Comparing Physician and Artificial Intelligence Chatbot Responses to Patient Questions Posted to a Public Social Media Forum.

Importance: The rapid expansion of virtual health care has caused a surge in patient messages concomitant with more work and burnout among health care professionals. Artificial intelligence (AI) assistants could potentially aid in creating answers to patient questions by drafting responses that could be reviewed by clinicians. Objective: To evaluate the ability of an AI chatbot assistant (ChatGPT), released in November 2022, to provide quality and empathetic responses to patient questions. Design, Setting, and Participants: In this cross-sectional study, a public and nonidentifiable database of questions from a public social media forum (Reddit's r/AskDocs) was used to randomly draw 195 exchanges from October 2022 where a verified physician responded to a public question. Chatbot responses were generated by entering the original question into a fresh session (without prior questions having been asked in the session) on December 22 and 23, 2022. The original question along with anonymized and randomly ordered physician and chatbot responses were evaluated in triplicate by a team of licensed health care professionals. Evaluators chose "which response was better" and judged both "the quality of information provided" (very poor, poor, acceptable, good, or very good) and "the empathy or bedside manner provided" (not empathetic, slightly empathetic, moderately empathetic, empathetic, and very empathetic). Mean outcomes were ordered on a 1 to 5 scale and compared between chatbot and physicians. Results: Of the 195 questions and responses, evaluators preferred chatbot responses to physician responses in 78.6% (95% CI, 75.0%-81.8%) of the 585 evaluations. Mean (IQR) physician responses were significantly shorter than chatbot responses (52 [17-62] words vs 211 [168-245] words; t = 25.4; P < .001). Chatbot responses were rated of significantly higher quality than physician responses (t = 13.3; P < .001). The proportion of responses rated as good or very good quality (≥ 4), for instance, was higher for chatbot than physicians (chatbot: 78.5%, 95% CI, 72.3%-84.1%; physicians: 22.1%, 95% CI, 16.4%-28.2%;). This amounted to 3.6 times higher prevalence of good or very good quality responses for the chatbot. Chatbot responses were also rated significantly more empathetic than physician responses (t = 18.9; P < .001). The proportion of responses rated empathetic or very empathetic (≥4) was higher for chatbot than for physicians (physicians: 4.6%, 95% CI, 2.1%-7.7%; chatbot: 45.1%, 95% CI, 38.5%-51.8%; physicians: 4.6%, 95% CI, 2.1%-7.7%). This amounted to 9.8 times higher prevalence of empathetic or very empathetic responses for the chatbot. Conclusions: In this cross-sectional study, a chatbot generated quality and empathetic responses to patient questions posed in an online forum. Further exploration of this technology is warranted in clinical settings, such as using chatbot to draft responses that physicians could then edit. Randomized trials could assess further if using AI assistants might improve responses, lower clinician burnout, and improve patient outcomes.

Screening tools for predicting mortality of adults with suspected sepsis: an international sepsis cohort validation study.

OBJECTIVES: We evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana. DESIGN: Prospective cohort studies. SETTING AND PARTICIPANTS: From 2014 to 2021, participants with two or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in Cambodia and Ghana and hospitalised participants with suspected infection were enrolled in the USA. Cox proportional hazards regression was performed, and Harrell's C-statistic calculated to determine 28-day mortality prediction performance of the quick Sequential Organ Failure Assessment (qSOFA) score ≥2, SIRS score ≥3, National Early Warning Score (NEWS) ≥5, Modified Early Warning Score (MEWS) ≥5 or Universal Vital Assessment (UVA) score ≥2. Screening tools were compared with baseline risk (age and sex) with the Wald test. RESULTS: The cohorts included 567 participants (42.9% women) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia and 180 participants from Durham, North Carolina in the USA. The pooled mortality was 16.4% at 28 days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI 0.58 to 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% CI 0.64 to 0.73; p<0.001), qSOFA (C-statistic: 0.70, 95% CI 0.64 to 0.75; p<0.001), UVA score (C-statistic: 0.73, 95% CI 0.69 to 0.78; p<0.001), but not with SIRS (0.60; 95% CI 0.54 to 0.65; p=0.13). Within individual cohorts, only the UVA score in Ghana performed better than baseline risk (C-statistic: 0.77; 95% CI 0.71 to 0.83; p<0.001). CONCLUSIONS: Among the cohorts, MEWS, NEWS, qSOFA and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.

Clinical evaluation of the BioFire Global Fever Panel for the identification of malaria, leptospirosis, chikungunya, and dengue from whole blood: a prospective, multicentre, cross-sectional diagnostic accuracy study.

BACKGROUND: Acute febrile illness is a common presentation for patients at hospitals globally. Assays that can diagnose a variety of common pathogens in blood could help to establish a diagnosis for targeted disease management. We aimed to evaluate the performance of the BioFire Global Fever Panel (GF Panel), a multiplex nucleic acid amplification test performed on whole blood specimens run on the BioFire FilmArray System, in the diagnosis of several pathogens that cause acute febrile illness. METHODS: We did a prospective, multicentre, cross-sectional diagnostic accuracy study to evaluate the GF Panel. Consenting adults and children older than 6 months presenting with fever in the previous 2 days were enrolled consecutively in sub-Saharan Africa (Ghana, Kenya, Tanzania, Uganda), southeast Asia (Cambodia, Thailand), central and South America (Honduras, Peru), and the USA (Washington, DC; St Louis, MO). We assessed the performance of six analytes (chikungunya virus, dengue virus [serotypes 1-4], Leptospira spp, Plasmodium spp, Plasmodium falciparum, and Plasmodium vivax or Plasmodium ovale) on the GF Panel. The performance of the GF Panel was assessed using comparator PCR assays with different primers followed by bidirectional sequencing on nucleic acid extracts from the same specimen. We calculated the positive percent agreement and negative percent agreement of the GF Panel with respect to the comparator assays. This study is registered with ClinicalTrials.gov, NCT02968355. FINDINGS: From March 26, 2018, to Sept 30, 2019, 1965 participants were enrolled at ten sites worldwide. Of the 1875 participants with analysable results, 980 (52·3%) were female and the median age was 22 years (range 0-100). At least one analyte was detected in 657 (35·0%) of 1875 specimens. The GF Panel had a positive percent agreement for the six analytes evaluated as follows: chikungunya virus 100% (95% CI 86·3-100), dengue virus 94·0% (90·6-96·5), Leptospira spp 93·8% (69·8-99·8), Plasmodium spp 98·3% (96·3-99·4), P falciparum 92·7% (88·8-95·6), and P vivax or P ovale 92·7% (86·7-96·6). The GF Panel had a negative percent agreement equal to or greater than 99·2% (98·6-99·6) for all analytes. INTERPRETATION: This 1 h sample-to-answer, molecular device can detect common causative agents of acute febrile illness with excellent positive percent agreement and negative percent agreement directly in whole blood. The targets of the assay are prevalent in tropical and subtropical regions globally, and the assay could help to provide both public health surveillance and individual diagnoses. FUNDING: BioFire Defense, Joint Project Manager for Medical Countermeasure Systems and US Army Medical Materiel Development Activity, and National Institute of Allergy and Infectious Diseases.

Combat exposure and behavioral health in U.S. Army Special Forces.

Although combat has been found to be associated with adverse health outcomes, little is known about the impact of specific combat exposures, particularly among specialized personnel. This study examined the association of different types of combat exposures with behavioral health outcomes, and whether these associations differed by Army occupational specialization: General Purpose Forces infantrymen (n = 5,361), Ranger Qualified infantrymen (n = 308), and Special Forces personnel (n = 593). Multivariable regression models estimated the association of combat severity, type of combat event (fighting, killing, threat to oneself, death/injury of others), and type of killing with mental health disorders, trouble sleeping, and problem drinking. Combat severity, each type of combat event, and killing noncombatants were associated with adverse health outcomes after adjusting for covariates and other combat exposures. Except for trouble sleeping, these associations did not differ by occupational specialization, though the prevalence and odds of outcomes were generally lower for Special Forces personnel.

Behavioral health and sleep problems among US Army veterinarians and veterinary technicians participating in the Millennium Cohort Study.

OBJECTIVE: To determine the prevalences and relative odds of mental health problems, suicidal ideation, psychotropic medication use, problem drinking, trouble sleeping, and lack of social support among veterinarians and veterinary technicians, compared with other medical professionals, in the US Army. SAMPLE: 7,744 US Army personnel (957 officers [101 veterinarians and 856 physicians and dentists] and 6,787 enlisted personnel [334 veterinary technicians and 6,453 medics]) participating in the Millennium Cohort Study. PROCEDURES: Eligible participants completed ≥ 1 survey while serving as an Army veterinarian, veterinary technician, physician, general dentist, or medic. Analysis methods including multivariable logistic regression adjusted for covariates and stratified by pay grade were used to investigate associations between each health-care occupation and outcomes of interest. RESULTS: Veterinarians had higher reported prevalences of mental health problems, trouble sleeping, and lack of social support than did nontrauma physicians, trauma physicians, or dentists. On multivariable analysis, veterinarians had higher odds of mental health problems, trouble sleeping, and lack of social support, compared with physicians and dentists combined; odds for these outcomes were also higher for veterinarians, compared with various individual reference groups. Veterinary technicians had lower reported prevalence and lower odds of psychotropic medication use, compared with medics. CONCLUSIONS AND CLINICAL RELEVANCE: Further examination of Army policies and organizational structures related to veterinarians may be warranted, along with the development of policies and interventions designed to improve mental health, sleep quality, and social support among military veterinarians.

Efficacy of an intramuscular bivalent norovirus GI.1/GII.4 virus-like particle vaccine candidate in healthy US adults.

BACKGROUND: We performed this first-in-human efficacy trial of Takeda's bivalent norovirus vaccine candidate (TAK-214) against moderate or severe acute gastroenteritis (AGE) in healthy adults. METHODS: This double-blind, randomized, placebo-controlled phase 2b trial was conducted over two winter seasons in 18-49 year-old US Navy recruits. Participants were randomized (1:1) to receive intramuscular injections of saline placebo (N = 2,357) or TAK-214 [15 µg GI.1 and 50 µg GII.4c VLPs, 0.5 mg Al(OH)3] (N = 2,355), and monitored for 45 days post-vaccination for AGE. Norovirus genotypes were identified by RT-PCR and sequencing of stool/vomitus samples. Sera from AGE cases were used to assess immune responses as genotype-specific histo-blood group antigen (HBGA)-blocking antibodies. FINDINGS: With low rates of homotypic norovirus AGE detected the statistical analysis was proactively modified to account for AGE due to any norovirus genotype. Of the 48 norovirus AGE cases of "any severity", 29 in placebo and 19 in vaccinees, causative genotypes were GI.1 (n = 1), G1.7a (n = 1), GII.2 (n = 39) and GII.4 (n = 7). Applying predefined definitions of moderate or severe AGE gave 26 vs. 10 cases due to any norovirus genotype in placebo vs. vaccine groups, a vaccine efficacy (VE) of 61.8% (95.01% CI, 20.8 to 81.6; p = 0.0097). Five vs. one moderate or severe cases due to vaccine GI.1/GII.4 homotypic genotypes in placebo vs. vaccine arms gave a primary endpoint vaccine efficacy of 80.0% (99.99% CI, -1318.1 to 99.7; p = 0.142). Levels of GI.1 and GII.4 HBGA-blocking antibodies were increased in vaccinees and in some placebo AGE cases infected with GII.2, indicating cross-reactivity in the immune responses to different genotypes. INTERPRETATION: Despite limited cases of homotypic norovirus AGE meaning the primary endpoint was not fully evaluable, we showed TAK-214 provided statistically significant efficacy against "any moderate/severe norovirus AGE" principally caused by the heterotypic GII.2 genotype, demonstrating induction of cross-genotype protection.

Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel.

OBJECTIVES: To compare rates of myopericarditis, severe and serious dermatological or neurological events, and other adverse events in deploying US military personnel who received or did not receive ACAM2000® (Smallpox [Vaccinia] Vaccine, Live) vaccine and to evaluate potential risk factors for development of myopericarditis. METHODS: Prospective observational cohort study enrolling up to 15,000 ACAM2000 recipients (Cohort 1) and up to 5000 persons otherwise eligible for ACAM2000 vaccination but not vaccinated due to recency of vaccination or characteristics of their contacts (Cohort 2). Data and specimens were collected initially and 10 (6-17) days later. Those with clinical or laboratory evidence of possible myopericarditis were referred for further evaluation and adjudication by a blinded independent review committee. The adjusted odds ratio for myopericarditis was determined by a logistic regression model controlling for age, race, gender, and exercise regimen. RESULTS: 14,667 subjects provided initial data and specimens (Cohort 1, 10,825; Cohort 2, 3842); 12,110 (Cohort 1, 8945; Cohort 2, 3165) completed Visit 2 per-protocol. A total of 125 (Cohort 1, 111; Cohort 2, 14) were referred for myopericarditis adjudication, yielding 54 (Cohort 1, 44, Cohort 2, 10) subclinical myopericarditis, 5 suspected myocarditis, 1 confirmed myocarditis, and 1 suspected pericarditis. Unadjusted myopericarditis rates were: Cohort 1, 5.7/1000 (95% CI, 4.3-7.5); Cohort 2, 3.2/1000 (95% CI, 1.7-5.8). Unadjusted and adjusted odds ratios for myopericarditis were 1.8 (95% CI: 0.9-3.6) and 1.3 (95% CI: 0.6-2.6), respectively. One hundred seventeen subjects (1.1%) in Cohort 1 and 13 (0.3%) in Cohort 2 experienced at least 1 serious adverse event. No instances of serious and severe neurological or dermatological adverse events were reported. CONCLUSIONS: In this carefully screened, generally young and healthy service-member population, ACAM2000 vaccination was associated with modest non-significant increases in the risk of myopericarditis (adjusted OR, 1.3; unadjusted OR, 1.8); all but seven cases were subclinical. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT00928577.

Mental health, physical health, and health-related behaviors of U.S. Army Special Forces.

OBJECTIVES: To prospectively examine the health and health-related behaviors of Army Special Forces personnel in comparison with two distinct, but functionally similar Army groups. METHODS: Special Forces, Ranger Qualified, and General Purposes Forces enrolled in the Millennium Cohort Study were identified using data from the Defense Manpower Data Center. Using prospective survey data (2001-2014), we estimated the association of Army specialization with mental health, social support, physical health, and health-related behaviors with multivariable regression models. RESULTS: Among the 5,392 eligible participants (84.4% General Purposes Forces, 10.0% Special Forces, 5.6% Ranger Qualified), Special Forces personnel reported the lowest prevalence of mental disorders, physical health problems, and unhealthy behaviors. In the multivariable models, Special Forces personnel were less likely to report mental health problems, multiple somatic symptoms, and unhealthy behaviors compared with General Purpose Forces infantrymen (odds ratios [OR]: 0.20-0.54, p-values < .01). Overall, Special Forces personnel were similar in terms of mental and physical health compared with Ranger Qualified infantrymen, but were less likely to sleep < 5 hours/night (OR: 0.60, 95% confidence intervals: 0.40, 0.92) and have 5 or more multiple somatic symptoms (OR: 0.69, 95% CI: 0.49, 0.98). Both Special Forces personnel and Ranger Qualified infantrymen engaged in more healthy behaviors compared with General Purpose Forces infantrymen (OR: 2.57-6.22, p-values<0.05). Engagement in more healthy behaviors reduced the odds of subsequent adverse health outcomes, regardless of specialization. CONCLUSIONS: Army Special Forces personnel were found to be mentally and physically healthier than General Purpose Forces infantrymen, which may in part be due to their tendency to engage in healthy behaviors. Findings indicate that engagement in a greater number of healthy behaviors may reduce odds for subsequent adverse outcomes.

Postpartum Fitness and Body Mass Index Changes in Active Duty Navy Women.

INTRODUCTION: Active duty Navy women participate in biannual Physical Fitness Assessments (PFAs), which include height and weight measurements and a Physical Readiness Test (PRT). PFAs are waived during pregnancy and resume the cycle after 6 months following maternity leave. The purpose of this study was to compare changes in PFA results over time between women who had or did not have a live birth during the follow-up period, and identify characteristics of women with lower PFA results postpartum. MATERIALS AND METHODS: This longitudinal study included 14,142 active duty Navy women, aged 19-40 years, with PFA results during July 2011-June 2015. Multivariable logistic regression, Stuart-Maxwell tests, and mixed effects modeling were used to examine changes in PRT scores and body mass index over time between women with and without a live birth during follow-up. All data were analyzed in 2017. This study was approved by the institutional review boards at the Uniformed Services University Office of Research and the Naval Health Research Center, and informed consent was waived in accordance with 32 CFR § 219.116(d). RESULTS: Postpartum women had increased odds of PRT failures (AOR = 3.88, 95% CI: 1.44-10.40) and lower PRT scores (AOR = 1.47, 95% CI: 1.12-1.92) up to 2.5 years postpartum, versus women without a live birth. Being enlisted, obese/overweight prepregnancy, and younger were risk factors for suboptimal PFA outcomes. Mean core strength and cardiovascular endurance, but not upper body strength, scores were significantly lower in postpartum women at 1 year postpartum versus women without a live birth. CONCLUSIONS: Our findings show that additional interventions may be needed to assist women in returning to prepregnancy fitness up to 1 year postpartum. Future studies should examine additional factors that may improve postpartum fitness in addition to enhancing maternity leave policies.

Seasonal Influenza Vaccine Impact on Pandemic H1N1 Vaccine Efficacy.

BACKGROUND: In 2009, a novel influenza A (pH1N1) was identified, resulting in a pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was separately produced in addition to the seasonal trivalent influenza vaccine. Formulation of the seasonal influenza vaccine (injectable trivalent inactivated influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV]) was postulated to have impacted the efficacy of the pH1N1 vaccination. METHODS: We reviewed electronic health and databases, which included vaccination records, and healthcare encounters for influenza-like illness (ILI), influenza, and pneumonia among US military members. We examined rates by vaccination type to identify factors associated with the risk for study outcomes. RESULTS: Compared with those receiving the seasonal influenza vaccine alone, subjects receiving the pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and 0.35, respectively). There was no clinically significant difference in ILI, influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with or without presence of the seasonal vaccine. Similarly, there was no clinically relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV recipients. CONCLUSIONS: During the 2009-2010 pandemic, the pH1N1 vaccination was effective in reducing rates of ILI, influenza, and pneumonia. Administration of the seasonal vaccine should continue without concern of potential interference with a novel pandemic vaccine, though more studies are needed to determine if this is applicable to other influenza seasons.

New-Onset Asthma and Combat Deployment: Findings From the Millennium Cohort Study.

Recent reports suggest US military service members who deployed in support of the recent conflicts in Iraq and Afghanistan have higher rates of new-onset asthma than those who did not deploy. However, it is unknown whether combat experiences, in addition to deployment, contribute to new-onset asthma risk. This study aimed to longitudinally determine the risk factors for developing asthma, including combat deployment (categorized as deployed with combat experience, deployed without combat experience, or nondeployed), among participants in the Millennium Cohort Study from 2001 to 2013. A total of 75,770 participants completed a baseline survey and at least 1 triennial follow-up survey on deployment experiences, lifestyle characteristics, and health outcomes. Complementary log-log models stratified by sex were used to estimate the relative risk of developing asthma among participants who reported no history of asthma at baseline. In models with adjustments, those who deployed with combat experience were 24%-30% more likely to develop asthma than those who did not deploy. Deployed personnel without combat experience were not at a higher risk for new-onset asthma compared with nondeployers. Further research is needed to identify specific features of combat that are associated with greater asthma risk to inform prevention strategies.

Measuring Aggregated and Specific Combat Exposures: Associations Between Combat Exposure Measures and Posttraumatic Stress Disorder, Depression, and Alcohol-Related Problems.

Research has shown combat exposure to be associated with negative mental health outcomes. Different combat exposure measures are not composed of the same combat experiences, and few combat exposure measures have been directly compared to another measure. Furthermore, research about the unique associations between specific combat experiences and mental health is lacking. We investigated associations between new-onset posttraumatic stress disorder (PTSD), new-onset depression, and alcohol-related problems and two commonly used measures of combat among a sample of 20,719 recently deployed U.S. military personnel. A 13-item measure assessed both direct and indirect combat exposures, and a 5-item measure assessed only indirect exposures. Both combat measures were associated with all outcomes in the same direction (e.g., PTSD, odds ratio [OR] = 2.97 vs. 4.01; depression, OR = 2.03 vs. 2.42; alcohol-related problems, OR = 1.41 vs. 1.62, respectively, for the 5- and 13-item measures). The 13-item measure had a stronger association with some outcomes, particularly PTSD. Each specific item had significant bivariate associations with all outcomes, ORs = 1.43-4.92. After adjusting for other combat exposures, items assessing witnessing abuse, feeling in danger, and knowing someone injured or killed remained associated with all outcomes, ORs = 1.18-2.72. After this adjustment, several items had unexpected protective associations with some mental health outcomes. Results indicated these two combat exposure measures were approximately equally effective for determining risk for negative mental health outcomes in a deployed population, despite having different content. Additional research is needed to replicate and understand how specific combat exposures affect health.

Department of Defense Birth and Infant Health Registry: select reproductive health outcomes, 2003-2014.

Established following a 1998 directive, the Department of Defense Birth and Infant Health Registry (Registry) team conducts surveillance of select reproductive health outcomes among military families. Data are compiled from the Military Health System Data Repository and Defense Manpower Data Center to define the Registry cohort and outcomes of interest. Outcomes are defined using ICD-9/ICD-10 and Current Procedural Terminology codes, and include: pregnancy outcomes (e.g., live births, losses), birth defects, preterm births, and male:female infant sex ratio. This report includes data from 2003-2014 on 1,304,406 infants among military families and 258,332 pregnancies among active duty women. Rates of common adverse infant and pregnancy outcomes were comparable to or lower than those in the general US population. These observations, along with prior Registry analyses, provide reassurance that military service is not independently associated with increased risks for select adverse reproductive health outcomes. The Registry's diverse research portfolio demonstrates its unique capabilities to answer a wide range of questions related to reproductive health. These data provide the military community with information to identify successes and areas for improvement in prevention and care.

Immune Responses in U.S. Military Personnel Who Received Meningococcal Conjugate Vaccine (MenACWY) Concomitantly with Other Vaccines Were Higher than in Personnel Who Received MenACWY Alone.

Immunological responses to vaccination can differ depending on whether the vaccine is given alone or with other vaccines. This study was a retrospective evaluation of the immunogenicity of a tetravalent meningococcal conjugate vaccine for serogroups A, C, W, and Y (MenACWY) administered alone (n = 41) or concomitantly with other vaccines (n = 279) to U.S. military personnel (mean age, 21.6 years) entering the military between 2006 and 2008. Concomitant vaccines included tetanus/diphtheria (Td), inactivated polio vaccine (IPV), hepatitis vaccines, and various influenza vaccines, among others; two vaccine groups excluded Tdap and IPV. Immune responses were evaluated in baseline and postvaccination sera for Neisseria meningitidis serogroups C and Y 1 to 12 months (mean, 4.96 months) following vaccination. Functional antibodies were measured by using a serum bactericidal antibody assay with rabbit complement (rSBA) and by measurement of serogroup-specific immunoglobulin G (IgG) antibodies. The percentage of vaccinees reaching threshold levels (IgG concentration in serum, ≥2 µg/ml; rSBA titer, ≥8) corresponding to an immunologic response was higher postvaccination than at baseline (P < 0.001). Administration of MenACWY along with other vaccines was associated with higher geometric means of IgG concentrations and rSBA titers than those measured 4.60 months after a single dose of MenACWY. In addition, higher percentages of vaccinees reached the immunological threshold (range of odds ratios [ORs], 1.5 to 21.7) and more of them seroconverted (OR range, 1.8 to 4.8) when MenACWY was administered with any other vaccine than when administered alone. Additional prospective randomized clinical trials are needed to confirm the observed differences among groups in the immune response to MenACWY when given concomitantly with other vaccines to U.S. military personnel.

Effect of multiple, simultaneous vaccines on polio seroresponse and associated health outcomes.

BACKGROUND: Administration of multiple simultaneous vaccines to infants, children, and military recruits is not uncommon. However, little research exists to examine associated serological and health effects, especially in adults. METHOD: We retrospectively examined 416 paired serum specimens from U.S. military subjects who had received the inactivated polio vaccine (IPV) alone or in combination with either 1 other vaccine (<3 group) or 4 other vaccines (>4 group). Each of the 2 groups was subdivided into 2 subgroups in which Tdap was present or absent. RESULTS: The >4 group was associated with a higher proportion of polio seroconversions than the <3 group (95% vs. 58%, respectively, p<0.01). Analysis of the <3 subgroup that excluded Tdap vs. the >4 subgroup that excluded Tdap showed no difference between them (p>0.1). However, the >4 subgroup that included Tdap had significantly more seroconversions than either the <3 subgroup that excluded Tdap or the >4 subgroup that excluded Tdap (p<0.01). Overall, at least 98% of subjects were at or above the putative level of seroprotection both pre- and post-vaccination, yet at least 81% of subjects seroconverted. In an analysis of 400 of the subjects in which clinic in- and outpatient encounters were counted over the course of 1 year following vaccinations, there was no significant difference between the 2 groups (p>0.1). CONCLUSION: A combination of >4 vaccines including IPV appeared to have an immunopotentiation effect on polio seroconversion, and Tdap in particular was a strong candidate for an important role. The dose of IPV we studied in our subjects, who already had a high level of seroprotection, acted as a booster. In addition, there appear to be no negative health consequences from receiving few versus more multiple simultaneous vaccinations.

Retrospective analysis of demographic and clinical factors associated with etiology of febrile respiratory illness among US military basic trainees.

BACKGROUND: Basic trainees in the US military have historically been vulnerable to respiratory infections. Adenovirus and influenza are the most common etiological agents responsible for febrile respiratory illness (FRI) among trainees and present with similar clinical signs and symptoms. Identifying demographic and clinical factors associated with the primary viral pathogens causing FRI epidemics among trainees will help improve differential diagnosis and allow for appropriate distribution of antiviral medications. The objective of this study was to determine what demographic and clinical factors are associated with influenza and adenovirus among military trainees. METHODS: Specimens were systematically collected from military trainees meeting FRI case definition (fever ≥38.0°C with either cough or sore throat; or provider-diagnosed pneumonia) at eight basic training centers in the USA. PCR and/or cell culture testing for respiratory pathogens were performed on specimens. Interviewer-administered questionnaires collected information on patient demographic and clinical factors. Polychotomous logistic regression was employed to assess the association between these factors and FRI outcome categories: laboratory-confirmed adenovirus, influenza, or other FRI. Sensitivity, specificity, positive and negative predictive value were calculated for individual predictors and clinical combinations of predictors. RESULTS: Among 21,570 FRI cases sampled between 2004 and 2009, 63.6% were laboratory-confirmed adenovirus cases and 6.6% were laboratory-confirmed influenza cases. Subjects were predominantly young men (86.8% men; mean age 20.8 ± 3.8 years) from Fort Jackson (18.8%), Great Lakes (17.1%), Fort Leonard Wood (16.3%), Marine Corps Recruit Depot (MCRD) San Diego (19.0%), Fort Benning (13.3%), Lackland (7.5%), MCRD Parris Island (8.7%), and Cape May (3.2%). The best multivariate predictors of adenovirus were the combination of sore throat (odds ratio [OR], 2.94; 95% confidence interval [CI], 2.66-3.25), cough (OR, 2.33; 95% CI, 2.11-2.57), and fever (OR, 2.07; 95% CI, 1.90-2.26) with a PPV of 77% (p ≤ .05). A combination of cough, fever, training week 0-2 and acute onset were most predictive of influenza (PPV =38%; p ≤ .05). CONCLUSIONS: Specific demographic and clinical factors were associated with laboratory-confirmed influenza and adenovirus among military trainees. Findings from this study can guide clinicians in the diagnosis and treatment of military trainees presenting with FRI.