Publications

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is associated with significant morbidity and mortality. Bedaquiline is the first drug approved for treating MDR-TB.

OBJECTIVES: We performed a systematic review and meta-analysis to summarize the totality of all available evidence on the efficacy of bedaquiline for the management of MDR-TB.

MATERIALS AND METHODS: We searched the following PubMed and Cochrane Registry of Clinical Trials. Randomized controlled trials (RCTs) with a parallel design comparing bedaquiline versus any treatment for the management of MDR-TB in adults were eligible for inclusion. Data were pooled under a random effects model.

RESULTS: Two trials published as three manuscripts with a total of 207 patients were included. As per the Cochrane risk of bias tool, majority of parameter were labeled as high or unclear risk of bias. Bedaquiline compared with placebo was associated with a statistically significant decrease in time to conversion of positive sputum culture to negative at 8 and 24 weeks with a significant increase in mortality on long-term follow-up. There was no difference in completion rates between bedaquiline and placebo.

CONCLUSION: Bedaquiline is an effective treatment modality for MDR-TB but needs to be balanced against significant mortality. Future Phase 3 RCTs are needed to make a conclusive recommendation.

Allogeneic hematopoietic cell transplantation (allo-HCT) is the only known treatment that can offer a cure in mantle cell lymphoma, but it is unclear if regimen dose-intensity offers any advantage. We performed a systematic review/meta-analysis to assess efficacy of allo-HCT using myeloablative or reduced-intensity conditioning. We report results according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. On the basis of a relatively lower nonrelapse mortality and a slightly better progression-free survival/event-free survival and overall survival rates, reduced-intensity allo-HCT regimens appear to be the preferred choice when an allo-HCT is being considered for mantle cell lymphoma. The higher rate of relapse when offering reduced-intensity regimens cannot be ignored but certainly highlights opportunities to incorporate post-transplant strategies to mitigate this risk. A prospective comparative study is ultimately needed to generate more conclusive evidence.

INTRODUCTION: Management choices at the end of life are high-stake decisions fraught with emotions, chief among is regret. Our objective in this paper is to test the utility of a regret-based model to facilitate referral to hospice care while helping patients clarify their preferences on how they wish to spend the remaining days of their lives.

METHODS: A prospective cohort study that enrolled consecutive adult patients (n = 178) aware of the terminal nature of their disease. The patients were at the point in care where they had to decide between continuing potentially 'curative/life-prolonging' treatment (Rx) versus hospice care. Preferences were elicited using a Dual Visual Analog Scale regarding the level of regret of omission versus commission (RgO/RgC) towards hospice care and Rx. Each patient's RgO/RgC was contrasted against the predictive probability of death to suggest a management plan, which was then compared with the patient's actual choice. The probability of death was estimated using validated Palliative Performance Scale predictive model.

RESULTS: Eighty-five percent (151/178) of patients agreed with the model's recommendations (p < 0.000001). Model predicted the actual choices for 72% (128/178) of patients (p < 0.00001). Logistic regression analysis showed that people who were initially inclined to be referred to hospice and were predicted to choose hospice over disease-directed treatment by the regret model have close to 98% probability of choosing hospice care at the end of their lives. No other factors (age, gender, race, educational status and pain level) affected their choice.

CONCLUSIONS: Using regret to elicit choices in the end-of-life setting is both descriptively and prescriptively valid. People with terminal disease who are initially inclined to choose hospice and do not regret such a choice will select hospice care with high level of certainty.

BACKGROUND: The administrative process associated with clinical trial activation has been criticized as costly, complex, and time-consuming. Prior research has concentrated on identifying administrative barriers and proposing various solutions to reduce activation time, and consequently associated costs. Here, we expand on previous research by incorporating social network analysis and discrete-event simulation to support process improvement decision-making.

METHODS: We searched for all operational data associated with the administrative process of activating industry-sponsored clinical trials at the Office of Clinical Research of the University of South Florida in Tampa, Florida. We limited the search to those trials initiated and activated between July 2011 and June 2012. We described the process using value stream mapping, studied the interactions of the various process participants using social network analysis, and modeled potential process modifications using discrete-event simulation.

RESULTS: The administrative process comprised 5 sub-processes, 30 activities, 11 decision points, 5 loops, and 8 participants. The mean activation time was 76.6 days. Rate-limiting sub-processes were those of contract and budget development. Key participants during contract and budget development were the Office of Clinical Research, sponsors, and the principal investigator. Simulation results indicate that slight increments on the number of trials, arriving to the Office of Clinical Research, would increase activation time by 11 %. Also, incrementing the efficiency of contract and budget development would reduce the activation time by 28 %. Finally, better synchronization between contract and budget development would reduce time spent on batching documentation; however, no improvements would be attained in total activation time.

CONCLUSION: The presented process improvement analytic framework not only identifies administrative barriers, but also helps to devise and evaluate potential improvement scenarios. The strength of our framework lies in its system analysis approach that recognizes the stochastic duration of the activation process and the interdependence between process activities and entities.

INTRODUCTION: A Dieulafoy lesion (DL) of the small bowel can cause severe gastrointestinal bleeding, and presents a difficult clinical setting for endoscopists. Limited data exists on the therapeutic yield of treating DLs of the small bowel using single-balloon enteroscopy (SBE).

METHODS: Data were collected from Tampa General Hospital a 1 018-bed teaching hospital affiliated with University of South Florida in Tampa, Florida. Patients were selected from a database of patients that underwent SBE from January 2010 - August 2013.

RESULTS: Eight patients were found to have DL an incidence of 2.6 % of 309 SBE performed for obscure gastrointestinal bleeding. 7/8 were identified in the jejunum, with one found in the duodenum. The mean age of patients with DL was 71.5 years old. 6/8 patients were on some form of anticoagulant/antiplatelet agent. The primary modality of therapy employed was electrocautery, multipolar electrocoagulation in seven patients and APC (argon plasma coagulation) in one patient. In three patients, electrocoagulation was unsuccessful and hemostasis was achieved with clip placement. Three patients required repeat SBE with one found to have rebleeding from a failed clip with hemostasis achieved upon reapplication of one clip.

CONCLUSION: In our United States' experience, SBE offers a reasonable therapeutic approach to treat DL of the small bowel with low rates of rebleeding, no adverse events, and no patient requiring surgery.

BACKGROUND AND AIMS: Within the community, patients with positive capsule endoscopy (CE) are often referred to centers performing balloon-assisted enteroscopy. There is limited data evaluating the concordance and diagnostic/therapeutic yield of CE performed in the community versus CE conducted at institutions experienced with enteroscopy. The primary aim of this retrospective study was to evaluate the concordance between CE and SBE after CE was performed either in the community or at our tertiary care center.

METHODS: A total of 141 patients were analyzed after selecting patients undergoing evaluation of obscure GI bleeding from January 2010 to May 2014. Forty-seven CE were performed inside and the remaining 94 CE were performed at outside institutions prior to single-balloon enteroscopy at our institution. Agreement beyond chance was evaluated using kappa coefficient. A p value <5% was considered significant.

RESULTS: The most frequent findings on CE were vascular lesions in 39 patients (41.5%) within the referral group and 23 within inside patients (48.9%), followed by active bleeding/clots in 23 patients (24.5%) and in 14 patients (29.8%) respectively. There was a fair degree of concordance in the referral group for vascular lesions 0.23 (0.03-0.42) compared to a good degree in the inside group 0.65 (0.44-0.87). Fair agreement was found looking at ulcers within the referral group 0.29 (0.06-0.65) compared to a moderate agreement in the inside group 0.55 (0.17-0.94).

CONCLUSIONS: Degree of concordance for vascular lesions and ulcers was significantly higher for patients undergoing CE at our institution compared to those referred from the community. Patients referred to tertiary care centers for balloon-assisted enteroscopy may benefit from advanced endoscopists re-reading the capsule findings or even potentially repeating CE in hemodynamically stable patients if the study is not available.

BACKGROUND: Institutional Review Board (IRB) members have a duty to protect the integrity of the research process, but little is known about their basic knowledge of clinical research study designs.

METHODS: A nationwide sample of IRB members from major US research universities completed a web-based questionnaire consisting of 11 questions focusing on basic knowledge about clinical research study designs. It included questions about randomized controlled trials (RCTs) and other observational research study designs. Potential predictors (age, gender, educational attainment, type of IRB, current IRB membership, years of IRB service, clinical research experience, and self-identification as a scientist) of incorrect answers were evaluated using multivariate logistic regression models.

RESULTS: 148 individuals from 36 universities participated. The majority of participants, 68.9% (102/148), were holding a medical or doctoral degree. Overall, only 26.5% (39/148) of participants achieved a perfect score of 11. On the six-question subset addressing RCTs, 46.6% (69/148) had a perfect score. Most individual questions, and the summary model of overall quiz score (perfect vs. not perfect), revealed no significant predictors - indicating that knowledge deficits were not limited to specific subgroups of IRB members. For the RCT knowledge score there was one significant predictor: compared with MDs, IRB members without a doctoral degree were three times as likely to answer at least one RCT question incorrectly (Odds Ratio: 3.00, 95% CI 1.10-8.20). However, even among MD IRB members, 34.1% (14/41) did not achieve a perfect score on the six RCT questions.

CONCLUSIONS: This first nationwide study of IRB member knowledge about clinical research study designs found significant knowledge deficits. Knowledge deficits were not limited to laypersons or community advocate members of IRBs, as previously suggested. Akin to widespread ethical training requirements for clinical researchers, IRB members should undergo systematic training on clinical research designs.

BACKGROUND AND AIMS: Prior to the consensus guideline conference in 2007, eosinophilic esophagitis (EoE) was uncommon dominated by the fibrostenotic phenotype, but over the past decade has become a common cause of dysphagia with more inflammatory phenotypes diagnosed. We assessed the impact of guideline definitions on the characteristics of EoE phenotypes over the past 26 years at our institution.

METHODS: We reviewed the electronic health record of 75 consecutive patients meeting guideline definition EoE from 1/1988 to 5/2014. We separated groups based on 5-year intervals of diagnosis and phenotype. For continuous data, results were summarized as mean difference and standard deviation with 95 % confidence intervals.

RESULTS: Five groups based on 5-year intervals of diagnosis were identified: group 1-1988-1993 (n = 7), group 2-1994-1999 (n = 7), group 3-2000-2005 (n = 4), group 4-2006-2011 (n = 35), and group 5-2012-2014 (n = 22). Prior to 2000, all patients were diagnosed with fibrostenotic EoE. After the initial 2007 guideline conference, inflammatory EoE has predominated with only one-third diagnosed with fibrostenotic EoE. Prior to 2011, only two were diagnosed with PPI-REE. In the last 3 years, 8 out of 22 patients (32 %) had PPI-REE. Overall, 8 out of 10 (80 %) PPI-REE were the inflammatory phenotype. When comparing pre- (n = 18) and post (n = 57)-consensus definitions, there was a significant difference between age of diagnosis (30.710.2 vs. 41.3 ± 14.3; p = 0.001), age of symptom onset (18.4 +/15.2 vs. 32.4 ± 15.5), and initial esophageal diameter (10.5 ± 2.7 vs. 14.3 ± 4.2; p < 0.0001), respectively.

CONCLUSIONS: Fibrostenotic EoE has steadily decreased, and inflammatory EoE is now the most recognized form. Across our 26-year experience, there was a decrease in delay in diagnosis and severity of esophageal stricture. The pivotal change occurred around 2007 corresponding to the first EoE guideline emphasizing the impact and importance of early detection of disease.