A System for Estimating Drug Delivery from a Dry Powder Inhaler by Analysis of Acoustic Recordings of Time-Stamped Inhaler Events

Inhaled medications are the mainstay of therapy in the treatment of chronic respiratory diseases like asthma and COPD because they allow delivery of the active ingredient directly to the site of action. Poor adherence to inhaled controller medications has been estimated to account for up to 60% of asthma-related hospitalizations and increased rates of 30- and 60- day hospital readmissions in patients with COPD. Numerous electronic monitoring devices have been developed over the last four decades to monitor temporal non-adherence; however, many of these devices do not monitor all or most aspects of inhaler technique. Currently used methods for monitoring inhaler technique, including subjective checklists, are suboptimal. There is a need to study the frequency of temporal and technique non-adherence in the Irish population and to investigate the impact of dosing and technique errors on drug delivery. Moreover, a comprehensive system of tracking the date and time of inhaler use, as well as the presence or absence of technique errors, on a daily basis is essential to not only an epidemiological understanding of inhaler use but to tailoring of inhaler training and clinical care plans to individual patients. This thesis describes the use of the INCATM device, a novel acoustic monitor, which provides longitudinal data on the date and time of inhaler use, as well as data on inhaler technique. Studies showed that inhalation flow rate, exhalation into the inhaler mouthpiece prior to inhalation, breath-hold duration and missed doses had a significant effect on delivered dose. Data on both temporal and technique adherence were combined in an algorithm, which provided a single measure of overall adherence, called “actual adherence”. The dose counter rate correlated poorly with INCATM derived adherence rates, highlighting the need to incorporate technologies, like the INCATM device, into clinical trials and patient care

A protocol for a randomised clinical trial of the effect of providing feedback on inhaler technique and adherence from an electronic device in patients with poorly controlled severe asthma

ntroduction In clinical practice, it is difficult to distinguish between patients with refractory asthma from those with poorly controlled asthma, where symptoms persist due to poor adherence, inadequate inhaler technique or comorbid diseases. We designed an audio recording device which, when attached to an inhaler, objectively identifies the time and technique of inhaler use, thereby assessing both aspects of adherence. This study will test the hypothesis that feedback on these two aspects of adherence when passed on to patients improves adherence and helps clinicians distinguish refractory from difficult-to-control asthma. Methods This is a single, blind, prospective, randomised, clinical trial performed at 5 research centres. Patients with partially controlled or uncontrolled severe asthma who have also had at least one severe asthma exacerbation in the prior year are eligible to participate. The effect of two types of nurse-delivered education interventions to promote adherence and inhaler technique will be assessed. The active group will receive feedback on their inhaler technique and adherence from the new device over a 3-month period. The control group will also receive training in inhaler technique and strategies to promote adherence, but no feedback from the device. The primary outcome is the difference in actual adherence, a measure that incorporates time and technique of inhaler use between groups at the end of the third month. Secondary outcomes include the number of patients who remain refractory despite good adherence, and differences in the components of adherence after the intervention. Data will be analysed on an intention-to-treat and a per-protocol basis. The sample size is 220 subjects (110 in each group), and loss to follow-up is estimated at 10% which will allow results to show a 10% difference (0.8 power) in adherence between group means with a type I error probability of 0.05. Trial registration number NCT01529697; Pre-results

Implementation of Gyro Accelerometer Sensor for Measuring Respiration Rate Based on Inhale and Exhale Using Kalman Filter

Respiratory rate is a fundamental vital sign that is sensitive to different pathological conditions including heart, lung, emotional stress, the influence of body temperature and activity fatigue. The respiratory rate in humans is measured by counting the number of breaths for one minute by monitoring and counting the number of times the chest rises and falls during the inhale and exhale process. Various methods for measuring respiratory rate that are commonly used including pneumograph, impedance and capnography are applied in patient monitoring. This study aims to examine and analyze the application of the kalman filter on the output of the gyro accelerometer sensor to increase the results of the detection of respiratory rates using the gyro accelerometer sensor. This study test was carried out using a patient simulator in Surabaya Ministry of Health Polytechnic nursing laboratory. This simulator patient can simulate respiration with a mechanical work system up and down the chest and abdomen, uses an Arduino Nano microcontroller to filter the output of the gyro accelerometer sensor and the results will be compared before and after the filter. The independent variable in this study is the respiration value, while the dependent variable is the sensor output before being filtered. In the relaxed condition of the respondent The most effective use of the kalman filter is found in the parameters R = 10, Q = 0.1 because in the use of these parameters, the value after being filtered has a value that tends to be stable. The highest error value in the application of the gyro accelerometer sensor occurs at sensor position 1 with R = 1 Q = 10 value of 2,6%. This study shows the effect of differences in respiration values before and after using a kalman filter. This study has limited differences in values that are far between the pre filter and after being filtered in several data collections

Current Insights on Lipid-Based Nanosystems

Lipid-based nanosystems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), cationic lipid nanoparticles, nanoemulsions, and liposomes, have been extensively studied to improve drug delivery through different administration routes. The main advantages of these systems are their ability to protect, transport, and control the release of lipophilic and hydrophilic molecules (either small-molecular-weight molecules or macromolecules); the use of generally recognized as safe (GRAS) excipients that minimize the toxicity of the formulations; and the possibility to modulate pharmacokinetics and enable the site-specific delivery of encapsulated payloads. In addition, the versatility of lipid-based nanosystems has further been demonstrated for the delivery of vaccines, the protection of active cosmetic ingredients, and the improvement of moisturizing properties of cosmetic formulations.Lipid-based nanosystems are well established and there are already different commercially approved formulations for various human disorders. This success has paved the way for the diversification of the pipeline of development, to address unmet medical needs for several indications, such as cancer, neurological disorders, and autoimmune, genetic, and infectious diseases.This Special Issue aims to update readers on the latest research on lipid-based nanosystems, both at the preclinical and clinical levels. A series of 15 articles (six reviews and nine studies) is presented, with authors from 12 different countries, showing the globality of the investigations that are being carried out in this area

Current Insights on Lipid-Based Nanosystems

Lipid-based nanosystems, including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), cationic lipid nanoparticles, nanoemulsions, and liposomes, have been extensively studied to improve drug delivery through different administration routes. The main advantages of these systems are their ability to protect, transport, and control the release of lipophilic and hydrophilic molecules (either small-molecular-weight molecules or macromolecules); the use of generally recognized as safe (GRAS) excipients that minimize the toxicity of the formulations; and the possibility to modulate pharmacokinetics and enable the site-specific delivery of encapsulated payloads. In addition, the versatility of lipid-based nanosystems has further been demonstrated for the delivery of vaccines, the protection of active cosmetic ingredients, and the improvement of moisturizing properties of cosmetic formulations.Lipid-based nanosystems are well established and there are already different commercially approved formulations for various human disorders. This success has paved the way for the diversification of the pipeline of development, to address unmet medical needs for several indications, such as cancer, neurological disorders, and autoimmune, genetic, and infectious diseases.This Special Issue aims to update readers on the latest research on lipid-based nanosystems, both at the preclinical and clinical levels. A series of 15 articles (six reviews and nine studies) is presented, with authors from 12 different countries, showing the globality of the investigations that are being carried out in this area

Understanding the flow behaviour in human maxillary sinuses for drug delivery applications

The sinus infection, chronic rhinosinusitis (CRS), has a prevalence ranging from 4.9% to 10.9% worldwide. When a nasal cavity (NC) is exposed to pathogens carried by inhaled aerosols, the attached sinuses, especially the maxillary sinus (MS), are highly prone to infection. The MS, a hollow organ attached to the NC, plays the role of thermal insulation in a human skull and affects the quality of the human voice. The only opening, which connects the NC to the MS, is a circular slit-like opening called the ostium, with a channel of <5 mm in diameter. The narrowness of the ostium is a significant challenge for drug delivery to the MS for the treatment of CRS. Various non-invasive devices, including nasal sprays and jet nebulizers, are available for drug delivery to the MS; however, due to the poor accessibility of the MS and the narrowness of the ostium, the efficiency of drug delivery to the MS is very low. Acoustic drug delivery (ADD) is a modern pathway for topical drug delivery to the MS, demonstrated to enhance drug delivery. This technology, using a fixed acoustic frequency, is currently available as a pre/post-surgical therapy but has not been able to demonstrate the full potential of delivering sufficient drug particles to the sinuses in most CRS cases. Several researchers investigated the effects of fixed acoustic frequencies, 45 Hz and 100 Hz, and reported an increase of 2 to 3-fold in the aerosol deposition in the MS when compared with conventional drug delivery. However, it has recently been hypothesised that the underlying mechanism of ADD is based on the Helmholtz resonator principle, where the air plug in the ostium oscillates when an external acoustic field is applied to the nostril. Oscillation of the air plug in the ostium leads to the delivery of the aerosols (nebulised drugs) from the NC to the MS. Accordingly, the maximum delivery of aerosols into the MS occurs when the amplitude of the oscillation of the air plug in the ostium is maximized. The maximum amplitude of the oscillation of the air plug in the ostium occurs at the resonance frequency of the NC-MS combination. In a limited number of the studies, the equation for a Helmholtz resonator (derived for a combination of a spherical cavity and a cylindrical neck), was used for predicting the resonance frequency of the NC-MS combination, which was superimposed onto the nebulised medication entering the nostril. Under this method, the efficiency of drug delivery to the MS increased 5-fold at most, when compared with non-acoustic drug delivery. In a more recent study, an acoustic frequency sweep was applied to the nostril, which showed a 10-fold increase in the aerosol deposition in the MS compared with conventional drug delivery. Such an increase in drug delivery efficiency is still insufficient for the treatment of CRS. Hence, it is important to predict the resonance frequency of the NC-MS combination accurately to increase the ADD efficiency significantly. The main aim of this thesis is to improve the efficiency of ADD to the MS by application of targeted excitation frequencies of the NC-MS combination to the nostril. Initially, the resonance frequency of an NC-MS combination was predicted as accurately as possible, and then the effect of various acoustic frequencies on ADD efficiency was investigated. In this thesis, several numerical models were explored, along with experimental testing. The numerical models include finite element analysis (FEA), computational fluid dynamics (CFD), and the Helmholtz resonator equation. The resonance frequencies of several simplified NC-MS combinations were predicted by this numerical model and compared with the experimental data to determine the most accurate numerical model. It was found that the Helmholtz resonator equation and FEA overpredict the resonance frequency of the NC-MS combination by 41% (depending on the size of the ostium and MS) compared with the experimental data. The CFD approach underpredicted the resonance frequency of the NC-MS combination by 8% compared with in-house experimental data, which proved to be the most accurate amongst the explored numerical models. The application of the Helmholtz resonator equation and FEA were shown not to provide an accurate prediction of the resonance frequency of the NC-MS combination because the equations of the Helmholtz resonator and the linearised Eulerian equation used in FEA do not account for the effect of the shape of the MS and the presence of the NC, while the Navier-Stokes equation used in CFD does. Using the CFD model, the effect of geometrical parameters such as the ostium length/diameter, MS shape/volume, and the NC width on the resonance frequency of an NC-MS combination were also studied. To examine the importance of the resonance frequency of the NC-MS combination on the ADD efficiency, a CFD model was developed to investigate the effect of various input frequencies, including the resonance and off-resonance frequencies, on the transport of particles from NC to the MS using an Eulerian-Lagrangian particle tracking scheme. Moreover, the effect of amplitude of the acoustic source and the inlet flow rate (at the nostril) on the transport of particles from the NC to the MS were investigated using a CFD model in a simplified NC-MS combination. The results showed that the highest transport of particles from the NC to the MS occurred when the inlet frequency was identical to the resonance frequency. It has been shown that the amplitude of the acoustic source has a monotonic relationship with the transport of particles from the NC to the MS; however, the airflow rate has an inverse relationship with it. Moreover, the effect of particle diameters and density on the penetration of particles in the MS were investigated using CFD modelling. It was found that increasing the particle diameter and density decreases the penetration of particles into the MS; the reason is that, in the presence of an acoustic field, increasing the particle diameter/density decreases the particle entrainment coefficient, which increases the acoustic Stokes number. An increase in the Stokes number reduces the ability of the particles to follow the oscillation of the air plug in the ostium with an amplitude identical to that of fluid. To explore the feasibility of ADD in practice, a 3D printed model of a realistic NC-MS combination was used to conduct the experiments to investigate the effect of resonance frequency on particle deposition in the MS, where a 2.5% sodium fluoride (NaF) was used to as the drug tracer. A loudspeaker was used to generate the acoustic field of interest, which was then applied to the nostril. The results show that when an acoustic field at a frequency equal to the resonance frequency of the NC-MS (obtained experimentally) is applied to the nostril, the particle deposition in the MS increases by 75-fold when compared with conventional drug delivery. The effect of input acoustic amplitude on particle deposition was also studied using a 3D printed model. The experimental data shows that increasing the input acoustic amplitude increases the particle deposition in the MS; however, increasing the amplitude above 120dB does not have a significant effect on the deposition. This might imply that at certain acoustic amplitudes a saturation point for aerosol deposition is reached. In the CFD simulation for a realistic NC-MS model, it was found that in the presence of an external acoustic field, not only does the air plug in the ostium oscillate but also a portion of the air plug in the middle meatus oscillates. Hence, to increase the ADD efficiency, it is important to transport particles to the middle meatus as much as possible. To do so, the effect of inlet flow parameters, as well as the impact of the diameter of the nozzle that injects the particles at the nostril, on the drug delivery to MM-Ostium regions was investigated. The term MM-Ostium refers to a region in the middle meatus (MM) where the ostium connects the MM to the MS. An increase in particle retention criterion in the MM-Ostium region was calculated to quantify the increase in the drug delivery to the MS region. The results have shown that the effect of turbulence at the inlet of the NC on drug delivery to the MM-Ostium region is negligible. It was also demonstrated that increasing the flow swirl at the inlet improves the total particle deposition due to the generation of centrifugal force, which acts on the particles in the nostril and vestibule. The results also suggest that drug delivery efficiency to the MS can be increased by using a swirling flow with a moderate swirl number of 0.6. Finally, it was found that decreasing the nozzle diameter can increase drug delivery to the MM-Ostium region, which subsequently increases the drug delivery to the MS.Thesis (Ph.D.) -- University of Adelaide, School of Mechanical Engineering, 202

XXIV congreso anual de la sociedad española de ingeniería biomédica (CASEIB2016)

En la presente edición, más de 150 trabajos de alto nivel científico van a ser presentados en 18 sesiones paralelas y 3 sesiones de póster, que se centrarán en áreas relevantes de la Ingeniería Biomédica. Entre las sesiones paralelas se pueden destacar la sesión plenaria Premio José María Ferrero Corral y la sesión de Competición de alumnos de Grado en Ingeniería Biomédica, con la participación de 16 alumnos de los Grados en Ingeniería Biomédica a nivel nacional. El programa científico se complementa con dos ponencias invitadas de científicos reconocidos internacionalmente, dos mesas redondas con una importante participación de sociedades científicas médicas y de profesionales de la industria de tecnología médica, y dos actos sociales que permitirán a los participantes acercarse a la historia y cultura valenciana. Por primera vez, en colaboración con FENIN, seJane Campos, R. (2017). XXIV congreso anual de la sociedad española de ingeniería biomédica (CASEIB2016). Editorial Universitat Politècnica de València. http://hdl.handle.net/10251/79277EDITORIA

Patient Safety and Quality: An Evidence-Based Handbook for Nurses

Compiles peer-reviewed research and literature reviews on issues regarding patient safety and quality of care, ranging from evidence-based practice, patient-centered care, and nurses' working conditions to critical opportunities and tools for improvement