Errors in Metered Dose Inhaler Use Amongst Pediatric Asthma Patients.

Purpose: The aim of this paper is to use easily accessible smartphones as a straightforward means for physicians to objectively check Medical Device Inhaler (MDI) technique, without the need for additional devices. Additionally, we seek to assess the frequency of inhaler technique errors and their impact on asthma control. Patients and Methods: Thirty-two children between the ages of 5 and 18 receiving asthma therapy through MDIs were included. Three surveys were administered to all participants to gauge device history, asthma control, and patient characteristics. Patient technique was scored using inhaler audio signals recorded with a smartphone. For subjects that were able, forced oscillation technique (FOT) was performed during tidal breathing conditions before and after corticosteroid administration. Results: 81% (25/31) of participants used their MDIs incorrectly with the most common errors being rapid shallow breathing, inadequate breath-holding, and excessive actuations. Poor inhaler technique correlated with poorly controlled asthma symptoms. Conclusion: The use of smartphone recordings can a convenient way to evaluate technique errors and could allow patients to demonstrate and refine their technique and usage without a doctor's visit, ensuring proper technique and enhancing treatment effectiveness.

Implantable intravascular defibrillator: evaluation of defibrillation waveforms with inferior vena cava electrode system.

BACKGROUND: A percutaneously placed, totally intravascular defibrillator has been developed that shocks via a right ventricular (RV) single-coil and titanium electrodes in the superior vena cava (SVC) and the inferior vena cava (IVC). This study evaluated the defibrillation threshold (DFT) with this electrode configuration to determine the effect of different biphasic waveform tilts and second-phase durations as well as the contribution of the IVC electrode. METHODS: Eight Bluetick hounds (wt = 30-40 kg) were anesthetized and the RV coil (first-phase anode) was placed in the RV apex. The intravascular defibrillator (PICD®, Model no. IIDM-G, InnerPulse Inc., Research Triangle Park, NC, USA) was positioned such that the titanium electrodes were in the SVC and IVC . Ventricular fibrillation was electrically induced and a Bayesian up-down technique was employed to determine DFT with two configurations: RV to SVC + IVC and RV to SVC. Three waveform tilts (65%, 50%, and 42%) and two second-phase durations (equal to the first phase [balanced] and truncated at 3 ms [unbalanced]) were randomly tested. The source capacitance of the defibrillator was 120 µF for all waveforms. RESULTS: DFT with the IVC electrode was significantly lower than without the IVC electrode for all waveforms tested (527 ± 9.3 V [standard error], 14.5 J vs 591 ± 7.4 V, 18.5 J, P < 0.001). Neither waveform tilt nor second-phase duration significantly changed the DFT. CONCLUSION: In canines, a totally intravascular implantable defibrillator with electrodes in the RV apex, SVC, and IVC had a DFT similar to that of standard nonthoracotomy lead systems. No significant effect was noted with changes in tilt or with balanced or unbalanced waveforms.

Effects of the Pratt pouch model of dispensing nevirapine prophylaxis on HIV exposed infant completion of 6 weeks of prophylaxis in Uganda.

INTRODUCTION: The innovative Pratt pouch could optimize dispensing nevirapine prophylaxis to HIV-exposed infants in pre-measured single dose pouches to increase completion of the full 6 week infant nevirapine regimen. MATERIALS AND METHODS: Nineteen health facilities with highest HIV positivity rates among pregnant women across 9 districts in southwest and central Uganda were assigned to control and intervention groups. HIV-positive women enrolled at intervention facilities received pouches filled with premeasured single doses of nevirapine using Uganda national guidelines, which were integrated into the existing drug distribution system. During antenatal care (ANC) women received 14 pouches to cover time until the 6 day postpartum visit, with an additional 8 pouches if women were delayed in returning to the facility, and 28 pouches after delivery. Women enrolled at control facilities received standard nevirapine syrup following delivery for postnatal infant prophylaxis. In a select number of intervention facilities, during ANC, women received all 42 pouches needed to complete the 6 weeks regimen. Medical record data from enrolled women were extracted; interviews with HIV-positive women during postnatal care visits were conducted. Data were collected January to August 2018 (control sites) and October 2019 to February 2020 (intervention sites). Unadjusted and adjusted logistic regression models were used to identify factors associated with facility delivery, postnatal care follow-up visit, and completion of the full 6 weeks infant nevirapine regimen. RESULTS: Significantly more women in the intervention (n = 320) versus control (n = 340) group had facility delivery (292/316, 92.4% versus 169/340, 49.7%, p<0.0001), postnatal visits within 2 weeks postpartum (295/297, 99.3% versus 133/340, 39.1%, p<0.0001) and reported their infants completing the full 6 weeks infant prophylaxis regimen (299/313, 95.5% versus 210/242, 86.8%, p = 0.0002). Dispensing 42 versus 14 pouches during ANC did not have negative effects on these outcomes. Among out-of-facility deliveries, a higher proportion of infants received nevirapine within 72 hours of birth in the intervention versus control group, 95.8% versus 77.9%. In multivariate models, the intervention group was the only significant factor associated with facility delivery or completion of the full 6 weeks infant prophylaxis. CONCLUSIONS: Use of the Pratt pouch resulted in an increase in HIV-exposed infants completing the full 6weeks prophylaxis regimen and associated benefits including increasing facility delivery and women's adherence to postnatal care services.

Effect of electrode surface area on thresholds for AC stimulation and ventricular fibrillation.

Unintended, weak AC stimulation (leakage currents) from medical devices can cause blood pressure collapse and ventricular fibrillation (VF), potentially even death. Yet, little is understood about AC cardiac stimulation. The objective of this paper is to establish the relationship between the stimulation and VF thresholds for electrode size and stimulation frequency. Twenty-four retired male breeder guinea pigs were anesthetized with isoflurane, a tracheotomy and thoracotomy were performed, and vitals were monitored using the lead II ECG and an optical plethysmograph. The circular flat ends of eleven stainless steel rods were used as electrodes with areas ranging from 0.1 to 26.79 mm2. In the first study, 60-Hz AC stimuli of 5 s duration were delivered with strengths from 25-3000 microA or until VF was induced. In the second group, the current thresholds at 20, 40, 80, and 160 Hz were determined at electrode areas of 0.2, 2.01, and 16.4 mm2. Reactions were categorized as having no effect, having some effect (EFFECT, typically blood pressure collapse), and inducing VF. On a log-log scale, electrode radii had a piecewise-linear relationship with the current thresholds for EFFECT (p < 0.005) and VF (p < 0.01). The liminal area determined by the piecewise-linear fit was 2.0 and 2.84 mm2 for EFFECT and VF, respectively. Above the liminal area, the threshold increased proportional to r(1.25) and r(0.95) (r = radius of electrode), for EFFECT and VF, respectively. Based on these experimental results, we present a theoretical framework to explain the electrode size-stimulation threshold variation for both low strength AC stimulation and VF initiation.

Technologies for clinically relevant physiological measurements in developing countries.

The 'Health for All by 2000' campaign included promotion of technologies that were known to be effective and inexpensive. The selected technologies were largely a failure. Among other problems, water pumps broke and could not be repaired in remote areas and latrines became disease concentration points when they were not properly maintained. These same problems plague more sophisticated healthcare technology. It is not sufficient for a technology to be known, effective and inexpensive for it to help the people of the developing world. There are additional obstacles. This article reviews the data, suggesting what additional obstacles exist to the successful implementation of healthcare technologies for the developing world with a particular emphasis on physiological measurements such as clinical laboratory and diagnostic medicine.

Very-long-chain acyl-coenzyme a dehydrogenase deficiency in mice.

Fatty acid oxidation (FAO) defects are inborn errors of metabolism clinically associated with cardiomyopathy and sudden infant death syndrome (SIDS). FAO disorders often present in infancy with myocardial dysfunction and arrhythmias after exposure to stresses such as fasting, exercise, or intercurrent viral illness. It is uncertain whether the heart, in the absence of stress, is normal. We generated very-long-chain acyl-coenzyme A dehydrogenase (VLCAD)-deficient mice by homologous recombination to define the onset and molecular mechanism of myocardial disease. We found that VLCAD-deficient hearts have microvesicular lipid accumulation, marked mitochondrial proliferation, and demonstrated facilitated induction of polymorphic ventricular tachycardia, without antecedent stress. The expression of acyl-CoA synthase (ACS1), adipophilin, activator protein 2, cytochrome c, and the peroxisome proliferator activated receptor gamma coactivator-1 were increased immediately after birth, preceding overt histological lipidosis, whereas ACS1 expression was markedly downregulated in the adult heart. We conclude that mice with VLCAD deficiency have altered expression of a variety of genes in the fatty acid metabolic pathway from birth, reflecting metabolic feedback circuits, with progression to ultrastructural and physiological correlates of the associated human disease in the absence of stress.

Experimental evidence of improved transthoracic defibrillation with electroporation-enhancing pulses.

There is considerable work on defibrillation wave form optimization. This paper determines the impedance changes during defibrillation, then uses that information to derive the optimum defibrillation wave form. METHODS PART I: Twelve guinea pigs and six swine were used to measure the current wave form for square voltage pulses of a strength which would defibrillate about 50% of the time. In guinea pigs, electrodes were placed thoracically, abdominally and subcutaneously using two electrode materials (zinc and steel) and two electrode pastes (Core-gel and metallic paste). RESULTS PART I: The measured current wave form indicated an exponentially increasing conductance over the first 3 ms, consistent with enhanced electroporation or another mechanism of time-dependent conductance. We fit this current with a parallel conductance composed of a time-independent component (g0 = 1.22 +/- 0.28 mS) and a time-dependent component described by g delta (1-e(-t/tau)), where g delta = 0.95 +/- 0.20 mS and tau = 0.82 +/- 0.17 ms in guinea pigs using zinc and Cor-gel. Different electrode placements and materials had no significant effect on this fit. From our fit, we determined the stimulating wave form that would theoretically charge the myocardial membrane to a given threshold using the least energy from the defibrillator. The solution was a very short, high voltage pulse followed immediately by a truncated ascending exponential tail. METHODS PART II: The optimized wave forms and similar nonoptimized wave forms were tested for efficacy in 25 additional guinea pigs and six additional swine using methods similar to Part I. RESULTS PART II: Optimized wave forms were significantly more efficacious than similar nonoptimized wave forms. In swine, a wave form with the short pulse was 41% effective while the same wave form without the short pulse was 8.3% effective (p < 0.03) despite there being only a small difference in energy (111 J versus 116 CONCLUSIONS: We conclude that a short pulse preceding a defibrillation pulse significantly improves efficacy, perhaps by enhancing electroporation.

Experimental verification of theoretical predictions concerning the optimum defibrillation waveform.

The efficacy of electrical therapy at terminating ventricular fibrillation is highly dependent on the waveform used. We present experimental results which test one theory for defibrillation waveform dependence. Forty-four defibrillation waveforms (22 monophasic, 22 biphasic) were designed according to the theoretical construct of Fishier (2000). The waveforms were then tested on 67 male guinea pigs (46 for monophasic, 21 for biphasic waveforms) using a custom designed defibrillator and 12-mm subcutaneous disc electrodes. There was considerable agreement between the theoretical and experimental results. For example, as predicted, the ascending exponential waveform of 1 ms proved to be the most effective (86.4%) monophasic waveform, where efficacy is the number of successful shocks divided by the total number delivered. In addition, the efficacy decrease with duration increase was accurately predicted by the model for monophasic waveforms. For biphasic waveforms, as predicted by the model, when the first phase was optimized, an increase in second phase duration caused an increase in defibrillation efficacy (10 of 11 tested duration pairs). We conclude that the theoretical framework adequately explains the mechanism by which the defibrillation waveform affects efficacy for monophasic waveforms and, in at least one aspect, biphasic waveforms.

The Pratt Pouch Provides a Three-Fold Access Increase to Antiretroviral Medication for Births outside Health Facilities in Southern Zambia.

INTRODUCTION: Modern day antiretroviral therapy allows HIV+ pregnant women to lower the likelihood of viral transmission to their infants before, during, and after birth from 20-45% to less than 5%. In developing countries, where non-facility births may outnumber facility births, infant access to safe antiretroviral medication during the critical first three days after birth is often limited. A single-dose, polyethylene pouch ("Pratt Pouch") addresses this challenge by allowing the medication to be distributed to mothers during antenatal care. METHODS: The Pratt Pouch was introduced as part of a one year clinical feasibility study in two districts in Southern Province, Zambia. Participating nurses, community health workers, and pharmacists were trained before implementation. Success in achieving improved antiretroviral medication access was assessed via pre intervention and post intervention survey responses by HIV+ mothers. RESULTS: Access to medication for HIV-exposed infants born outside of a health facility increased from 35% (17/51) before the introduction of the pouch to 94% (15/16) after (p<0.05). A non-significant increase in homebirth rates from 33% (pre intervention cohort) to 50% (post intervention cohort) was observed (p>0.05). Results remained below the national average homebirth rate of 52%. Users reported minimal spillage and a high level of satisfaction with the Pratt Pouch. CONCLUSION: The Pratt Pouch enhances access to infant antiretroviral medication in a rural, non-facility birth setting. Wide scale implementation could have a substantial global impact on HIV transmission rates from mother to child.

Providing Safe and Effective Preventative Antiretroviral Prophylaxis to HIV-exposed Newborns via a Novel Drug Delivery System in Tanzania.

BACKGROUND: In developing countries, antiretroviral therapy provides life-saving treatment to HIV-positive women and their children before, during and after birth. However, supply chain challenges such as long distances, medication shortages and nonfacility deliveries often compromise consistent access to prophylactic treatment for at-risk infants. A proposed intervention to address these challenges, often referred to as the "Pratt Pouch," allows for liquid-formulation medications, such as nevirapine (NVP), to be repackaged into single-dose pouches. These pouches are distributed antenatally. METHODS: HIV-positive women at Kilimanjaro Christian Medical Centre in Moshi, Tanzania received 14 pouches each containing a single dose of NVP for prevention of mother-to-child transmission. Women were trained on how to open the pouch and dispense the medication to their infants after delivery. All participating women were asked to return to Kilimanjaro Christian Medical Centre 7-14 days after delivery, where infant blood spots were collected to assess NVP levels. RESULTS: All enrolled women (21/21) administered NVP to their infants within 24 hours of birth. All enrolled infants (22/22) had NVP blood concentrations over 100 ng/mL and exhibited no health concerns attributable to over or under dosing. CONCLUSIONS: The Pratt Pouch intervention provides a clinically appropriate solution for addressing liquid-formulation antiretroviral access challenges in developing countries.

Advances in electrical and mechanical cardiac mapping.

Cardiac mapping--recording cardiac activity during electrophysiological testing--has evolved into an indispensable tool in studying the cardiac excitation process, analysing activation patterns, and identifying arrhythmogenic tissue. Cardiac mapping is a broad term that is used here to encompass applications that record electrical or mechanical activity of the heart or both. In recent years, simultaneous and sequential electrical mapping methods have been combined with direct mechanical measurements or imaging techniques to acquire information regarding both the electrical and mechanical activity of the heart (electromechanical mapping) during normal and irregular cardiac behavior. This paper reviews the emerging area of electromechanical mapping from the point of view of the applicable technology, including its history and application.

Design of an integrated sensor for in vivo simultaneous electrocontractile cardiac mapping.

While there is extensive mapping of the spread of electrical activity in the heart, there have been no measurements of electrical and localized mechanical, or contractile, activity. Yet the development of effective treatments for diseases like chronic heart failure and cardiac hypertrophy depend on the ability to quantify improvements in electrocontractile function. In this paper, we present a sensor that is capable of making simultaneous, electrocontractile measurements. Its small size facilitates placement in multiple myocardial sites for multichannel studies. Semiconductor strain gages are used for force sensing, and Ag/AgCl-plated tungsten electrodes act as electrogram sensors. The sensor contains electronics on-board, including instrumentation amplifiers and a microprocessor for data sampling and analog-to-digital conversion. Each sensor can accurately detect 0-245+/-5 mV in two electrogram channels with a sensitivity of 0.96+/-0.2 mV/step and less than 2% error, and 0-144+/-29 g of contractile force with a sensitivity of 0.56+/-0.11 g/step in the analog-to-digital conversion and less than 6% error. The sensor has been tested in vivo in open-chest rabbit and pig mapping studies. These studies indicated that the average peak-to-peak contractile force at the apex is smaller in the rabbit than the pig (13.3 versus 40.3 g), that the average peak-to-peak contractile force in the pig is smaller near the base than near the apex (31.3 versus 40.3 g), and that contractile force is visibly decreased during ventricular fibrillation compared to normal sinus rhythm.

A novel ultrasound technique to estimate right ventricular geometry during fibrillation.

Finite element modelling of the heart for the purpose of studying the electric fields of defibrillation shocks requires knowledge of the geometry of the heart during fibrillation. However, the standard method of measuring this geometry, MRI. cannot be used during fibrillation because the heart geometry changes rapidly and perhaps unpredictably. We present a new ultrasound approach to measuring the right ventricular geometry during fibrillation and preliminary data using this technique. In six anaesthetized pigs, we find that a short axis cross-sectional area of the right ventricle increases by 38% during a 30 s episode of ventricular fibrillation. A long axis cross-sectional area increases by 19% during this same time. By fitting parameters of a simple geometric model to the experimental data, we estimate that the volume of blood in the right ventricular cavity increases by approximately 30% during the episode of ventricular fibrillation. We present the first study of the RV area during-fibrillation with the estimated volume. Our data suggest changes in defibrillation threshold may be linked to current shunting through the increased blood volume.

Novel intravascular defibrillator: defibrillation thresholds of intravascular cardioverter-defibrillator compared to conventional implantable cardioverter-defibrillator in a canine model.

BACKGROUND: An intravascular, percutaneously placed implantable defibrillator (InnerPulse percutaneous intravascular cardioverter-defibrillator [PICD]) with a right ventricular (RV) single-coil lead and titanium electrodes in the superior vena cava (SVC) and the inferior vena cava (IVC) has been developed. OBJECTIVE: The purpose of this study was to compare defibrillation thresholds (DFTs) of the PICD to those of a conventional implantable cardioverter-defibrillator (ICD) in canines. METHODS: Eight Bluetick hounds were randomized to initial placement of either a PICD or a conventional ICD. For PICD DFTs, a single-coil RV defibrillator lead was placed in the RV apex, and the device was positioned in the venous vasculature with electrodes in the SVC and IVC. With the conventional ICD, an RV lead was placed in the RV apex and an SVC coil was appropriately positioned. The ICD active can (AC) was implanted in a subcutaneous pocket formed in the left anterior chest wall and connected to the lead system. DFT was determined by a three-reversal, step up-down method to estimate the 80% success level. Two configurations were tested for the conventional ICD (#1: RV to SVC+AC; #2: RV to AC). A single configuration (RV to SVC+IVC) was evaluated for the PICD. RESULTS: Mean PICD DFT was 14.8 ± 1.53 (SE) J. Conventional #1 configuration demonstrated mean DFT of 20.2 ± 2.45 J and #2 of 27.5 ± 1.95 J. The PICD had a significantly lower DFT than the better conventional ICD configuration (#1; mean difference 5.4 ± 2.1 J, P <.05, paired t-test, N = 8). CONCLUSION: The new intravascular defibrillator had a significantly lower DFT than the conventional ICD in this canine model.

Design of health care technologies for the developing world.

Approximately 20 years ago, the international community embarked on a project to bring health care to everyone by the year 2000 featuring, among other things, technologies that were known to be effective and economical. It was largely a failure. In fact, health care deteriorated in many of the target nations. Problems such as public mistrust, lack of spare parts, lack of required consumables, lack of reliable power and water, lack of public infrastructure such as roads, lack of technical expertise, and other problems plague health care technology in the developing world. Biomedical engineers are just beginning to quantify and address the barriers to technology unique to the developing world. This article reviews the barriers, both real and perceived, to the introduction of health care technology with a main focus on health care technology in hospitals.

Large sample test of defibrillation waveform sensitivity.

INTRODUCTION: An unknown mechanism causes defibrillation efficacy to be sensitive to the temporal pattern (waveform) of the delivered energy. Using a guinea pig model, we tested hypotheses in 140 defibrillation waveforms. METHODS AND RESULTS: Two hundred seven male guinea pigs (950 +/- 100 g) were instrumented to continuously monitor the ECG and an optical plethysmographic signal from a forepaw. Two amplifiers served as a voltage-based defibrillator with a maximum output of 400 V at 2 A. Defibrillation electrodes (12-mm diameter) were placed 40 mm apart on the thorax. Thirty ventricular fibrillation episodes were induced where the first 10 episodes were used to estimate ED50 for a biphasic pulse (7/2 msec) and the remaining episodes were defibrillated with 18 test waveforms and two control waveforms all at the ED50 energy. Seven groups of 20 waveforms were tested. We directly tested hypotheses based on charge banking/burping, frequency concentration, and stimulus strength/duration. Of the hypotheses tested, nine are able to predict at least a 10% change in efficacy (P < 0.05): parabolic fit to duration; maximum, minimum, and remaining delivered charge; power at peak frequency; stimulus charge; and maximum, minimum, and maximum of the absolute value of stimulus strength. However, of these, only three are independent predictors of waveform efficacy (P < 0.05, near-minimum residual variance): power at peak frequency; parabolic fit to the stimulus duration; and minimum stimulus strength. CONCLUSION: Stimulus strength and duration are the main determinants of the efficacy of a defibrillation waveform.