INTRODUCTION: Rapid onset, noninjection methods are required to provide “as needed” therapy for motion sickness. Intranasal scopolamine (IN SCOP) is attractive because it can be fast acting and work when gastric motility is slowed. Intranasal administration can provide a time to maximal concentration (T_max) of drugs (e.g., naloxone and midazolam) of 30 min or less. We evaluated the efficacy, pharmacodynamics, and pharmacokinetics of IN SCOP in a placebo-controlled, randomized, double-blind, dose-ranging study, and compared pharmacokinetic outcomes against other published results.METHODS: There were 18 healthy adult volunteers (10 M, 8F) who received placebo, low dose (0.2 mg), and high dose (0.4 mg) IN SCOP intranasally using a pump device and a gel formulation. Participants rode in an off-vertical axis rotation (OVAR) chair 1.25 h after dose administration and completed neurocognitive tests to evaluate secondary drug impacts. Pharmacokinetics (PK) and pharmacodynamics (PD) were assessed in eight subjects. PK data were compared to results from previously published studies.RESULTS: Low and high dose IN SCOP increased chair time significantly compared to placebo. No significant sleepiness or cognitive impairment was seen, likely due to the small sample size. T_max was long for both dosages (High dose 75.0 ± 49.4 min, Low dose 61.9 ± 37.1 min), compared to other intranasally administered drugs and some previous studies with IN SCOP. Average T_max was not superior to previously published values for dose-matched (0.4–0.5 mg), orally-delivered SCOP.DISCUSSION: IN SCOP has potential as a rapid administration route for relieving MS symptoms, but more work is needed to identify optimal intranasal formulation and dispensing methods.KEYWORDS: Motion sickness, pharmacokinetics, scopolamine, intranasal administration.Stankovic AS, Alvarenga DL, Daniels VRC, Simmons RG, Buckey JC, Putcha L. Intranasal scopolamine for motion sickness. Aerosp Med Hum Perform. 2019; 90(11):917–924.

BACKGROUND: UK Royal Air Force fast jet aircrew use three different anti-G systems, however, little objective comparison of the G protection they provide exists. The G-protection afforded by each system and associated hemodynamic responses were investigated.METHODS: Ten subjects performed centrifuge acceleration exposures using Mk-10 (S1) and Mk-4 (S2) five-bladder anti-G trousers (AGT) and full coverage AGT plus pressure breathing for G-protection (PBG; S3). Measurements of relaxed G tolerance (RGT), eye-level blood pressure (BP_eye), lower body blood volume (LBV), stroke volume (SV) and total peripheral resistance (TPR) were made during gradual onset runs (GOR) and rapid onset runs (ROR). The subjective effort required to maintain clear vision at +7 and +8 G_z provided an indication of the protection provided by the system.RESULTS: All systems moderated decreases in SV and BP_eye and increases in LBV under increased +G_z. S3 provided the greatest mean RGT during GOR (+6.2 G_z) and ROR (+6 G_z), reduced the effort required to maintain clear vision at up to +8 G_z, prevented venous pooling and afforded the greatest rise in TPR. The majority of indices revealed no difference between S1 and S2 although RGT during the ROR was greater with S2 (+0.25 G_z).DISCUSSION: S3 effectively prevented pooling of blood in the lower limbs under +G_z, despite the use of PBG, and offers an advantage over five-bladder AGT. Given the similarities of S1 and S2, it was unsurprising that the majority of indices measured were similar. The objective measurement of hemodynamic parameters provides useful information for comparing the G-protection provided by anti-G systems.Pollock RD, Firth RV, Storey JA, Phillips KE, Connolly DM, Green NDC, Stevenson AT. Hemodynamic responses and G protection afforded by three different anti-G systems. Aerosp Med Hum Perform. 2019; 90(11):925–933.

INTRODUCTION: Restless legs syndrome (RLS) is characterized by an uncomfortable sensation on the legs, which causes the urge to move the legs. The main cause is unknown but there are many risk factors, including geographical properties and high altitude. Our objective was to explore the frequency of RLS in aircrew.METHODS: There were 301 Turkish aircrew who were admitted to Istanbul Medipol University Hospital Neurology Department for periodic examinations and 272 healthy (non-aircrew) subjects included in the study. The International RLS Study Group's Questionnaire and the International RLS Study Group Rating Scale (IRLSSGRS) were used to evaluate RLS. The participants filled the RLS questionnaire and then both groups were divided into two subgroups as having RLS or not. The subjects years in the profession, average flight duration in a month, daily sleep duration, smoking, and coffee consumption were recorded. None of the subjects had previously been diagnosed with RLS.RESULTS: The frequency of RLS was 6.7% in the aircrew group and 7.9% in the control group, and there was no significant difference between the two groups. Age, gender, daily duration of sleep, smoking, coffee consumption, family history of RLS, being a pilot or a flight attendant, years in profession, and monthly flight hours were similar in aircrew with and without RLS.DISCUSSION: The RLS frequency in aircrew was similar to that of the control group. We can conclude flying at high altitude wasnt a risk factor for RLS.Düz OA, Yilmaz NH, Olmuscelik O. Restless legs syndrome in aircrew. Aerosp Med Hum Perform. 2019; 90(11):934937.

INTRODUCTION: The value of aeromedical certification in reducing adverse medical outcomes is an especially important question for this era of increasing flight operations that do not require an FAA medical certificate. The study of this question has previously been thwarted by a lack of information about pilots when their medical certificates are not renewed.METHODS: We matched airmen in the FAA medical certification database to the U.S. Social Security Death Index to identify date of death for deceased pilots. Logistic regression models were used to explore associations of certification data with odds of death while holding a medical certificate and within 4 yr of expiration of a medical certificate.RESULTS: FAA aeromedical waivers were associated with 33% lower odds of death while holding a medical certificate and 35% increased odds of death within 4 yr after expiration of a medical certificate. Denial was associated with 21% increased odds of death in the next 4 yr. Only 13 of 47 medical conditions having significant associations were associated with increased odds of death during certification.DISCUSSION: We found that FAA aeromedical certification reduces the odds of death while holding a medical certificate compared to the 4 yr after certificate expiration. We believe this helps provide a positive answer to the question of whether medical certification reduces medically related events.Mills WD, Greenhaw RM. Association of medical certification factors with all-cause mortality in U.S. aviators. Aerosp Med Hum Perform. 2019; 90(11):938–944.

BACKGROUND: The work schedules of airline crewmembers include extended workdays, compressed work periods, and limited time for recovery, which may lead to cardiovascular strain and fatigue. The aim of this study was to evaluate changes in heart rate variability (HRV) during work and sleep, and with respect to work characteristics and breaks.METHODS: We followed 49 airline crewmembers during four consecutive workdays of ≥39 h. Data included HRV measurements, a questionnaire, and sleep/work diaries. HRV parameters include root mean square of successive differences (RMSSD), standard deviation of the normal beat-to-beat differences (SDNN), and the low and high frequency ratio (LF/HF).RESULTS: The results indicate higher levels of cardiovascular strain on the 4th compared to the 1st workday, most prominent among cabin crewmembers. In this group, we observed indications of decreased cardiovascular strain by increasing duration of sleep, demonstrated by increased RMSSD (B = 2.7, 95% CI 1.6, 3.8) and SDNN (B = 4.4, 95% CI 3.0, 5.7), and decreased LF/HF (B = −0.2, 95% CI, −0.4,−0.01). Similarly, longer duration of breaks was associated with lower cardiovascular strain, indicated by increased RMSSD (B = 0.1, 95% CI 0.03, 0.1) and SDNN (B = 0.1, 95% CI 0.1, 0.1). Among pilots, increased LF/HF indicated higher cardiovascular strain in those who often or always reported of high workload (B = 4.3, 95% CI 2.3, 6.3; and B = 7.3, 95% CI 3.2, 11.4, respectively).DISCUSSION: The results support the contention that the studied work period increases cardiac strain among airline crew. Work characteristics, breaks, and sleep are associated with changes in HRV.Goffeng EM, Nordby K-C, Tarvainen M, Järvelin-Pasanen S, Wagstaff A, Skare Ø, Lie J-A. Cardiac autonomic activity in commercial aircrew during an actual flight duty period. Aerosp Med Hum Perform. 2019; 90(11):945–952.

BACKGROUND: Actual studies in military training support the use of new methodological approaches such as high intensity interval training and inverse periodization training rather than conventional approaches. However, the application and analysis of success of these new methodologies are as yet unknown.METHODS: The military adapted the civil reverse periodization training system, composed of 6 wk and five sessions per week. For the first 3 wk soldiers performed two sessions with the objective of increasing the maximal strength of the upper and lower body muscles, and three sessions of short high-intensity interval training (HIIT). In the following 3 wk they combined two endurance HIIT and two resistance HIIT sessions with military equipment while conducting a military task.RESULTS: After the training a significant body mass index decrease was found, along with an increase in lower limb muscular strength, aerobic and anaerobic performance, resilience, stress tolerance, and psychological flexibility. Regarding the ratio of acceptance there was an increased ratio compared to previous years of 7%. In addition, married soldiers with children presented greater resilience, stress tolerance, psychological flexibility, and a higher ratio of success.DISCUSSION: Accepted soldiers presented greater psychological status and stress tolerance, highlighting the importance of the work of the unit psychologists to reinforce and monitor the psychometric profile of the soldiers as well as their intrinsic characteristics of personality and emotionality. The greater baseline physical condition and higher performance in all physical tests proves how reverse periodization training models are a great stimuli and training approach in soldiers.Tornero-Aguilera JF, Gregório Pelarigo J, Clemente-Suarez VJ. Psychophysiological intervention to improve preparedness in military Special Operations forces. Aerosp Med Hum Perform. 2019; 90(11):953–958.

INTRODUCTION: Exposure to high G force is a known safety hazard in military aviation as well as civilian aerobatic flight. Tolerance to high G forces has been well studied in military pilots, but there is little research directed at civilian pilots who may have medications or medical conditions not permitted in military pilots.METHODS: In this case-control study, we identified 89 fatal high-G aerobatic accidents and 4000 fatal control accidents from 1995 through 2018 from the NTSB accident database and the FAA autopsy database. We retrieved medications and medical conditions from the FAA's pilot medical databases. Logistic regression models were used to explore the associations of drugs, medical conditions, height, and medical waivers with high-G accidents.RESULTS: Seven drugs (alprazolam, clonidine, ethanol, meclizine, phentermine, triamterene, and zolpidem) reached statistical significance in our models, but had such small case counts that we consider these findings to be uncertain, except for ethanol, which was found in seven cases. Of these, only triamterene was known to the FAA. Statistically significant medical predictors included only alcohol abuse (seven cases) and liver disease (only two cases).DISCUSSION: Our analysis found that the drug ethanol and the condition alcohol abuse are significantly associated with high-G accidents. Seven other factors were statistically significant, but should only be considered as hypothesis generating due to very low case counts. Our study does not suggest that restricting pilots with otherwise permissible medications or medical conditions from aerobatics is warranted.Mills WD, Greenhaw RM, Wang JMP. A medical review of fatal high-G U.S. aerobatic accidents. Aerosp Med Hum Perform. 2019; 90(11):959–965.

INTRODUCTION: Analysis of historical solar particle events (SPEs) provides context for some understanding of acute radiation exposure risk to astronauts who will travel outside of low-Earth orbit. Predicted levels of radiation exposures to exploration crewmembers could produce some health impacts, including nausea, emesis, and fatigue, though more severe clinical manifestations are unlikely. Using current models of anticipated physiological sequelae, we evaluated the clinical challenges of managing radiation-related clinical concerns during exploration spaceflight.METHODS: A literature review was conducted to identify terrestrial management standards for radiation-induced illnesses, focusing on prodromal symptom treatment. Terrestrial management was compared to current spaceflight medical capabilities to identify gaps and highlight challenges involved in expanding capabilities for future exploration spaceflight.RESULTS: Current spaceflight medical resources, such as those found on the International Space Station, may be sufficient to manage some aspects of radiation-induced illness, although effective treatment of all potential manifestations would require substantial expansion of capabilities. Terrestrial adjunctive therapies or more experimental treatments are unavailable in current spaceflight medical capabilities but may have a role in future management of acute radiation exposure.DISCUSSION: Expanded medical capabilities for managing radiation-induced illnesses could be included onboard future exploration vehicles. However, this would require substantial research, time, and funding to reach flight readiness, and vehicle limitations may restrict such capabilities for exploration missions. The benefits of including expanded capabilities should be weighed against the likelihood of significant radiation exposure and extensive mission design constraints.Blue RS, Chancellor JC, Suresh R, Carnell LS, Reyes DP, Nowadly CD, Antonsen EL. Challenges in clinical management of radiation-induced illnesses during exploration spaceflight. Aerosp Med Hum Perform. 2019; 90(11):966–977.

BACKGROUND: Although oropharyngeal squamous cell papilloma (OSCP) is not uncommon in the general population, reports of OSCP in aviators are rare. This case report serves as a call for flight surgeons to consider all oropharyngeal pathology as a potential source of airway compromise during flight, and highlights regional risk factors for developing malignancies of the oropharynx.CASE REPORT: A 24-yr-old male foreign national student aviator from a central Asian country was at Fort Rucker for flight training. He presented to the clinic with a chief complaint of sore throat and cough for 2 d. He was afebrile but reported a history of a “throat” mass which was previously evaluated by a U.S. military otolaryngologist. Said mass was approximately 0.5 cm × 0.5 cm, irregular appearing, inflamed, and protruding from the inferior aspect of the right tonsil. Previous biopsy report revealed a squamous cell papilloma and, after consideration of the pilot’s training program, active surveillance of the lesion was mutually agreed upon until the student’s training had concluded and definitive excision was performed.DISCUSSION: A robust history and physical exam including an occupational, social, and environmental exposure history is crucial to diagnosis. Foreign national patients often have unique backgrounds that merit consideration when developing a differential diagnosis, assessment, and plan. In the field of Flight Medicine, a patient’s occupational demands are essential to his or her care. In particular, any potential obstruction of the airway during flight must be considered, even if a pathology does not represent an immediate threat to the pilot’s health.Swinson K, Burlile J, Pavelites J. Squamous cell papilloma in a student aviator. Aerosp Med Hum Perform. 2019; 90(11):978–981.

INTRODUCTION: During the Cold War years, the Space Race was largely supported by the efforts of many engineers and scientists, in particular human physiologists. Rodolfo Margaria (1901–1983), director of the Institute of Human Physiology at the University of Milan, was one of the most eminent and focused his studies on the mechanics of human locomotion in subgravity, in particular on the Moon’s surface. Long before the real Moon landing, Margaria was able to correctly theorize how astronauts would walk on lunar soil, what would be the optimal pattern of progression, as well as determine the optimum and maximum speed at one-sixth of the Earth's gravity. On 21^st July 1969 at 02:56 UTC, great excitement was aroused by the television images of Neil Armstrong's first steps on the Moon. Instead of walking, he moved around making small leaps, as expected from Margaria and colleagues.Grasso GS, Beretta EP, Miserocchi GA, Riva MA. Rodolfo Margaria and the first walk on the Moon. Aerosp Med Hum Perform. 2019; 90(11):982–985.

Long AM. You’re the flight surgeon: eosinophilic esophagitis. Aerosp Med Hum Perform. 2019; 90(11):986–988.