Drug-dosage indicator
Simple indicator, easily incorporated into drug container, allows patient to keep track of medication intake. Device can be used with loose tablets or liquids.
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Simple indicator, easily incorporated into drug container, allows patient to keep track of medication intake. Device can be used with loose tablets or liquids.
The radiation hazard inside spacecraft is discussed with emphasis on its effects on the crew, biological specimens, and spacecraft instruments. The problem of light flash sensations in the eyes of astronauts is addressed and experiment MA-106 is described. In this experiment, light flashes seen by blindfolded astronauts were counted and high energy cosmic ray intensity in the command module cabin were measured. The damage caused by cosmic ray hits on small living organisms was investigated in the Biostack 3 experiment (MA-107). Individual cosmic rays were tracked through layers of bacterial spores, small seeds, and eggs interleaved with layers of AgCl-crystal wafers, special plastic, and special photographic film that registered each cosmic ray particle passed.
The objective of this investigation was to examine the relationship between irradiation level (proton dose), microstructure, and stress levels in chemical vapor deposited diamond and polysilicon film using crosssectioned specimens. However, the emphasis was placed on the diamond specimen because diamond holds much promise for use in advanced technologies. The use of protons allows not only the study of the charged particle that may cause the most microstructural damage in Earth-orbit microelectromechanical systems (MEMS) devices, but also allows the study of relatively deeply buried damage inside the diamond material. Using protons allows these studies without having to resort to megaelectronvolt implant energies that may create extensive damage due to the high energy that is needed for the implantation process. Since 1 MEMS devices operating in space will not have an opportunity to reverse radiation damage via annealing, only nonannealed specimens were investigated. The following three high spatial resolution techniques were used to examine these relationships: (I) Scanning electron microscopy, (2) micro-Raman spectroscopy, and (3) micro x-ray diffraction.
Radiation-transport codes or radiation-analysis tools are used in the spacecraft-design community to define and assess the local radiation levels. Among various radiation-transport/analysis tools available, SHIELDOSE-2 is commonly used in the early spacecraft-design phases because it has been established that it provides reasonably reliable results with relatively rapid computation time. The NASA Engineering and Safety Center initiated a two-phased study: (1) to better understand and document the SHIELDOSE-2 code capabilities and limitations, and (2) to recommend alternative tools to use for cases where SHIELDOSE-2 is not applicable. This report provides a summary of the Phase 1 study.
Radiation-transport codes or radiation-analysis tools are used in the spacecraft-design community to define and assess the local radiation levels. Among various radiation-transport/analysis tools available, SHIELDOSE-2 is commonly used in the early spacecraft-design phases because it has been established that it provides reasonably reliable results with relatively rapid computation time. The NASA Engineering and Safety Center initiated a two-phased study: (1) to better understand and document the SHIELDOSE-2 code capabilities and limitations, and (2) to identify alternative tools to use for cases where SHIELDOSE-2 is not applicable. This report provides a summary of the Phase 2 study.
Intramuscular (IM) injections of promethazine in 25 mg or 50 mg dosages are commonly used to treat space motion sickness in astronauts. The present study examined the effects of IM injections of promethazine on neuropsy-chological performance, mood states, and motion sickness tolerance in humans. Twelve men, mean age 36 plus or minus 3.1 participated in one training (no injections) and three treatment conditions: a 25 mg injection of promethazine, a 50 mg injection of promethazine, and a placebo injection of sterile saline. Each condition, spaced at 7 day intervals, required an 8-10 hr session in which subjects were given four repetitions of 12 performance tasks, and one rotating chair motion sickness test. On the training day subjects were trained on each task to establish stability and proficiency. On treatment days, the order in which the drug or placebo was assigned to subjects was counter-balanced and a double-blind technique was used. Statistically significant decrements in performance were observed on 10 of 12 tasks when subjects were given 25 mg or 50 mg of promethazine as compared to the placebo. Performance decrements were associated with mean blood alcohol dose equivalency levels of 0.085% for 25 mg and 0. 1 37% for 50 mg dosages. The mood scale results showed significant changes in individual subjective experiences with maximum deterioration in the arousal state and fatigue level. When compared to placebo significant increases in motion sickness tolerance were found for both dosages of promethazine. These data suggest that effective dosages of promethazine currently used to counteract motion sickness in astronauts may significantly impair task components of their operational performance.
An implantable programmable infusion pump (IPIP) is disclosed and generally includes: a fluid reservoir filled with selected medication; a pump for causing a precise volumetric dosage of medication to be withdrawn from the reservoir and delivered to the appropriate site within the body; and, a control means for actuating the pump in a safe and programmable manner. The control means includes a microprocessor, a permanent memory containing a series of fixed software instructions, and a memory for storing prescription schedules, dosage limits and other data. The microprocessor actuates the pump in accordance with programmable prescription parameters and dosage limits stored in the memory. A communication link allows the control means to be remotely programmed. The control means incorporates a running integral dosage limit and other safety features which prevent an inadvertent or intentional medication overdose. The control means also monitors the pump and fluid handling system and provides an alert if any improper or potentially unsafe operation is detected.
A significant operational problem impacting upon the Space Shuttle program involves the astronaut's ability to safely egress from the Orbiter during an emergency situation. Following space flight, astronauts display significant movement problems. One variable which may contribute to increased movement ataxia is deuterium (D2O). Deuterium is present in low levels within the Orbiter's water supply but may accumulate to significant physiological levels during lengthy missions. Deuterium was linked to a number of negative physiological responses, including motion sickness, decreased metabolism, and slowing of neural conduction velocity. The effects of D2O on static postural control in response to a range of dosage levels were investigated. Nine sugjects were divided into three groups of three subjects each. The groups were divided into a low, medium, and a high D2O dosage group. The subjects static posture was assessed with the use of the EquiTest systems, a commercially available postural control evaluation system featuring movable force plates and a visual surround that can be servoed to the subject's sway. In addition to the force plate information, data about the degree of subject sway about the hips and shoulders was obtained. Additionally, surface electromyographic (EMG) data from the selected lower limb muscles were collected along with saliva samples used to determine the amount of deuterium enrichment following D2O ingestion. Two baseline testing sessions were performed using the EquiTest testing protocol prior to ingestion of the D2O. Thirty minutes after dosing, subjects again performed the tests. Two more post-dosing tests were run with an interest interval of one hour. Preliminary data anlaysis indicates that only subjects in the igh dose group displayed any significant static postural problems. Future analyses of the sway and EMG is expected to reveal significant variations in the subject's postural control strategy following D2O dosing. While functionally significant static postural problems were not commonly observed, subjects in both the medium and high dosage groups displayed significant, and in some cases, severe voluntary movement problems.
Heretofore, a number of papers reported the detection of high Be-7 concentration in the LDEF. It sounded alarming for space flight in the LDEF orbit, since Be-7 has a half life of 54 days and emits gamma rays of 0.48 MeV which is ionizing radiation. Two concerns are raised: the high concentration of harmful rays to spacecraft crews; and the concentration damage to spacecraft electronic components. A need was established to estimate the dosage of this concentration and compare the value of the allowed limits. As a result, the dosage was calculated of 0.03 rad. When this is compared with the human limit of 25 rads and the susceptibility requirement of 800 rads, the Be-7 amount should not be considered critical. The calculation of Be-7 dosage is detailed.
Several scientific, regulatory, and policy-coordinating bodies have developed methods for predicting community response to sonic booms. The best known of these is the dosage-response relationship of Working Group 84 of the National Academy of Science's Committee on Hearing, Bioacoustics and Biomechanics. This dosage-response relationship between C-weighted DayNight Average Sound Level and the prevalence of annoyance with high energy impulsive sounds was derived from limited amounts of information about community response to regular, prolonged, and expected exposure to artillery and sonic booms. U.S. Army Regulation 201 adapts this approach to predictions of the acceptability of impulsive noise exposure in communities. This regulation infers equivalent degrees of effect with respect to a well known dosage-response relationship for general (nonimpulsive) transportation noise. Differences in prevalence of annoyance predicted by various relationships lead to different predictions of the compatibility of land uses with sonic boom exposure. An examination of these differences makes apparent several unresolved issues in current practice for predicting and interpreting the prevalence of annoyance due to sonic boom exposure.
The bone effects of oral dosages of calcium chloride with or without supplementary sodium fluoride were assessed in antiorthostatically suspended mice. Two calcium dosages were used to replace half (3.1 mM) or all(6.3 mM) of the dietary calcium lost due to reduced food intake by the suspended mice. Two groups of 6.3 mM CaCl2-treated mice were additionally treated with 0.25 or 2.5 mM NaF. The results indicate that supplementation of the mouse drinking water with calcium salts prevents bone changes induced by short-term suspension, while calcium salts in combination with fluoride are less effective as fluoride dosage increases. However, the calcium supplements change the relationship between the femur mechanical properties and the mineral composition of the bone. Because of this, it appears that oral calcium supplements are effective through a mechanism other than simple dietary supplementation and may indicate a dependence of bone consistency on systemic and local fluid conditions.
Oxidative damages by ionizing radiation are the source of radiation-induced carcinogenesis, damage to the central nervous system, lowering of the immune response, as well as other radiation-induced damages to human health. Monte Carlo track simulations and kinetic modeling of radiation damages to the DNA employ available molecular and cellular data to simulate the biological effect of high and low LET radiation io the DNA. While the simulations predict single and double strand breaks and base damages, so far all complex lesions are the result of stochastic coincidence from independent processes. Tandem double lesions have not yet been taken into account. Unlike the standard double lesions that are produced by two separate attacks by charged particles or radicals, tandem double lesions are produced by one single attack. The standard double lesions dominate at the high dosage regime. On the other hand, tandem double lesions do not depend on stochastic coincidences and become important at the low dosage regime of particular interest to NASA. Tandem double lesions by hydroxyl radical attack of guanine in isolated DNA have been reported at a dosage of radiation as low as 10 Gy. The formation of two tandem base lesions was found to be linear with the applied doses, a characteristic of tandem lesions. However, tandem double lesions from attack by a charged particle have not been reported.
Space Motion sickness (SMS) is an age old problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is the most frequently used drug for the treatment of motion sickness (MS) which is currently available in transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability thus allowing precise and reduced dosing options in addition to offering rescue and treatment options. As such, an intranasal gel dosage formulation of scopolamine (INSCOP) was developed and Pharmacokinetics (PK) and bioavailability were determined under IND guidelines. The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostatic bedrest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 and 0.4 mg doses of INSCOP during AMB and ABR in a four-way crossover design. Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose. Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration versus time curve (AUC) during ABR after the 0.4 mg dose. This difference in AUC and Cls at the higher but not the lower dose during ABR may suggest that ABR may affect metabolism and/or clearance at higher doses of INSCOP. These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.
Statement of Purpose, Innovation or Hypothesis: Space Motion sickness (SMS) is a long-standing problem for astronauts on both short and long duration space flights. Scopolamine (SCOP) is frequently used for the treatment of motion sickness (MS), and is available as transdermal patch and tablet dosage forms. These formulations of SCOP are ineffective for the treatment of SMS. Intranasal dosage forms are noninvasive with rapid absorption and enhanced bioavailability, thus allowing precise and reduced dosing in addition to offering rescue and treatment options. An intranasal gel dosage formulation of scopolamine (INSCOP) was developed and pharmacokinetics (PK) and bioavailability were determined in clinical trials with human subjects under IND guidelines.Description of Methods and Materials: The present clinical trial compares PK and bioavailability of INSCOP in 12 normal, healthy subjects (6 male/ 6 female) during ambulation (AMB) and antiorthostaticbed rest (ABR) used as a ground-based microgravity analog. Subjects received 0.2 mg and 0.4 mg doses of INSCOP during AMB and ABR in a 4-way crossover design.Data and Results: Results indicated no difference between AMB and ABR in PK parameters after 0.2 mg dose, Clearance (Cls) decreased with a concomitant increase in maximum concentration and area under concentration-versus-time curve (AUC) during ABR after the 0.4 mg dose.Interpretation, Conclusion or Significance: The difference in AUC and Cls at the higher (0.4 mg) but not the lower dose (0.2 mg) during ABR suggests that ABR may affect metabolism and/or clearance of INSCOP at higher doses . These results indicate that dosing adjustment may be required for treatment of SMS with INSCOP in space.
Motion sickness (MS) has been a problem associated with space flight, the modern military and commercial air and water transportation for many years. Clinical studies have shown that scopolamine is the most effective medication for the prevention of motion sickness (Dornhoffer et al, 2004); however, the two most common methods of administration (transdermal and oral) have performance limitations that compromise its utility. Intranasal administration offers a noninvasive treatment modality, and has been shown to counter many of the problems associated with oral and transdermal administration. With the elimination of the first pass effect by the liver, intranasal delivery achieves higher and more reliable bioavailability than an equivalent oral dose. This allows for the potential of enhanced efficacy at a reduced dose, thus minimizing the occurrence of untoward side effects. An Intranasal scopolamine (INSCOP) gel formulation was prepared and tested in four ground-based clinical trials under an active Investigational New Drug (IND) application with the Food and Drug Administration (FDA). Although there were early indicators that the intranasal gel formulation was effective, there were aspects of formulation viscosity and the delivery system that were less desirable. The INSCOP gel formulation has since been reformulated into an aqueous spray dosage form packaged in a precise, metered dose delivery system; thereby enhancing dose uniformity, increased user satisfaction and palatability, and a potentially more rapid onset of action. Recent reports of new therapeutic indications for scopolamine has prompted a wide spread interest in new scopolamine dosage forms. The novel dosage form and delivery system of INSCOP spray shows promise as an effective treatment for motion sickness targeted at the armed forces, spaceflight, and commercial sea, air, and space travel markets, as well as prospective psychotherapy for mental and emotional disorders.
A strategic focus area for NASA is to pursue the development of technologies which support exploration in space beyond the current inhabited region of low earth orbit. An unresolved issue for crewed deep space exploration involves limiting crew radiation exposure to below acceptable levels, considering both solar particle events and galactic cosmic ray contributions to dosage. Galactic cosmic ray mitigation is not addressed in this paper, but by addressing credible, easily implemented, and mass efficient solutions for the possibility of solar particle events, additional margin is provided that can be used for cosmic ray dose accumulation. As a result, NASA s Advanced Engineering Systems project office initiated this Radiation Storm Shelter design activity. This paper reports on the first year results of an expected 3 year Storm Shelter study effort which will mature concepts and operational scenarios that protect exploration astronauts from solar particle radiation events. Large trade space definition, candidate concept ranking, and a planned demonstration comprised the majority of FY12 activities. A system key performance parameter is minimization of the required increase in mass needed to provide a safe environment. Total system mass along with operational assessments and other defined protection system metrics provide the guiding metrics to proceed with concept developments. After a downselect to four primary methods, the concepts were analyzed for dosage severity and the amount of shielding mass necessary to bring dosage to acceptable values. Besides analytical assessments, subscale models of several concepts and one full scale concept demonstrator were created. FY12 work terminated with a plan to demonstrate test articles of two selected approaches. The process of arriving at these selections and their current envisioned implementation are presented in this paper.
PURPOSE: Exploration space missions pose several challenges to providing a comprehensive medication formulary designed to accommodate the size and space limitations of the spacecraft; while addressing the individual medications needs and preferences of the Crew; the negative outcome of a degrading inventory over time, the inability to resupply before expiration dates; and the need to properly forecast the best possible medication candidates to treat conditions that will occur in the future. METHODS: The Pharmacotherapeutics Discipline has partnered with the Exploration Medical Capabilities (ExMC) Element to develop and propose a research pathway that is comprehensively focused on evidence-based models and theories, as well as on new diagnostic tools and treatments or preventive measures aimed at closure of the Med02 “Pharmacy” Gap; defined in the Human Research Program’s (HRP) risk-based research strategy. The Med02 Gap promotes the challenge to identify a strategy to ensure that medications used to treat medical conditions during exploration space missions are available, safe, and effective. It is abundantly clear that pharmaceutical intervention is an essential component of risk management planning for astronaut healthcare during exploration space. However, the quandary still remains of how to assemble a formulary that is comprehensive enough to prevent or treat anticipated medical events; and is also chemically stable, safe, and robust enough to have sufficient potency to last for the duration of an exploration space mission. In cases where that is not possible, addressing this Gap requires exploration of novel drug development techniques, dosage forms, and dosage delivery platforms that enhance chemical stability as well as therapeutic effectiveness. RESULTS: The proposed research pathway outlines the steps, processes, procedures, and a research portfolio aimed at identifying a capability that will provide a safe and effective pharmacy for any specific exploration Design Reference Mission (DRM). The proposed approach to building this research portfolio is to seek research projects that concentrate on four major focus areas; (1) Formulary selection, (2) Formulary potency and shelf life, (3) Formulary safety and toxicity, and (4) Novel technology and innovation such as portable real-time chemical analysis innovative drug therapies and dosage and delivery platforms. CONCLUSION: The research pathway has been completed and presented to the HRP. In spring 2017, it is scheduled to be reviewed by a panel of pharmaceutical and clinical experts that will evaluate the scientific merit and operational feasibility of the research pathway, as well as make suggestions for any warranted additions or improvements. Once finalized, the ExMC Element will proceed with the execution of this research pathway with the goal of gathering as much data, and learning as much as possible, to provide a safe and effective pharmaceutical formulary for use during exploration missions.
Spectra or similar Ultra-high-molecular-weight polyethylene (UHMWPE) fabric is the likely choice for future structural space suit restraint materials due to its high strength-to-weight ratio, abrasion resistance, and dimensional stability. During long duration space missions, space suits will be subjected to significant amounts of high-energy radiation from several different sources. To insure that pressure garment designs properly account for effects of radiation, it is important to characterize the mechanical changes to structural materials after they have been irradiated. White Sands Test Facility (WSFTF) collaborated with the Crew and Thermal Systems Division at the Johnson Space Center (JSC) to irradiate and test various space suit materials by examining their tensile properties through blunt probe puncture testing and single fiber tensile testing after the materials had been dosed at various levels of simulated GCR and SPE Iron and Proton beams at Brookhaven National Laboratories. The dosages were chosen based on a simulation developed by the Structural Engineering Division at JSC for the expected radiation dosages seen by space suit softgoods seen on a Mars reference mission. Spectra fabric tested in the effort saw equivalent dosages at 2x, 10x, and 20x the predicted dose as well as a simulated 50 year exposure to examine the range of effects on the material and examine whether any degradation due to GCR would be present if the suit softgoods were stored in deep space for a long period of time. This paper presents the results of this work and outlines the impact on space suit pressure garment design for long duration deep space missions.