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Improving Efficacy and Safety of Pharmacological Treatment Through Precision Health and Pharmacogenomics

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expand in duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to tailor medications for individual crewmembers and further examine appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique clinical and environmental history, genetic makeup, and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. A subset of this field is pharmacogenomics (PGX), the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on drug choice and dosing to avoid adverse events and maximize efficacy. The study goal was to identify which current space pharmacy drugs could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs on the ISS was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both astronauts’ personal medications, including supplements and over the counter drugs (n=151) contained in the ISS medical accessory kit (IMAK), and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in a total of 157 drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure (LxC). Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent ineffective treatment or impactful side effect events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost, or technical criteria and ranked from 1 (very low) to 5 (very high). An assessment of PGX reference laboratories is currently underway to evaluate sample requirements, benefit analysis (cost vs. utility of allele variant analysis), relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments (LxC 5x5 table) indicated 128 medications were in the green zone where risk is acceptable, with the remaining 29 of the medications in the yellow or red zone driven predominantly due to drug failure or safety concerns. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive preflight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve drug efficacy, and further open the door to countermeasure research. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more effective and efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing selection of the best treatment choice, and providing tailored countermeasures for individual crewmembers.

Pharmacogenomics↗

Improving Efficacy and Safety of Pharmacological Treatment Through Precision Medicine and Pharmacogenomics for Human Deep Space Exploration

INTRODUCTION: Future spaceflight will require increased crew medical autonomy as exploration class missions expanding duration and distance from Earth, especially for Mars missions. As mission duration increases, it will be even more essential to have appropriate amounts of effective medication to ensure the maintenance of crew health and performance. Conversely, mass and volume constraints will become more severe as future spaceflight expands beyond low Earth orbit, where resupply is difficult or becomes impossible. These constraints thus convey an urgency to further tailor medications included in the spacecraft formulary and increased examination of appropriate dosing regimens. BACKGROUND: Precision Health is an exciting area of cutting-edge research and medicine focused on maintaining an individual’s health and performance through in-depth understanding of an individual’s unique factors and molecular profiles. This approach can be adapted to better predict, monitor, and address physiological responses to the spaceflight environment. One example is the field of pharmacogenomics (PGX),the study of how the expressed genome impacts drug responses with the goal of prescribing the right dose of the right drug at the right time. Specifically, PGX testing provides valuable information on an individual’s precise allelic variations to guide physicians in making informed decisions on pharmaceutical choice and dosing to avoid adverse drug events and maximize pharmacological efficacy. The goal of this study was to evaluate which drugs in the current space pharmacy could be evaluated using PGX testing and to understand the potential impact on the health and wellness of the astronaut population. Additionally, we sought to evaluate clinically available FDA-approved PGX testing solutions to better understand its applicability. METHODS: A complete list of drugs onboard the International Space Station (ISS) was analyzed for risk and likelihood of drug failure and PGX actionability. This analysis encompassed both personal astronaut medications, including supplements and over the counter drugs (n=151) and ISS MedKit formulary medications (n=95). Duplicate medications and different formulations were removed, which resulted in 157 total drugs used in the subsequent analysis. A 5x5 risk assessment table was produced by examining the likelihood of drug failure compared to the consequence of drug failure. Likelihood of individual drug failure was defined by whether existing processes are sufficient to prevent adverse events, as ranked from 1 (very low, can easily be prevented) to 5 (very high, cannot be prevented) during a Mars mission. In contrast, the consequence of drug failure was defined by impact to safety, schedule, cost or technical and ranked from 1 (very low) to 5 (very high).A comprehensive assessment of commercially available PGX solutions is currently underway to evaluate specimen requirements, cost/benefit analysis (cost vs. number of alleles assessed), utility of variant analysis, relevance to inflight medication usage, quality of reporting in enabling clinical application, and ease of integration into electronic medical records. RESULTS: Risk assessments(LxC 5x5 table) indicated29medicationswere in the yellow or red zone driven predominantly by drug failure or safety concerns, with the remainder(n=128)of the medications in the green zone where risk is acceptable. We found that current PGX testing results could impact 21% of the total medications in the ISS MedKit and IMAK; of these, 9 medications currently have direct clinically actionable guidance available. Results of the clinical PGX solution evaluations as related to these medications will be presented. CONCLUSION: PGX testing has demonstrated clear benefits in terrestrial medicine and clinical environments for the selection of proper medications, avoiding adverse drug reactions, and maximizing drug efficacy. We propose that similar benefits would be bestowed on the astronaut and commercial spaceflight passenger population by performing preemptive pre-flight PGX testing to reduce risk of mission failure due to ineffective or toxic medications, improve targeting drug efficacy and safety, and further open the door to countermeasure research exploring PGX-related allelic variants. For example, PGX results could allow tailoring of specific medications at optimal doses more precisely to each individual astronaut, particularly in areas of space motion sickness, sleep aids, and analgesics. An additional benefit is that PGX results could provide information for better planning of the components of a space pharmacy for deep space missions to be more cost effective and more efficient in the utilization of limited pharmaceutical resources. Finally, while PGX testing of the astronaut corps is not currently conducted, this approach could provide immediate impact in support of mission success by reducing risks, optimizing astronaut performance, and providing valuable insights into long-term astronaut health. Such advancements in clinical decision making are important next steps in building dynamic individual risk profiles for astronauts, increasing crew autonomy and providing tailored countermeasures

Alice R W Tang↗

Crew-Centered Operations: What HAL 9000 Should Have Been

To date, manned space flight has maintained the locus of control for the mission on the ground. Mission control performs tasks such as activity planning, system health management, resource allocation, and astronaut health monitoring. Future exploration missions require the locus of control to shift to on-board due light speed constraints and potential loss of communication. The lunar campaign must begin to utilize a shared control approach to validate and understand the limitations of the technology allowing astronauts to oversee and direct aspects of operation that require timely decision making. Crew-centered Operations require a system-level approach that integrates multiple technologies together to allow a crew-prime concept of operations. This paper will provide an overview of the driving mission requirements, highlighting the limitations of existing approaches to mission operations and identifying the critical technologies necessary to enable a crew-centered mode of operations. The paper will focus on the requirements, trade spaces, and concepts for fulfillment of this capability. The paper will provide a broad overview of relevant technologies including: Activity Planning and Scheduling; System Monitoring; Repair and Recovery; Crew Work Practices.

Korsmeyer, David J.↗

Baseline characteristics of different strata of astronaut corps

The Longitudinal Study of Astronaut Health (LSAH) is an epidemiological study designed to study the effects of the occupational exposures incurred by astronauts in health outcomes and changes in physiological variables. Between 1959 and 1991, 195 individuals were selected for the program. The medical standards for selection have remained essentially unchanged since the Mercury Program, but the range and stringency of these criteria have been modified. Demographic and physiological variables identified during the selection year are examined for various strata of the Astronaut Corps. Specifically, age, sex, race, education, usual occupation, military affiliation, medical history, family medical history, visual and hearing measurements, physical exam variables, and specific laboratory values are investigated. Differences are examined in astronauts for the following criteria: (1) were selected prior to 1970 (n = 73) versus those selected after 1970 (n = 122); (2) have flown multiple missions versus those who have flown less than two missions; (3) have walked in space versus all others; (4) have more than 500 hours of mission time versus all others; and (5) have gone to the Moon versus all others. Length of time served in the Astronaut Corps is examined for each of these strata.

Hamm, Peggy B.↗

HRP Data Accessibility Current Status

Overview of talk: a) Content of Human Life Science data; b) Data archive structure; c) Applicable legal documents and policies; and d) Methods for data access. Life Science Data Archive (LSDA) contains research data from NASA-funded experiments, primarily data from flight experiments and ground analog data collected at NASA facilities. Longitudinal Study of Astronaut Health (LSAH) contains electronic health records (medical data) of all astronauts, including mission data. Data are collected for clinical purposes. Clinical data are analyzed by LSAH epidemiologists to identify trends in crew health and implement changes in pre-, in-, or post-flight medical care.

Sams, Clarence↗

Performance Risk Model (PRisM) Proof-of-Concept: An Operational Decision Support Tool to Predict Crew Performance in Space from Available Performance Tests

The Crew Health and Performance-Probabilistic Risk Assessment (CHP-PRA) team at NASA Glenn Research Center has developed a range of tools to evaluate astronaut health during spaceflight and to optimize the medical set required for missions. Among these, the Performance Risk Model (PRisM) represents a novel advancement, extending CHP-PRA’s focus beyond medical systems into the domain of human performance. Such tool could be pivotal in optimizing astronaut capabilities during space travel, thereby enhancing overall mission success. PRisM leverages data from well-established performance assessments conducted during previous crewed space missions and Earth analogs to strategically predict outcomes for planned tasks, even when direct performance testing has not been conducted for those specific tasks. To evaluate performance, PRisM references the various metrics outlined in NASA-STD-3001 and employs a methodology to integrate different performance scales. This framework analyzes the contribution of various human system task categories (HSTCs) to task execution and compares these contributions to the HSTCs’ involvement in other known tests. The model further employs a Monte Carlo simulation to sample performance scores from their distribution in operationally relevant tests such as those in Mulavara et al. (2018) and, by leveraging similarities in HSTC involvement, transfers this knowledge to actual mission tasks, such as those outlined in the "Human Exploration of Mars: Preliminary List of Crew Tasks”. The current PRisM proof-of-concept includes analyses of the impact of exercise and specific medications on astronauts’ performance, with provisions to incorporate additional countermeasures as data becomes available. Furthermore, the tool is customizable to include any system necessary to fully encompass the domain of human systems and can be adapted to evaluate performance for any spaceflight activities as requested by operational stakeholders. PRisM has the potential to assist the Human Research Program in exploring the capabilities trade space for optimized crew performance.

performance modeling↗

Overview of Pre-Flight Physical Training, In-Flight Exercise Countermeasures and the Post-Flight Reconditioning Program for International Space Station Astronauts

International Space Station (ISS) astronauts receive supervised physical training pre-flight, utilize exercise countermeasures in-flight, and participate in a structured reconditioning program post-flight. Despite recent advances in exercise hardware and prescribed exercise countermeasures, ISS crewmembers are still found to have variable levels of deconditioning post-flight. This presentation provides an overview of the astronaut medical certification requirements, pre-flight physical training, in-flight exercise countermeasures, and the post-flight reconditioning program. Astronauts must meet medical certification requirements on selection, annually, and prior to ISS missions. In addition, extensive physical fitness testing and standardized medical assessments are performed on long duration crewmembers pre-flight. Limited physical fitness assessments and medical examinations are performed in-flight to develop exercise countermeasure prescriptions, ensure that the crewmembers are physically capable of performing mission tasks, and monitor astronaut health. Upon mission completion, long duration astronauts must re-adapt to the 1 G environment, and be certified as fit to return to space flight training and active duty. A structured, supervised postflight reconditioning program has been developed to prevent injuries, facilitate re-adaptation to the 1 G environment, and subsequently return astronauts to training and space flight. The NASA reconditioning program is implemented by the Astronaut Strength, Conditioning, and Rehabilitation (ASCR) team and supervised by NASA flight surgeons. This program has evolved over the past 10 years of the International Space Station (ISS) program and has been successful in ensuring that long duration astronauts safely re-adapt to the 1 g environment and return to active duty. Lessons learned from this approach to managing deconditioning can be applied to terrestrial medicine and future exploration space flight missions.

Kerstman, Eric↗

Why We Do What We Do: Data Reuse, Open Access, and Privacy in Data Management at the Life Sciences Data Archive

As custodian of the unique and irreplaceable collections of human subject research data generated by the Human Research Program and its predecessors throughout the agency’s history, the Life Sciences Data Archive (LSDA) is charged with protecting participants’ privacy and implementing their consent decisions as it provides retrospective data for use in new studies. This active, stewardship-focused approach to data management and preservation shapes the products that LSDA provides to researchers and the responsibilities of researchers in using the data and publishing their results. This presentation reviews how federal and agency mandates shape LSDA’s data management procedures and expectations for researchers. Topics covered will include LSDA’s movement towards implementation of the FAIR (Findable, Accessible, Interoperable, Reusable) principles and how the archive’s evolving data management practices support FAIR-ness; collaboration between LSDA and the Lifetime Surveillance of Astronaut Health (LSAH) project (the repository of astronaut medical data); LSDA’s response to the challenges of performing its stewardship role and maintaining trust given the public profiles of the subjects whose data it preserves; and the ever-increasing challenges to expectations of subject privacy stemming from the growing power and ubiquity of of data analysis and aggregation tools.

Data↗

Why We Do What We Do: Data Reuse, Open Access and Privacy in Data Management at the Life Sciences Data Archive

As custodians of the unique and irreplaceable collections of human subject research data generated by the Human Research Program and its predecessors throughout the agency’s history, the Life Sciences Data Archive (LSDA) is charged with protecting participants’ privacy and implementing their consent decisions as it provides retrospective data for use in new studies. This active, stewardship-focused approach to data management and preservation shapes the products that LSDA provides to researchers and the responsibilities of researchers in using the data and publishing their results. This presentation reviews how federal and agency mandates shape LSDA’s data management procedures and expectations for researchers. Topics covered will include LSDA’s movement towards implementation of the FAIR (Findable, Accessible, Interoperable, Reusable) principles and the archive’s evolving data management practices; collaboration between LSDA and the Lifetime Surveillance of Astronaut Health (LSAH) project (the repository of astronaut medical data); LSDA’s response to the challenges of performing its stewardship role and maintaining trust given the public profiles of the subjects whose data it preserves; and the ever-increasing challenges to expectations of subject privacy stemming from the growing power and ubiquity of data analysis and aggregation tools.

data management↗

Preparing for Planetary Surface Exploration by Measuring Habitat Dust Intrusion with Filter Tests During an Analogue Mars Mission

As humans venture deeper into space more issues related to operations will become apparent. While the perils ofdust particles may not be widely recognized, it is one of the major issues astronauts will face on the surface of theMoon and Mars. Dust particles present a problem for both astronaut health and equipment as revealed during theApollo era lunar surface missions. Dust particles cling to spacesuits and field gear, which upon ingress would begincirculating throughout the spacecraft or habitat. An astronaut's health is compromised by the dust particle's potentialto embed in the lungs and cause respiratory illnesses. The extreme abrasiveness and granularity of the particles makeit near impossible to completely shield a spacecraft or habitat from dust related damage. NASA's Glenn ResearchCenter collaborated with Crew 188 at the Mars Desert Research Station (MDRS) in Utah to measure how much dustentered the habitat during a series of extravehicular activities (EVAs), or surface excursions. A NASA GRCdeveloped multistage filter system, coined the Scroll Filter System, was tested, for its effectiveness in removing dustthat entered the airlock and habitat after the EVAs. An optical particle counter measured the ambient airlockparticulates five times including: before the start of operations; after the crew left for EVA; in the middle of the EVAwith the settled air; before the crew entered the airlock after EVA; and finally, after the crew simulated repressurizationand suit brushing off in the airlock. Data was also collected in several of the working environmentlocations around MDRS and outside the habitat in the wind. Data collected from this research will help establishfilter equipment for life support systems and prescribed operations for astronaut transition from a planetary surfaceinto a desired clean habitat. Measurements may aid in updating a baseline expected dust load for a surface habitatand further facilitate the mitigation of astronaut's exposure to dust particles on the surface of celestial bodies.

Kobrick, Ryan L.↗

Numerical Characterization of Astronaut CaOx Renal Stone Incidence Rates to Quantify In-flight and Post-flight Relative Risk

Changes in urine chemistry potentially alter the risk of renal stone formation in astronauts. Quantifying spaceflight renal stone incidence risk compared to pre-flight levels remains a significant challenge for assessing the appropriate vehicle, mission, and countermeasure design. A computational biochemistry model representing CaOx crystal precipitation, growth, and agglomeration is combined with a probabilistic analysis to predict the in- and post-flight CaOx renal stone incidence risk ratio (IRR) relative to pre-flight values using 1517 astronaut 24-hour urine chemistries. Our simulations predict that in-flight fluid intake alone would need to increase from current prescriptions of 2.0 - 2.5 L/day to approximately 3.2 L/day to approach CaOx IRR of the pre-flight population. Bone protective interventions would reduce CaOx risk to pre-flight levels if Ca excretion alone is reduced to < 150 mg/day or if current levels are diminished to 190mg/day in combination with increasing fluid intake to 2.5 - 2.7 L/day. This analysis provides a quantitative risk assessment that can influence the critical balance between engineering and astronaut health requirements.

renal stones↗

International Space Station as Analog of Interplanetary Transit Vehicle For Biomedical Research

Astronaut missions lasting up to six months aboard the International Space Station (ISS) have much in common with interplanetary flights, especially the outbound, Earth-to-Mars transit portion of a Mars mission. Utilization of ISS and other appropriate platforms to prepare for crewed expeditions to planetary destinations including Mars has been the work of NASA's Human Research Program (HRP) since 2005. HRP is charged specifically to understand and reduced the risks to astronaut health and performance in space exploration missions: everything HRP does and has done is directly related to that responsibility. Two major categories of human research have capitalized on ISS capabilities. The first category centers on the biomedical aspects of long-duration exposure to spaceflight factors, including prolonged weightlessness, radiation exposure, isolation and confinement, and actual risk to life and limb. These studies contribute to astronaut safety, health and efficiency on any long-duration missions, whether in low Earth orbit (LEO) or beyond. Qualitatively, weightlessness is weightlessness, whether in LEO or en route to Mars. The HRP sponsors investigations into losses in muscle and bone integrity, cardiovascular function, sensory-motor capability, immune capacity and psychosocial health, and development and demonstration of appropriate treatments and preventative measures. The second category includes studies that are focused on planetary expeditions beyond LEO. For these, ISS offers a high fidelity analog to investigate the combined effects of spaceflight factors (described above) plus the isolation and autonomy associated with simulated increasing distance from Earth. Investigations address crew cohesion, performance and workload, and mission control performance. The behavioral health and performance and space human factors aspects of planetary missions dominate this category. Work has already begun on a new investigation in this category which will examine the effects of a simulated lag in communications (mimicking that expected in transit to Mars) on astronaut performance aboard ISS. Extension of the current ISS increment duration from six months to nine or even twelve months would provide opportunities for expanded research relevant to long duration missions, albeit at the cost of fewer astronauts as subjects for those investigations. Given the possible limited access to ISS after 2020, if ISS is intended to facilitate future exploration missions, then the in-flight human investigations should focus on those that clearly enable future exploration missions.

Charles, John B.↗

Spaceflight Human System Standards

NASA created a new approach for human system integration and human performance standards. NASA created two documents a standard and a reference handbook. The standard is titled NASA Space Flight Human-System Standard (SFHSS) and consists of two-volumes: Volume 1- Crew Health This volume covers standards needed to support astronaut health (medical care, nutrition, sleep, exercise, etc.) Volume 2 Human Factors, Habitability and Environmental Health This volume covers the standards for system design that will maintain astronaut performance (ie., environmental factors, design of facilities, layout of workstations, and lighting requirements). It includes classic human factors requirements. The new standards document is written in terms so that it is applicable to a broad range of present and future NASA systems. The document states that all new programs prepare system-specific requirements that will meet the general standards. For example, the new standard does not specify a design should accommodate specific percentiles of a defined population. Rather, NASA-STD-3001, Volume 2 states that all programs shall prepare program-specific requirements that define the user population and their size ranges. The design shall then accommodate the full size range of those users. The companion reference handbook, Human Integration Design Handbook (HIDH), was developed to capture the design consideration information from NASA-STD-3000, and adds spaceflight lessons learned, gaps in knowledge, example solutions, and suggests research to further mature specific disciplines. The HIDH serves two major purposes: HIDH is the reference document for writing human factors requirements for specific systems. HIDH contains design guidance information that helps insure that designers create systems which safely and effectively accommodate the capabilities and limitations of space flight crews.

Holubec, Keith↗

Performance Risk Model Validation with Operationally Relevant Tasks

Human Research Program aims to develop methods to support astronauts’ health and productivity during spaceflight. The Crew Health and Performance Probabilistic Risk Assessment (CHP-PRA) team uses powerful computational methods to predict mission risk in both domains: medical and performance. Here, we show how CHP-PRA uses the Performance Risk Model (PRisM) to quantify the performance risk and show an application of the model on operationally relevant tasks. There are various metrics adopted across performance researchers that PRisM can accommodate. For data analysis, interpretation, and integration, we use a method of unifying data from multiple sources by converting each to a single metric. We consult subject matter experts prior to integrating the converted data into PRisM. The method we use is inspired by the Cooper-Harper rating scale [1]. Using this unified metric, we can easily combine data from various tests and lab groups. We explain our conversion method in detail and show how it pertains to the process of testing and validation of PRisM on operational tasks. We conducted an initial validation in collaboration with the Behavioral Health and Performance (BHP) lab. We test PRisM using data on their operationally relevant task ROBoT-r, a track-and-capture task for grappling incoming resupply vehicles [2]. Several other labs at NASA Johnson Space Center worked together to design 7 Functional Task Tests (FTTs) in pursuit of simulating the tasks required after landing on a planetary surface and after return to Earth [3]. Here we use the results from both ROBoT-r and the 7 FTTs and compare their experiment data to PRisM’s computational output to demonstrate how PRisM can support operations by predicting crew performance on future missions.

performance modeling↗

Space radiation and cataracts in astronauts

For over 30 years, astronauts in Earth orbit or on missions to the moon have been exposed to space radiation comprised of high-energy protons and heavy ions and secondary particles produced in collisions with spacecraft and tissue. Large uncertainties exist in the projection of risks of late effects from space radiation such as cancer and cataracts due to the paucity [corrected] of epidemiological data. Here we present epidemiological [corrected] data linking an increased risk of cataracts for astronauts with higher lens doses (>8 mSv) of space radiation relative to other astronauts with lower lens doses (<8 mSv). Our study uses historical data for cataract incidence in the 295 astronauts participating in NASA's Longitudinal Study of Astronaut Health (LSAH) and individual occupational radiation exposure data. These results, while preliminary because of the use of subjective scoring methods, suggest that relatively low doses of space radiation may predispose crew to [corrected] an increased incidence and early appearance of cataracts.

NASA Center JSC↗

Assessing the Effect of Spaceflight on the Propensity for Astronauts to Develop Disk Herniation

BACKGROUND: A previous study [1] reported that the instantaneous risk of developing a Herniated Nucleus Pulposus (HNP) was higher in astronauts who had flown at least one mission, as compared with those in the corps who had not yet flown. However, the study only analyzed time to HNP after the first mission (if any) and did not account for the possible effects of multiple missions. While many HNP's occurred well into astronauts' careers or in some cases years after retirement, the higher incidence of HNPs relatively soon after completion of space missions appears to indicate that spaceflight may lead to an increased risk of HNP. The purpose of this study was to support the Human System Risk Board assessment of back pain, evaluate the risk of injury due to dynamic loads, and update the previous dataset which contained events up to December 31, 2006. METHODS: Data was queried from the electronic medical record and provided by the Lifetime Surveillance of Astronaut Health. The data included all 330 United States astronauts from 1959 through February 2014. Cases were confirmed by Magnetic Resonance Imaging, Computerized Tomography, Myelography, operative findings, or through clinical confirmation with a neurologist or neurosurgeon. In this analysis, astronauts who had an HNP at selection into the corps or had an HNP diagnosis prior to their first flight were excluded. The statistical challenges in using the available data to separate effects of spaceflight from those associated with general astronaut training and lifestyle on propensity to develop HNPs are many. The primary outcome is reported date of first HNP (if any), which at best is only an approximation to the actual time of occurrence. To properly analyze this data with a survival analysis model, one must also know the "exposure" time - i.e. how long each astronaut has been at risk for developing an HNP. If an HNP is reported soon after a mission, is it mission caused or general? If the former, exposure time should be counted from the time of landing (assuming the risk of HNP occurring during a mission is zero). If the latter, exposure time should be counted from the time of selection; however we can't directly know which one to use. In our analysis we take both of these possibilities into account with a competing risks model, wherein two distinct stochastic processes are going on: TG = time to HNP (general) and TS = time to HNP (spaceflight). Under this type of model, whichever of these occurs first is what we observe; in other words we don't observe TG or TS, only min(TG, TS). Here, we parameterized the model in terms of separate Weibull hazard functions for each process and estimated all parameters using maximum likelihood. In addition, we allowed for a "cured fraction" - i.e. the possibility that some astronauts may never develop an HNP. RESULTS: Results will include a depiction of the competing hazard functions as well as a probability curve for the relative likelihood that an HNP reported at a given time after a mission is actually mission caused. Other factors, such as dwell time in microgravity and vehicle landing environment will be explored. An overall assessment as to whether spaceflight truly exacerbates HNP risk will be made.

Feiveson, A. H.↗