Association of Sickle Cell Trait on Career and Operational Outcomes in the United States Air Force.

INTRODUCTION: Sickle cell trait (SCT) is a heterozygotic state defined by having one normal hemoglobin gene and one sickle hemoglobin gene. Individuals with SCT are at increased risk for negative health outcomes during intense physical exertion, especially in hot climates and high-elevation locations, or when dehydrated. The U.S. Air Force mitigates this risk through universal screening after accession followed by education of SCT-positive airmen. Airmen who are SCT positive but remain asymptomatic are not restricted in occupation choice or deployment/duty locations based on their SCT status. Previous studies have analyzed the relationship between SCT and health and fitness outcomes. The objective of this study was to analyze the relationship between SCT and career and operational outcomes in a large cohort of airmen and secondarily to analyze the relationship between hemoglobin S (HgbS) percentage and these outcomes. METHODS: This is a retrospective cohort study of all recruits who entered U.S. Air Force (USAF) Basic Military Training (BMT) between January 2009 and December 2013. The SCT status was assessed through a sickle solubility test. Hemoglobin electrophoresis permitted subgroup analysis of SCT-positive individuals by HgbS percentage. The following career and operational outcomes were assessed: BMT graduation; retention at 4 and 6 years; promotion to the rank of staff sergeant by 4 and 6 years; overseas deployment and number of deployments within 6 years; and high-elevation assignment and cumulative months at a high-elevation assignment within 6 years. Multivariable logistic regression was used to assess all binary outcomes, controlling for age, sex, and race, to produce adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Multivariable Poisson regression was used to assess cumulative count outcomes and to produce adjusted incidence rate ratios (aIRRs) with 95% CIs. Attrition from BMT by SCT status was also assessed as a hazards function using the Kaplan-Meier approach with Cox proportional hazards. RESULTS: A total of 180,355 civilians entered USAF BMT during the 5-year surveillance period, of whom 169,837 graduated and had data available for analysis. Compared to their SCT-negative peers, SCT-positive airmen (n = 1,697) had 26% lower adjusted odds of promotion to staff sergeant within 4 years of BMT graduation (aOR = 0.74; 95% CI: 0.59-0.92) and served less time at a high-elevation assignment during their first 6 years (aIRR = 0.88; 95% CI: 0.85-0.91). The SCT status was not associated with statistically significant differences in BMT graduation, retention at 4 and 6 years, promotion to staff sergeant by 6 years, likelihood or number of overseas deployments, and likelihood of ever working at a high-elevation assignment. Retention at 4 and 6 years was inversely associated with HgbS percentage. CONCLUSIONS: SCT-positive and SCT-negative airmen had similar career and operational outcomes, with two exceptions: SCT-positive airmen were less likely to be promoted to staff sergeant within 4 years, and they spent less time at a high-elevation location during their first 6 years of service. The underlying explanation of these findings should be explored with an aim to support SCT-positive airmen and to reduce potentially unwarranted discrepancies. Efforts should continue to reduce the stigma associated with SCT.

COVID-19 Booster Vaccination in the U.S. Military, August 2021-January 2022.

INTRODUCTION: A booster dose of messenger RNA vaccine protects against severe COVID-19 outcomes. This study examined the incidence of COVID-19 booster vaccination among active-duty U.S. military servicemembers between August 2021 and January 2022, factors associated with vaccination uptake, and trends over time. METHODS: This was a retrospective cohort study of active-duty military personnel using data from the Defense Medical Surveillance System. Participants were included if they served in the active component from August 2021 through January 2022 and were eligible to receive a COVID-19 booster dose by January 2022. Adjusted hazard ratio estimates of time to booster vaccination were calculated using Cox proportional hazards regression. RESULTS: Lower booster vaccine uptake was seen in the U.S. military (25%) than among the general U.S. population at the same time (45%). Booster vaccination increased with older age, with greater education, with higher income, among women, and among those stationed overseas; it decreased with previous COVID-19 infection and use of the Janssen vaccine. There were no significant racial or ethnic disparities in booster vaccination. CONCLUSIONS: In the absence of a compulsory vaccination policy, lower booster vaccine uptake was seen among servicemembers than among the general U.S. population, particularly among members who were younger, were male, Marines, and had a previous history of infection. Low vaccination rates not only increase the risk of acute and long-term health effects from COVID-19 among servicemembers, but they also degrade the overall readiness of the U.S. military.

Evaluation of Gender Disparity in Tactical Combat Casualty Care.

INTRODUCTION: Women comprise nearly 19% of the U.S. military and now serve in almost all operational roles, increasing their risk of combat trauma and injuries.3 Data from the Joint Trauma Registry during Operation Enduring Freedom shows that battle-injured females had a higher case fatality rate at 36% compared to their male counterparts at 17%.1 The Tactical Combat Casualty Care curriculum is used to prepare battlefield medics to provide immediate care to wounded service members, but fails to address differences in the care of female versus male casualties. The students, who are presented with life-threatening injuries in simulated trauma scenarios, may be slower to assess, identify, and treat injuries in female patients as compared with male patients. MATERIALS AND METHODS: This observational program analysis was reviewed by the Uniformed Services University Human Research Protections Program and approved for execution as an exempt protocol under the provision of 32 CFR 219.104(d)(1). The study assessed the performance of male and female Mexican military personnel during a Tactical Combat Casualty Care course, using standardized trauma scenarios. Anatomically, correct male and female manikins were used to compare response time for different gender patients presenting with the same injuries. RESULTS: There was a statistically significant increase in time required to complete an initial blood sweep, identify a gunshot wound to the chest, and call for medical evacuation when treating a female patient compared to a male patient. CONCLUSIONS: A lack of female representation in trauma training may have contributed to the higher case fatality rate of female soldiers compared to male soldiers during Operation Enduring Freedom. Female live actors and Gender Retrofit Kits can augment trauma casualty assessment and treatment training scenarios and better prepare our forces to respond to life-threatening emergencies.

Varicella seroepidemiology in United States air force recruits: A retrospective cohort study comparing immunogenicity of varicella vaccination and natural infection.

BACKGROUND/OBJECTIVES: Infection with varicella zoster virus (VZV) produces lifelong immunity, but duration of post-vaccination immunity has not been established. The purpose of this study is to determine if a difference exists in the long-term seropositivity of anti-VZV antibodies in a cohort of young adults who were vaccinated against varicella as compared to a similar cohort with a history of chickenpox disease, and to determine which variables best predict waning seropositivity following varicella vaccination. METHODS: This retrospective cohort study captures immunization and serology data from approximately 10,000 recruits who entered basic military training between January 1, 2008, and December 31, 2015, and who have childhood immunization records in the Air Force Aeromedical Services Information Management System. Varicella vaccine immunogenicity was determined relative to the immunogenicity of chickenpox disease, as measured by multiplex flow immunoassay. Among vaccine recipients, waning seroimmunity was modeled and adjusted for several important covariates. RESULTS: Basic military trainees who received varicella vaccine in childhood were 24% less likely to be seropositive to VZV than trainees who were exempt from vaccine due to a history of chickenpox disease. There was no significant difference in seropositivity between male and female trainees. The odds of a vaccinated trainee being seropositive to VZV decreased by 8% with each year elapsed since vaccination. Seroprevalence declined below estimated herd immunity thresholds in vaccinated trainees born after 1994, and in the cohort as a whole for trainees born after 1995. CONCLUSION: Despite prior vaccination, seroimmunity in a large cohort of young adults unexposed to wild-type VZV failed to meet the estimated threshold for herd immunity. If vaccination in accordance with the current US VZV vaccination schedule is inadequate to maintain herd immunity, young adults not previously exposed to wild-type VZV may be at increased risk for varicella outbreaks.

Measles, Mumps, and Rubella Titers in Air Force Recruits: Below Herd Immunity Thresholds?

INTRODUCTION: Preventable diseases like measles and mumps are occurring with increasing frequency in the U.S. despite the availability of an effective vaccine. Given concern that an outbreak may occur among military recruits, we compared serologic evidence of immunity to measles, mumps, and rubella among military recruits with known herd immunity thresholds and determined whether the current Department of Defense policy of presuming mumps immunity based on measles and rubella titers is reliable. METHODS: Serum antibody levels for measles, mumps, and rubella were obtained from all new recruits upon arrival at Joint Base San Antonio-Lackland, Texas, from 25 April 2013 through 24 April 2014. Seroprevalence of each disease was assessed by age and sex, and concordance between mumps titers and measles and rubella titers was calculated. Data analysis was performed in 2014-2015. RESULTS: Among 32,502 recruits, seroprevalences for measles, mumps, and rubella antibodies were 81.6%, 80.3%, and 82.1%, respectively. Of the 22,878 recruits seropositive for both measles and rubella antibodies, 87.7% were also seropositive for mumps. CONCLUSIONS: Seroprevalences for measles, mumps, and rubella antibodies among a large cohort of recruits entering U.S. Air Force basic training were generally lower than levels required to maintain herd immunity. In order to reduce the incidence of mumps infections, the Department of Defense should consider obtaining antibody titers for measles, mumps, and rubella and vaccinating all individuals susceptible to one or more of the viruses.

The value of all-payer claims databases to states.

All-payer claims databases are being developed in states across the nation to fill gaps in information about the health care system. The value of such databases is becoming more apparent as these databases mature and are used more frequently to help states better understand their health care utilization and costs.

Mental health diagnoses during the year prior to schizophrenia, U.S. Armed Forces, 2001-2010.

Identification of military members in the prodromal phase of schizophrenia may lead to earlier treatment and allow non-urgent transition away from military duties. This report documents the incidence of schizophrenia in the U.S. military and summarizes mental health diagnoses during the year prior to initial clinical diagnoses schizophrenia. During 2001-2010, 3,000 service members met the case definition of schizophrenia (incidence rate: 21 per 100,000 person-years). Rates declined with increasing age. Of those diagnosed with schizophrenia, 71% had at least one mental health-related medical encounter during the preceding 12 months; 51% received at least one antecedent diagnosis of paranoia. The findings may inform a model to predict the likelihood and timing of clinical manifestations of schizophrenia among U.S. military members.

Association of chronic alcohol consumption and increased susceptibility to and pathogenic effects of pulmonary infection with respiratory syncytial virus in mice.

Chronic alcohol abuse by human beings has been shown to be associated with increased susceptibility to pulmonary infections and severity of inflammatory responses associated with pulmonary infection. On the basis of the higher likelihood of exposure to respiratory viruses, people who abuse alcohol would logically be susceptible to respiratory viral infections. To test this hypothesis, mice were provided alcohol in drinking water for 13-16 weeks with the Meadows-Cook protocol and infected intranasally with respiratory syncytial virus. At various times after infection, severity of infection was determined by evaluation of cellular and cytokine composition of bronchoalveolar lavage fluid (BALF) and histologic evaluation of inflammation. Infection was associated with neutrophil infiltration in both groups, but the proportion and number of neutrophils in BALF were significantly greater in the alcohol consumption group than in the control group. Concentrations of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 in BALF in the alcohol consumption group were increased. Interferon (IFN)-gamma concentrations were lower in the alcohol consumption group at later times of infection. Pulmonary inflammation was cleared by 3-5 days after infection in the control group. In contrast, pulmonary inflammation was evident in the alcohol consumption group after 7 days of infection, and some mice showed severe inflammation with hemorrhage and edema. IFN-alpha/beta was evident in BALF at low concentrations in the alcohol consumption group for several days after infection, and increased mRNA for IFN-alpha/beta was also evident in the alcohol consumption group. This was accompanied by the presence of virus in this group at these times of infection. Chronic alcohol consumption increased severity of pulmonary infection with a virus that naturally infects hosts by an aerosol route. Infection of mice that had consumed alcohol chronically was more severe in terms of increased proinflammatory cytokine production, inflammation, and a failure to clear the virus from the lungs.

Induced SHIP deficiency expands myeloid regulatory cells and abrogates graft-versus-host disease.

Graft-vs-host disease (GVHD) is the leading cause of treatment-related death in allogeneic bone marrow (BM) transplantation. Immunosuppressive strategies to control GVHD are only partially effective and often lead to life-threatening infections. We previously showed that engraftment of MHC-mismatched BM is enhanced and GVHD abrogated in recipients homozygous for a germline SHIP mutation. In this study, we report the development of a genetic model in which SHIP deficiency can be induced in adult mice. Using this model, we show that the induction of SHIP deficiency in adult mice leads to a rapid and significant expansion of myeloid suppressor cells in peripheral lymphoid tissues. Consistent with expansion of myeloid suppressor cells, splenocytes and lymph node cells from adult mice with induced SHIP deficiency are significantly compromised in their ability to prime allogeneic T cell responses. These results demonstrate that SHIP regulates homeostatic signals for these immunoregulatory cells in adult physiology. Consistent with these findings, induction of SHIP deficiency before receiving a T cell-replete BM graft abrogates acute GVHD. These findings indicate strategies that target SHIP could increase the efficacy and utility of allogeneic BM transplantation, and thereby provide a curative therapy for a wide spectrum of human diseases.

Cutting edge: dominance by an MHC-independent inhibitory receptor compromises NK killing of complex targets.

Inhibitory receptors that recognize MHC class I molecules regulate NK cell responses and self-tolerance. Recent evidence indicates that self-ligands not present in the MHC locus also can modulate NK function. In this study, we show that an inhibitory receptor that recognizes an MHC-independent ligand is over expressed in SHIP(-/-) mice at all stages of NK development and differentiation. Overexpression of this receptor compromises key cytolytic NK functions, including killing of allogeneic, tumor, and viral targets. These results further demonstrate the critical role that SHIP plays in regulation of the NK receptor repertoire and show that regulation of MHC-independent inhibitory receptors is crucial for NK recognition and cytolysis of complex targets.

Thyroid cancers express CD-40 and CD-40 ligand: cancers that express CD-40 ligand may have a greater risk of recurrence in young patients.

The immune response might suppress thyroid cancer recurrence. Although the factors that control this are unknown, CD-40 and CD-40 ligand might be important. To test this, we stained 36 papillary (PTC) and four follicular (FTC) thyroid carcinomas for CD-40 (n = 37) and CD-40 ligand (n = 36) and graded staining from absent (grade 0) to intense (grade 3). Follicular cells of the majority of thyroid tumors expressed CD-40 (30/37, 81%) and CD-40 ligand (15/24, 69%). Cancers from young patients (< or =21 years of age) that expressed CD-40 contained more numerous lymphocytes/high-power field (36 +/- 11) than cancers that failed to express CD-40 (4 +/- 3, p = 0.01), but there was no correlation with clinical outcome. Among young patients, CD-40 ligand expression was more intense in multifocal (1.1 +/- 0.2 vs. 0.45 +/- 0.2, p = 0.037), aggressive (1.14 +/- 0.14 vs. 0.65 +/- 0.2, p = 0.05) and recurrent tumors (1.2 +/- 0.2 vs. 0.65 +/- 0.2, p = 0.05) and associated with reduced disease-free survival (p = 0.03). We conclude that the majority of thyroid cancers express CD-40 and CD-40 ligand. In patients < or =21 years of age, tumors with intense expression of CD-40 ligand are more often multifocal, aggressive, and recurrent.