Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.

BACKGROUND: Fibrotic interstitial lung diseases (fILDs) are a heterogeneous group of lung diseases associated with significant morbidity and mortality. Despite a large increase in the number of clinical trials in the last 10 years, current regulatory-approved management approaches are limited to two therapies that prevent the progression of fibrosis. The drug development pipeline is long and there is an urgent need to accelerate this process. This manuscript introduces the concept and design of an innovative research approach to drug development in fILD: a global Randomised Embedded Multifactorial Adaptive Platform in fILD (REMAP-ILD). METHODS: Description of the REMAP-ILD concept and design: the specific terminology, design characteristics (multifactorial, adaptive features, statistical approach), target population, interventions, outcomes, mission and values, and organisational structure. RESULTS: The target population will be adult patients with fILD, and the primary outcome will be a disease progression model incorporating forced vital capacity and mortality over 12 months. Responsive adaptive randomisation, prespecified thresholds for success and futility will be used to assess the effectiveness and safety of interventions. REMAP-ILD embraces the core values of diversity, equity, and inclusion for patients and researchers, and prioritises an open-science approach to data sharing and dissemination of results. CONCLUSION: By using an innovative and efficient adaptive multi-interventional trial platform design, we aim to accelerate and improve care for patients with fILD. Through worldwide collaboration, novel analytical methodology and pragmatic trial delivery, REMAP-ILD aims to overcome major limitations associated with conventional randomised controlled trial approaches to rapidly improve the care of people living with fILD.

High flow nasal catheter therapy versus non-invasive positive pressure ventilation in acute respiratory failure (RENOVATE trial): protocol and statistical analysis plan.

Background: The best way to offer non-invasive respiratory support across several aetiologies of acute respiratory failure (ARF) is presently unclear. Both high flow nasal catheter (HFNC) therapy and non-invasive positive pressure ventilation (NIPPV) may improve outcomes in critically ill patients by avoiding the need for invasive mechanical ventilation (IMV). Objective: Describe the details of the protocol and statistical analysis plan designed to test whether HFNC therapy is non-inferior or even superior to NIPPV in patients with ARF due to different aetiologies. Methods: RENOVATE is a multicentre adaptive randomised controlled trial that is recruiting patients from adult emergency departments, wards and intensive care units (ICUs). It takes advantage of an adaptive Bayesian framework to assess the effectiveness of HFNC therapy versus NIPPV in four subgroups of ARF (hypoxaemic non-immunocompromised, hypoxaemic immunocompromised, chronic obstructive pulmonary disease exacerbations, and acute cardiogenic pulmonary oedema). The study will report the posterior probabilities of non-inferiority, superiority or futility for the comparison between HFNC therapy and NIPPV. The study assumes neutral priors and the final sample size is not fixed. The final sample size will be determined by a priori determined stopping rules for non-inferiority, superiority and futility for each subgroup or by reaching the maximum of 2000 patients. Outcomes: The primary endpoint is endotracheal intubation or death within 7 days. Secondary outcomes are 28-day and 90-day mortality, and ICU-free and IMV-free days in the first 28 days. Results and conclusions: RENOVATE is designed to provide evidence on whether HFNC therapy improves, compared with NIPPV, important patient-centred outcomes in different aetiologies of ARF. Here, we describe the rationale, design and status of the trial. Trial registration:ClinicalTrials.gov NCT03643939.

Water Jet Erosion Performance of Carbon Fiber and Glass Fiber Reinforced Polymers.

Complex engineering challenges are revealed in the wind industry; one of them is erosion at the leading edge of wind turbine blades. Water jet erosive wear tests on carbon-fiber reinforced polymer (CFRP) and glass-fiber reinforced polymer (GFRP) were performed in order to determine their resistance at the conditions tested. Vacuum Infusion Process (VIP) was used to obtain the composite materials. Eight layers of bidirectional carbon fabric (0/90°) and nine glass layers of bidirectional glass cloth were used to manufacture the plates. A water injection platform was utilized. The liquid was projected with a pressure of 150 bar on the surface of the specimens through a nozzle. The samples were located at 65 mm from the nozzle at an impact angle of 75°, with an exposure time of 10, 20 and 30 min. SEM and optical microscopy were used to observe the damage on surfaces. A 3D optical profilometer helped to determine the roughness and see the scar profiles. The results showed that the volume loss for glass fiber and carbon fiber were 10 and 19 mm3, respectively. This means that the resistance to water jet erosion in uncoated glass fiber was approximately two times lower than uncoated carbon fiber.

Funding Research in Emergency Diagnostic Imaging: Summary of a Panel Discussion at the 2015 Academic Emergency Medicine Consensus Conference.

As part of the 2015 Academic Emergency Medicine consensus conference "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization," a panel of representatives from the National Institute of Health's Office of Emergency Care Research, the National Institute of Biomedical Imaging and Bioengineering, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute was assembled to discuss future opportunities for funding research in this particular area of interest. Representatives from these agencies and organizations discussed their missions and priorities and how they distribute funding. They also addressed questions on mechanisms for new and established researchers to secure future funding.

A statistical study of 1.000 cases oof leprosy observed in rangoon for approximately two years

The records of 1,000 cases of leprosy followed for an average of two years have been analyzed with the aid of punch cards. The type distribution of cases was 45 per cent tuberculoid, 23 per cent indeterminate, and 32 per cent lepromatous. The disease was most frequently noted by individuals of the 10-14 age group, although the group which came to the clinic in greatest numbers was 20-24. From data on the age of onset it appears that the percentage of leprosy was greater than the population percentage during the ages 10-39. The tuberculoid type occurred earlier than the others, and the history was shorter. In all types the percentages of cases with deformity increased with increase of age and duration of illness. The incidence of leprosy in Rangoon and environs was highest among Indians, next in Muslim-Burmese, less in Burmese and lest in Chinese; while the lepromatous rate was in the reverse order. The occurrence of ENL reactions was twice as frequent in the Burmese as in the Indian patients with lepromatous leprosy. Between the ages of 12 and 60, leprosy was much more common in males than in females, the disproportion being most marked in lepromatous cases. In the latter type, the frequency of deformities was also greater in males than females. Children had a higher proportion of tuberculoid and lower frequency of lepromatous cases, and a much lower deformity rate. Tuberculoid reactions were one-half as common, and ENL reactions one-fourth as common, in children as in adults. Under treatment the proportion of patients reaching an inactive stage was considerably higher among children than adults. Results of treatment with DDS were influenced by the age of the individuals and the duration of the disease. In tuberculoid cases with deformities or with reactions, the efficacy of treatment was lessened. In lepromatous cases the occurrence of ENL reaction interfered markedly with improvement in the clinical condition and bacteriologic status, as did irregularity of treatment. One-third of all cases reached an inactive stage, with faded lesions in tuberculoid and indeterminate cases, or negative smears for a year in those of the lepromatous type. The bacteriologic status of lepromatous cases improved in 87.2 per cent, remained stationary in 12.2 per cent, and deteriorated in only 0.6 per cent. Actually 17.5 per cent became negative. The chief factors involved in the occurrence of tuberculoid reactions were age, degree of infection, and positivity of...

Initial dosage of diaminodiphenyl sulfone in the treatment of tuberculoid leprosy

Two hundred cases of leprosy of the tuberculoid type were treated with DDS, one-half receiving gradually-increasing doses and the other half starting with the full dose at once. Some 122 of these cases (63 of the ascending-dose group and 59 of the maximal-dose group) were followed for an average of six months. The results were the same with regard to neuritis, reactions, side-effects of the drug, and beneficial effect of the treatment. Until a similar trial is carried out with lepromatous cases, however, it would not be wise to alter the conventional plan of therapy with DDS in cases of that form of the disease.

Cortisone in the treatment of reactional conditions in tuberculoid leprosy

Cortisone and DDS were used together in the treatment of reactions occurring in about a dozen cases of kleprosy of the tuberculoid type. Seven severe cases were followed and reported. Two of these were changed to potassium antimony tartrate injections, and one was given that drug for a recurrence of the condition. The other four patients did not require additional treatment for the reaction. In all but one case the edema and erythema could be controlled, but twelve weeks of treatment and an average total dose of four grams of cortisone were required. In addition to the improvement of the skin lesions, there was a slight reduction in the numbers of bacilli. None of the patients developed an exacerbation of neuritis while on DDS and cortisone. There were no untoward reactions, but the relatively high cost of the treatment requires emphasis.