Low-fluoroscopy atrial fibrillation ablation with contact force and ultrasound technologies: a learning curve.

BACKGROUND: Fluoroscopy exposure during catheter ablation is a health hazard to patients and operators. This study presents the results of implementing a low-fluoroscopy workflow using modern contact force (CF) technologies in paroxysmal atrial fibrillation (PAF) ablation. METHODS: A fluoroscopy reduction workflow was implemented and subsequent catheter ablations for PAF were evaluated. After vascular access with ultrasound guidance, a THERMOCOOL SMARTTOUCH® Catheter (ST) was advanced into the right atrium. The decapolar catheter was placed without fluoroscopy. A double-transseptal puncture was performed under intracardiac echocardiography guidance. ST and mapping catheters were advanced into the left atrium. A left atrial map was created, and pulmonary vein (PV) isolation was confirmed via entrance and exit block before and after the administration of isoproterenol or adenosine. RESULTS: Forty-three patients underwent PAF ablation with fluoroscopy reduction workflow (mean age: 66±9 years; 70% male), performed by five operators. Acute success rate (PV isolation) was 96.5% of PVs. One case of pericardial effusion, not requiring intervention, was the only acute complication. Mean procedure time was 217±42 minutes. Mean fluoroscopy time was 2.3±3.0 minutes, with 97.7% of patients having < 10 minutes and 86.0% having < 5 minutes. A significant downward trend over time was observed, suggesting a rapid learning curve for fluoroscopy reduction. Freedom from any atrial arrhythmias without reablation was 80.0% after a mean follow-up of 12±3 months. CONCLUSION: Low fluoroscopy time is achievable with CF technologies after a short learning curve, without compromising patient safety or effectiveness.

Erratum to: Safety and feasibility of oral immunotherapy to multiple allergens for food allergy.

[This corrects the article DOI: 10.1186/1710-1492-10-1.].

Recommendations from the Investigational New Drug/Investigational Device Exemption Task Force of the clInical and Translational Science Award Consortium: developing and implementing a sponsor-investigators training program.

OBJECTIVE: The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers. BACKGROUND: A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role. METHODS: The participants who developed the recommendations were representatives of institutions with IND/IDE support programs. Through an informal survey, the task force determined that a variety and mix of models are used to provide support for IND/IDE holders within CTSA institutions. In addition, a CTSA consortium-wide resources survey was used. The participants worked from the models and survey results to develop consensus recommendations to address institutional support, training content, and implementation. RECOMMENDATIONS: The CTSA IND/IDE Task Force recommendations are as follows: (1) Institutions should assess the scope of Food and Drug Administration-regulated research, perform a needs analysis, and provide resources to implement a suitable training program; (2) The model of training program should be tailored to each institution; (3) The training should specifically address the unique role of sponsor-investigators, and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution; and (4) Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

Research participant-centered outcomes at NIH-supported clinical research centers.

BACKGROUND: Although research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants' experiences. To address this, we developed and deployed a survey at 15 NIH-supported clinical research centers to assess participant-centered outcomes; we report responses from 4,961 participants. METHODS: Survey questions addressed core aspects of the research participants' experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses. RESULTS: Respondents broadly represented the research population in sex, race, and ethnicity. Seventy-three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R(2) = 0.80-0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%). CONCLUSIONS: Our survey demonstrates that a majority of participants at NIH-supported clinical research centers rate their research experience very positively and that participant-centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation.

Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab.

BACKGROUND: Up to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein. OBJECTIVE: To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously. METHODS: Participants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries. RESULTS: Twenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks. CONCLUSION: These phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.

Peanut oral immunotherapy results in increased antigen-induced regulatory T-cell function and hypomethylation of forkhead box protein 3 (FOXP3).

BACKGROUND: The mechanisms contributing to clinical immune tolerance remain incompletely understood. This study provides evidence for specific immune mechanisms that are associated with a model of operationally defined clinical tolerance. OBJECTIVE: Our overall objective was to study laboratory changes associated with clinical immune tolerance in antigen-induced T cells, basophils, and antibodies in subjects undergoing oral immunotherapy (OIT) for peanut allergy. METHODS: In a phase 1 single-site study, we studied participants (n = 23) undergoing peanut OIT and compared them with age-matched allergic control subjects (n = 20) undergoing standard of care (abstaining from peanut) for 24 months. Participants were operationally defined as clinically immune tolerant (IT) if they had no detectable allergic reactions to a peanut oral food challenge after 3 months of therapy withdrawal (IT, n = 7), whereas those who had an allergic reaction were categorized as nontolerant (NT; n = 13). RESULTS: Antibody and basophil activation measurements did not statistically differentiate between NT versus IT participants. However, T-cell function and demethylation of forkhead box protein 3 (FOXP3) CpG sites in antigen-induced regulatory T cells were significantly different between IT versus NT participants. When IT participants were withdrawn from peanut therapy for an additional 3 months (total of 6 months), only 3 participants remained classified as IT participants, and 4 participants regained sensitivity along with increased methylation of FOXP3 CpG sites in antigen-induced regulatory T cells. CONCLUSION: In summary, modifications at the DNA level of antigen-induced T-cell subsets might be predictive of a state of operationally defined clinical immune tolerance during peanut OIT.

Safety and feasibility of oral immunotherapy to multiple allergens for food allergy.

BACKGROUND: Thirty percent of children with food allergy are allergic to more than one food. Previous studies on oral immunotherapy (OIT) for food allergy have focused on the administration of a single allergen at the time. This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time. METHODS: Participants underwent double-blind placebo-controlled food challenges (DBPCFC) up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. Reactions during dose escalations and home dosing were recorded in a symptom diary. RESULTS: Forty participants met inclusion criteria on peanut DBPCFC. Of these, 15 were mono-allergic to peanut and 25 had additional food allergies. Rates of reaction per dose did not differ significantly between the two groups (median of 3.3% and 3.7% in multi and single OIT group, respectively; p = .31). In both groups, most reactions were mild but two severe reactions requiring epinephrine occurred in each group. Dose escalations progressed similarly in both groups although, per protocol design, those on multiple food took longer to reach equivalent doses per food (median +4 mo.; p < .0001). CONCLUSIONS: Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT. TRIAL REGISTRATION: Clinicaltrial.gov NCT01490177.