Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 599.98K | Year: 2010
DESCRIPTION (provided by applicant): We discovered a new modality that will allow us to effectively remove excess fluid from patients and manage hypervolemia. Accordingly, we propose the development of a simple, safe miniature portable device that can slowly remove sufficient excess fluid, on a continuous basis, from patients with congestive heart failure (CHF). During this two-year Phase I study, we will design and develop this new fluid removal process, and define the design requirements for the miniaturized device, which will include a replaceable component. This replaceable component will be designed and evaluated in an in vitro testing circuit. Measurement of inflammatory mediators and clotting factors will be made, along with the continuous monitoring of blood flow rate, and associated pressures at several points in the circuit will be made. Given that there are no such portable devices available for clinical use, this device will have strong potential for improving survival and for decreasing costs for patients with recalcitrant congestive heart failure. Aside from the implied benefit of controlling congestive heart failure and potentially reducing left ventricular hypertrophy (LVH), a major cause of morbidity and mortality in dialysis patients, this device would be expected to dramatically reduce the excess, repetitive hospitalizations commonly incurred by dialysis patients who suffer from fluid overload and pulmonary edema. Reducing the number of these emergency hospitalizations would undoubtedly be a major cost savings for the Medicare-funded End Stage Renal Disease (ESRD) and CHF treatments. PUBLIC HEALTH RELEVANCE: This proposal addresses the development of a portable hemofiltration device which can be attached to a central venous catheter for the purpose of providing slow, continuous fluid removal for the maintenance of fluid balance in patients on chronic dialysis. This device would have the most value for those dialysis patients who are having difficulty in controlling blood pressure, fluid retention and pulmonary edema. The proposed design is appealing, with the utilization of a replaceable filtration unit which can be easily attached to a propulsion unit with miniature pumps for propelling blood through a hemofilter. This design could easily allow for slow, continuous fluid removal (1-3 ml/min) throughout the interdialytic period, allowing dialysis patients to avoid fluid overload. Aside from the implied benefit of controlling congestive heart failure and potentially reducing left ventricular hypertrophy (LVH), a major cause of morbidity and mortality in dialysis patients, this device would be expected to dramatically reduce the excess, repetitive hospitalizations commonly incurred by dialysis patients who suffer from fluid overload and pulmonary edema. Reducing the number of these emergency hospitalizations would undoubtedly be a major cost savings for the Medicare-funded End Stage Renal Disease (ESRD) program. This device could also be used for the management of congestive heart failure (CHF) in patients who are not on dialysis but in whom emergency admissions for pulmonary edema are a common occurrence.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.10M | Year: 2005
DESCRIPTION (provided by applicant): The clinical significance of chronic pro-inflammatory reactions in hemodialysis patients due to exposure to endotoxins has become a central issue in nephrology in recent years. The European Renal Association urges the routine use of ultrapure dialysate with bacteria and endotoxin levels < 0.1 cfu/ml and < 0.03 EU/ml, respectively. The American Association for the Advancement of Medical Instrumentation (AAMI) considered making similar recommendations for the United States, but chose not to do so at the time since many dialysis clinics would not be able to achieve this high level of dialysate purity without major changes in equipment and operating procedures. Recently, AAMI reduced its recommended levels of dialysate bacteria level from 2000 cfu/ml to 200 cfu/ml, and introduced an endotoxin limit of 2 EU/ml. The comparable European levels are 100 cfu/ml and 0.25 EU/ml for bacteria and endotoxins, respectively. To consistently achieve such high-purity levels in dialysate, two major challenges need to be overcome by dialysis clinics, namely: i) prevention of biofilm formation on surfaces of water systems in contact with liquids used to make the dialysate, and ii) ability to adhere to a standardized maintenance protocol to satisfy such low level of contamination. During the Phase I study, we developed a new technology based on the turbulent two-phase flow cleaning method that proved to remove more than 99% of mature biofilm from the distribution loops of a simulated dialysis center water system (DCWS), and with complete killing of any remaining surface bacteria. In the Phase II study, we propose to complete the development of the two-phase cleaning process and to develop an automated clean-inplace/ sanitize-in-place (CIP/SIP) system capable of delivering a validated cleaning/disinfecting cycle to all the components of the DCWS, including: RO distribution loop, bicarbonate distribution loop, connections to dialysis machines, RO-membrane unit and storage tanks. According to our plan, the distribution loops and connection tubing to dialysis machines will be cleaned and disinfected with the two-phase flow process, while storage tanks will be cleaned with a spray system, but without the need to fill such tanks. The entire cleaning/disinfection will be performed with the automated CIP/SIP system. The proposed system will perform a validated maintenance protocol with minimal labor requirements and in shorter times. The Specific Aims are: Aim 1 - To develop the cleaning procedure and analytical methodologies for each component of the DCWS using the simulated system developed in the Phase I study; Aim 2 - To develop an automated clean-in-place/sanitize-in-place (CIP/SIP) system, including: flow and chemical control, cycle steps and sequence, process indicators and parameters; Aim 3 - To validate the cleaning procedure for each dialysis water system component, including: distribution loops, connections to dialysis machines, storage tanks, and RO-membrane unit; Aim 4 - To verify the validated cleaning process and protocol in the clinical setting; and Aim 5 - To define water system designs and cleaning/disinfecting protocols necessary to consistently deliver high quality dialysate in the clinical setting.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 786.41K | Year: 2004
DESCRIPTION: (provided by the applicant) Frequent repair and replacement of dental handpieces (DHs) represent major dental practice costs necessitating an immediate technological solution. Dental handpiece (DH) failure is primarily caused by the combined
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase II | Award Amount: 1.24M | Year: 2009
DESCRIPTION (provided by applicant): Over one-quarter of all oral antibiotics prescribed in the United States are for acute otitis media. Tympanostomy tube (TT) insertion has become the treatment of choice for children with recurrent or chronic otitis media, with more than two million tubes sold annually in the US. Tympanostomy is the most common pediatric procedure under general anesthesia in the developed world. Chronic post-tympanostomy tube otorrhea (PTTO) is often refractory to treatment and inflicts significant morbidity in the form of hearing loss and long-term middle ear dysfunction. The Co-investigators have confirmed that chronic middle ear infection is a mucosal biofilm disease, and this may explain why otitis media is often difficult to treat with antibiotics. Biofilm growth on the TT surface and on middle ear mucosa may be a source of recurrent infections, and thus may also be a primary contributor. Between 10% and 50% of children with tubes experience otorrhea, and approximately 25% of children with a primary set of tubes will have to go on to have a second set of tubes. Based on prior studies, we believe that we can reduce the number of episodes and episode duration of PTTO by creating antimicrobial eluting ear tubes based on developing novel materials. We have designed a combination therapy that will provide broad-spectrum activity against planktonic and biofilm-forming species associated with otitis media. The antimicrobials selected will also reduce the likelihood of the development of resistant strains. We have demonstrated in Phase I that we can suppress biofilm formation and planktonic growth of Pseudomonas aeruginosa and Staphylococcus aureus for an extended period of time. By modifying the release kinetics, we believe we can increase this time period of efficacy even further. Our data also suggests that we have a synergistic interaction between antimicrobials. We have also demonstrated that we can make materials which are not cytotoxic to rabbit fibroblasts. The Specific Aims of this Phase II study are: 1) to optimize the release kinetics of our new materials and to injection mold TTs, 2) to confirm our in vitro studies with Haemophilus influenzae and Streptococcus pneumoniae, and quantify synergy and monitor for the development of resistant strains, 3) to assess ototoxicity, sensitivity and irritation in animal models, and 4) to compare the ability of experimental tubes with control tubes to treat and prevent PTTO in the chinchilla model of otitis media. PUBLIC HEALTH RELEVANCE: In Phase I, we developed a combination of antimicrobial/antibiotic compounds incorporated in host polymers that significantly inhibits bacterial attachment and biofilm development of organisms associated with otitis media. We plan to develop tympanostomy tube materials using such combination strategies and test their safety in an established animal model.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 2.30M | Year: 2011
DESCRIPTION (provided by applicant): The clinical significance of chronic pro-inflammatory reactions in dialysis patients due to exposure to endotoxin has become a central issue in nephrology. The European Renal Association urges the routine use of ultrapure dialysate with bacteria and endotoxin levels of lt 0.1 CFU/ml and lt 0.03 EU/ml, respectively. In the US, the maximum allowable limit of bacteria in water is 200 cfu/ml and the maximum allowable limit for endotoxin is 2 EU/ml. Considering the clinicalimplications and risks of exposing dialysis patients to a high level of cytokine- inducing molecules on a continuous basis, the US needs to quickly move to adopt the ultrapure dialysate (UPD) ISO 1163:2009 Standard. However, considering the state of US dialysis water systems, meeting such standard will be impossible to achieve without adopting new technologies that can eradicate biofilm from the dialysis water systems and correcting some inherent deficiencies in current maintenance protocols. In this FastTrack application, we propose to develop an integrated strategy to produce UPD based on using our CleanFlow device which delivers the highly effective two-phase flow (TPF) process. This strategy must consider treating all the surfaces of the water systemto the point where the dialysate enters the dialyzer. In this project we will develop methods and protocols to test the integrated strategy in dialysis clinics. We will verify that we can reduce inflammation markers (IL-6 and CRP) in patients treated withdialysate made according to this new strategy. The integrated strategy will include: 1) cleaning the distribution loops with the TPF process, 2) replacing the connection tubing to dialysis machines with a cleaned and disinfected set each time, and 3) ensuring that dialysis machines are equipped with a retentive ultrafilter before the dialyzer. We will compare the results of our integrated strategy with conventional methods, and will assess the impact of using or not using the ultrafilter on the results. Weplan to also include testing for bacterial DNA fragments in the dialysate before and after the ultrafilter. Development of this integrated strategy to produce UPD in US dialysis clinics is expected to decrease the chronic inflammation state in dialysis patients and increase responsiveness to erythropoietin. PUBLIC HEALTH RELEVANCE: In this Fast Track application, we propose to develop an integrated strategy to produce ultrapure dialysate (UPD) based on our proven capability of effectively removing biofilm from dialysis water systems using the CleanFlow device which delivers the novel two-phase flow (TPF) process. The strategy and approach detailed in this application address the logistical issues that clinics must adhere to in order to be able to make UPD, including: 1) the use of a retentive ultrafilter before the dialyzer, and 2) changing the connection tubing to dialysis machines during each cleaning. The project is directed to developing the technology and protocols that will enable US clinics tomeet the ISO 1163:2009 standard for UPD. Success of this development will make it possible for clinics with PVC piping construction to meet the above ISO standard at a reasonable cost, and will translate into decreasing the level of inflammatory biomarkers in dialysis patients and into increasing responsiveness to erythropoietin.