigate a parameterization of generalized linear mixed models with a structured random-intercept distribution that matches the conditional and marginal shapes. We model the marginal mean of response distribution and select the distribution of the random intercept to produce the match and also to model covariate-dependent random effects. We discuss the relation between this approach and some existing models and compare the approaches on two datasets.

Imiquimod 5-percent cream does not alter the natural history of recurrent herpes genitalis: a phase II, randomized, double-blind, placebo-controlled study.

Present strategies for control of herpes genitalis recurrences require multiple daily doses of antiviral medication. Imiquimod, an immune response modifier, induces alpha interferon and interleukin-12; application in the presence of local herpes antigens during a recurrence may augment herpes simplex virus (HSV)-specific cell-mediated immunity. To test this theory, we performed a randomized, double-blind, placebo-controlled study of imiquimod 5% cream to assess safety and efficacy for decreasing recurrences. Patients with six or more recurrences of herpes genitalis per year applied study cream (imiquimod or placebo) to lesions one, two, or three times per week for 3 weeks for each recurrence during a 16-week treatment period. This was followed by a 16-week observation period. Of 124 patients randomized to the study, 103 completed the treatment period and 93 completed the observation period. The median times to first genital herpes recurrence were 53 days for those receiving placebo (n = 30) and 54, 60, and 64 days for those receiving imiquimod one time per week (n = 34), two times per week (n = 32), and three times per week (n = 28), respectively. The median annualized recurrence rates during the treatment period were 3.8, 4.9, 3.2, and 3.1, respectively. There were no statistically significant differences in the time to first recurrence or in the annualized recurrence rate between the imiquimod and placebo groups in either the treatment or the observation period. A trend in increased rates of local adverse events at the application site and a delay in lesion healing with more frequent dosing suggested a pharmacologic effect. Although clinical efficacy has been observed for imiquimod in other conditions in which a TH1-type immune response may be beneficial, including other viral infections such as those caused by human papillomavirus, no apparent effect on the short-term natural history of herpes genitalis recurrences was observed.