Adipose-Derived Regenerative Cell Transplantation for the Treatment of Hand Dysfunction in Systemic Sclerosis: A Randomized Clinical Trial.

Objective: Hand dysfunction is common in systemic sclerosis (SSc). We undertook this study to evaluate the capacity of autologous adipose-derived regenerative cells (ADRCs) to improve hand function in SSc patients.

Methods: The Scleroderma Treatment with Celution Processed Adipose Derived Regenerative Cells Trial was a prospective, randomized, double-blind trial of ADRCs, in which ADRCs were obtained from patients with SSc by small-volume adipose tissue harvest, and the fingers of each patient were injected with ADRCs.

Development of a novel digital breath-activated inhaler: Initial particle size characterization and clinical testing.

Background: Delivery of inhaled respiratory medications have been associated with variable delivery of drug due to errors in device operations and have not been designed to monitor true delivery of medication. A fully digital breath-activated inhaled (DBAI) delivery platform has been developed with integrated firmware and software to address these limitations.

Methods: the device was designed to produce similar aerosol particle output to a marketed albuterol MDI and to the albuterol/ipratropium combination in a soft mist inhaler (SMI).

Evaluation of pulsed electromagnetic field therapy for the treatment of chronic postoperative pain following lumbar surgery: a pilot, double-blind, randomized, sham-controlled clinical trial.

Background: The incidence of chronic postoperative pain following lumbar spinal surgery has increased with the overall increase in the prevalence of lumbar surgery. This study was conducted to evaluate the analgesic effectiveness of pulsed electromagnetic field (PEMF) therapy in subjects with persistent pain following lumbar surgery.

Patients And Methods: A randomized, double-blind, sham-controlled, multicenter study in 36 subjects with persistent low-back and/or radiating leg pain after lumbar surgery was conducted.

Fight, Flight, or Remain Silent? Juggling Multiple Accountabilities throughout the Formative Stage of a Neighborhood Revitalization Initiative.

This paper describes the experiences of a research team as they navigated uncertain ethical and political terrain throughout the formative stage of a public housing redevelopment project. Specifically, we discuss the challenges related to balancing multiple accountabilities and the tensions among the various roles and responsibilities that emanated from different accountabilities. Due to contractual obligations to our funding source, established relations with community partners, and an ethical imperative to align with those holding the least power, we grappled with embodying multiple and often conflicting roles.

Autologous Adipose Derived Regenerative Cells: A Platform for Therapeutic Applications.

Adipose derived regenerative cells (ADRCs) are a heterogeneous population of cells including multipotent adipose derived stems cells, other progenitor cells, fibroblasts, T-regulatory cells, and macrophages. Preclinical data exist supporting benefits that are predominantly through angiogenesis, modulation of inflammation, and wound remodeling. Such effects are likely paracrine in nature.

The Athena trials: Autologous adipose-derived regenerative cells for refractory chronic myocardial ischemia with left ventricular dysfunction.

Objective: To assess safety and feasibility of autologous adipose-derived regenerative cells (ADRCs), for treatment of chronic ischemic cardiomyopathy patients.

Background: Preclinical and early clinical trials suggest ADRCs have excellent potential for ischemic conditions.

Methods: The Athena program consisted of two parallel, prospective, randomized (2:1, active: placebo), double-blind trials assessing intramyocardial (IM) ADRC delivery [40-million, n = 28 (ATHENA) and 80-million (ATHENA II) cells, n = 3]).

Miami thrives: weaving a poverty reduction coalition.

In an environment where community based organizations are asked to do increasingly more to alleviate the effects of complex social problems, networks and coalitions are becoming the answer for increasing scale, efficiency, coordination, and most importantly, social impact. This paper highlights the formation of a poverty reduction coalition in south Florida. Our case study approach chronicles a developing coalition in Miami-Dade County and the role of one organization acting as lead to the initiative.

The localized inflammatory response to bronchoscopic thermal vapor ablation.

Background: Bronchoscopic thermal vapor ablation (BTVA) reduces lung volumes in emphysema patients by inducing a localized inflammatory response (LIR) leading to a healing process of fibrosis, but may also increase symptoms.

Objectives: We sought to evaluate whether the clinical manifestation of LIR correlated with patient outcome.

Methods: Respiratory adverse events and inflammatory markers were analyzed from a multicenter trial of BTVA in patients with upper-lobe-predominant emphysema.

Quality and reproducibility of spirometry in COPD patients in a randomized trial (UPLIFT®).

Background: This study explores spirometry quality and reproducibility in the Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT(®)) trial.

Methods: Four-year, randomized, double-blind, placebo-controlled, multicenter trial in 5993 patients with chronic obstructive pulmonary disease. Within-test variability of pre- and post-bronchodilator forced expiratory volume in 1 s (FEV(1)) was compared across study visits.

Treadmill endurance during 2-year treatment with tiotropium in patients with COPD: a randomized trial.

Background: Disease progression in COPD is associated with a decline in exercise performance over time. We assessed whether tiotropium might mitigate this by determining its effect on treadmill endurance time (ET) over 2 years.

Methods: This was a randomized, double-blind, placebo-controlled trial of tiotropium, 18 μg daily, in patients with COPD (FEV1/FVC < 70%; postbronchodilator FEV1 < 65%).

Evaluation of energy in heated water vapor for the application of lung volume reduction in patients with severe emphysema.

Background: A method of achieving endoscopic lung volume reduction for emphysema has been developed that utilizes precise amounts of thermal energy in the form of water vapor to ablate lung tissue.

Objective: This study evaluates the energy output and implications of the commercial InterVapor system and compares it to the clinical trial system.

Methods: Two methods of evaluating the energy output of the vapor systems were used, a direct energy measurement and a quantification of resultant thermal profile in a lung model.

Rationale for the development and the mechanism of action of endoscopic thermal vapor ablation (InterVapor) for the treatment of emphysema.

Background: Emphysema remains a disabling disease despite current treatment. Novel approaches to the underlying physiological abnormalities responsible for symptom generation are warranted.

Methods: A review of current hypotheses and preclinical and clinical data on the utility of endoscopic thermal vapor ablation (InterVapor) in the treatment of emphysema.

Exacerbation frequency and course of COPD.

Background: Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD). We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.

Methods: This retrospective analysis of data from the 4-year UPLIFT (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.

Characterization of outcomes 1 year after endoscopic thermal vapor ablation for patients with heterogeneous emphysema.

Introduction: Endoscopic lung volume reduction has been developed as a therapeutic option for advanced emphysema. Six-month results following treatment with endoscopic thermal vapor ablation (InterVapor; Uptake Medical, Tustin, CA) were described previously, and here we report observations from the 12-month assessment.

Methods: Two multicenter, international, single-arm trials of InterVapor (unilateral upper lobe treatment) in patients with upper lobe predominant emphysema were conducted.

Longitudinal inspiratory capacity changes in chronic obstructive pulmonary disease.

Background: The changes in inspiratory capacity (IC) over time in chronic obstructive pulmonary disease (COPD) patients are unknown. The Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial included IC measurements.

Methods: IC analysis from UPLIFT® (N = 5992) was performed at 1 and 6 months, and every 6 months through 4 years.

Effect of combination treatment on lung volumes and exercise endurance time in COPD.

Background: Data comparing two bronchodilators vs. one bronchodilator plus inhaled corticosteroid (ICS) on hyperinflation and exercise endurance in chronic obstructive pulmonary disease (COPD) are scarce, though these therapeutic strategies are widely used in clinical practice.

Methods: We performed a randomized, crossover clinical trial of two × 8 weeks comparing tiotropium (18 μg once daily) + salmeterol (50 μg twice daily) (T + S) to salmeterol + fluticasone (50/500 μg twice daily) (S + F) in COPD (forced expiratory volume in 1 s (FEV(1)) ≤65% predicted, and thoracic gas volume (TGV) ≥120% predicted).

Thermal effect of endoscopic thermal vapour ablation on the lung surface in human ex vivo tissue.

Purpose: An investigation of the thermal effect and the potential for injury at the lung surface following thermal vapour ablation (InterVapor), an energy-based method of achieving endoscopic lung volume reduction.

Methods: Heated water vapour was delivered to fifteen ex vivo human lungs using standard clinical procedure, and the thermal effect at the visceral pleura was monitored with an infrared camera. The time-temperature response was analysed mathematically to determine a cumulative injury quotient, which was compared to published thresholds.

Comparison of human lung tissue mass measurements from ex vivo lungs and high resolution CT software analysis.

Background: Quantification of lung tissue via analysis of computed tomography (CT) scans is increasingly common for monitoring disease progression and for planning of therapeutic interventions. The current study evaluates the quantification of human lung tissue mass by software analysis of a CT to physical tissue mass measurements.

Methods: Twenty-two ex vivo lungs were scanned by CT and analyzed by commercially available software.

Efficacy of tiotropium in COPD patients with FEV1 ≥ 60% participating in the UPLIFT® trial.

GOLD stage II COPD encompasses patients with FEV₁ 50-80% predicted. A published trials review suggested that benefits of maintenance therapy are limited to patients with FEV₁ <60% predicted. We previously reported data demonstrating the efficacy of tiotropium in GOLD stage II disease in the 4-year UPLIFT® trial, and present here a further analysis of a sub-category of GOLD stage II patients with post-bronchodilator FEV1 ≥60% predicted from UPLIFT®.

Efficacy of bronchoscopic thermal vapor ablation and lobar fissure completeness in patients with heterogeneous emphysema.

Background: Bronchoscopic thermal vapor ablation (BTVA) ablates emphysematous tissue through a localized inflammatory response followed by contractive fibrosis and tissue shrinkage leading to lung volume reduction that should not be influenced by collateral ventilation.

Objectives: To determine the correlation of clinical data from a trial of BTVA with fissure integrity visually assessed by computed tomography (CT).

Methods: We conducted a single-arm study of patients with upper lobe-predominant emphysema (n = 44).

Cause-specific mortality adjudication in the UPLIFT® COPD trial: findings and recommendations.

Mortality is an important endpoint in chronic obstructive pulmonary disease (COPD) trials, although accurately determining cause of death is difficult. In the Understanding the Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial, a mortality adjudication committee (MAC) provided systematic, independent and blinded assessment of cause-specific mortality of all 981 reported deaths. Here we describe this process of mortality adjudication and methodological revisions introduced to help standardise the adjudication of two areas recognised to pose particular difficulty; firstly, the classification of fatal COPD exacerbations that occur in the setting of pneumonia and secondly, the categorisation of sudden death.

Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema.

The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA.

Adverse health consequences in COPD patients with rapid decline in FEV1--evidence from the UPLIFT trial.

Background: The rate of decline in forced expiratory volume in 1 second (FEV1) is representative of the natural history of COPD. Sparse information exists regarding the associations between the magnitude of annualised loss of FEV1 with other endpoints.

Methods: Retrospective analysis of UPLIFT® trial (four-year, randomized, double-blind, placebo-controlled trial of tiotropium 18 μg daily in chronic obstructive pulmonary disease [COPD], n = 5993).

Tiotropium reduces risk of exacerbations irrespective of previous use of inhaled anticholinergics in placebo-controlled clinical trials.

Background: Data have highlighted the potential bias introduced by withdrawal of inhaled corticosteroids at randomization in chronic obstructive pulmonary disease trials examining inhaled corticosteroids. Analyses were conducted to determine whether this was true of inhaled anticholinergic withdrawal in tiotropium trials.

Methods: A pooled analysis of randomized, double-blind, placebo-controlled, parallel-group tiotropium trials of at least six months' duration was performed.

Risk of nonlower respiratory serious adverse events following COPD exacerbations in the 4-year UPLIFT® trial.

Introduction: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with systemic consequences. Data from a 4-year trial (Understanding Potential Long-term Impacts on Function with Tiotropium [UPLIFT(®)], n = 5,992) were used to determine risk for nonlower respiratory serious adverse events (NRSAEs) following an exacerbation.

Methods: Patients with ≥ 1 exacerbation were analyzed.