Trichomonas vaginalis infection and prostate-specific antigen concentration: Insights into prostate involvement and prostate disease risk.

BACKGROUND: The protist Trichomonas vaginalis causes a common, sexually transmitted infection and has been proposed to contribute to the development of chronic prostate conditions, including benign prostatic hyperplasia and prostate cancer. However, few studies have investigated the extent to which it involves the prostate in the current antimicrobial era. We addressed this question by investigating the relation between T. vaginalis antibody serostatus and serum prostate-specific antigen (PSA) concentration, a marker of prostate infection, inflammation, and/or cell damage, in young, male, US military members. METHODS: We measured T. vaginalis serum IgG antibodies and serum total PSA concentration in a random sample of 732 young, male US active duty military members. Associations between T. vaginalis serostatus and PSA were investigated by linear regression. RESULTS: Of the 732 participants, 341 (46.6%) had a low T. vaginalis seropositive score and 198 (27.0%) had a high score, with the remainder seronegative. No significant differences were observed in the distribution of PSA by T. vaginalis serostatus. However, slightly greater, nonsignificant differences were observed when men with high T. vaginalis seropositive scores were compared with seronegative men, and when higher PSA concentrations were examined (≥0.70 ng/mL). Specifically, 42.5% of men with high seropositive scores had a PSA concentration greater than or equal to 0.70 ng/mL compared with 33.2% of seronegative men (adjusted P = .125). CONCLUSIONS: Overall, our findings do not provide strong support for prostate involvement during T. vaginalis infection, although our suggestive positive findings for higher PSA concentrations do not rule out this possibility entirely. These suggestive findings may be relevant for prostate condition development because higher early- to mid-life PSA concentrations have been found to predict greater prostate cancer risk later in life.

Sustained influence of infections on prostate-specific antigen concentration: An analysis of changes over 10 years of follow-up.

BACKGROUND: To extend our previous observation of a short-term rise in prostate-specific antigen (PSA) concentration, a marker of prostate inflammation and cell damage, during and immediately following sexually transmitted and systemic infections, we examined the longer-term influence of these infections, both individually and cumulatively, on PSA over a mean of 10 years of follow-up in young active duty U.S. servicemen. METHODS: We measured PSA in serum specimens collected in 1995-7 (baseline) and 2004-6 (follow-up) from 265 men diagnosed with chlamydia (CT), 72 with gonorrhea (GC), 37 with non-chlamydial, non-gonococcal urethritis (NCNGU), 58 with infectious mononucleosis (IM), 91 with other systemic or non-genitourinary infections such as varicella; and 125-258 men with no infectious disease diagnoses in their medical record during follow-up (controls). We examined the influence of these infections on PSA change between baseline and follow-up. RESULTS: The proportion of men with any increase in PSA (>0 ng/mL) over the 10-year average follow-up was significantly higher in men with histories of sexually transmitted infections (CT, GC, and NCNGU; 67.7% vs 60.8%, P = 0.043), systemic infections (66.7% vs 54.4%, P = 0.047), or any infections (all cases combined; 68.5% vs 54.4%, P = 0.003) in their military medical record compared to controls. CONCLUSIONS: While PSA has been previously shown to rise during acute infection, these findings demonstrate that PSA remains elevated over a longer period. Additionally, the overall infection burden, rather than solely genitourinary-specific infection burden, contributed to these long-term changes, possibly implying a role for the cumulative burden of infections in prostate cancer risk.

Insight into infection-mediated prostate damage: Contrasting patterns of C-reactive protein and prostate-specific antigen levels during infection.

BACKGROUND: To investigate mechanisms underlying our previous observation of a large rise in serum prostate-specific antigen, a marker of prostate pathology, during both sexually transmitted and systemic infections, we measured serum high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, in our previous case-control study of young, male US military members and compared our findings to those for PSA. METHODS: We measured hsCRP before and during infection for 299 chlamydia, 112 gonorrhea, and 59 non-chlamydial, non-gonococcal urethritis (NCNGU) cases; before and after infection for 55 infectious mononucleosis (IM) and 90 other systemic/non-genitourinary cases; and for 220-256 controls. RESULTS: Only gonorrhea cases were significantly more likely to have a large hsCRP rise (≥1.40 mg/L or ≥239%) during infection than controls (P < 0.01). However, gonorrhea, IM, and other systemic/non-genitourinary cases were more likely to have a rise of any magnitude up to one year post-diagnosis than controls (p = 0.038-0.077). CONCLUSIONS: These findings, which differ from those for PSA, suggest distinct mechanisms of elevation for hsCRP and PSA, and support both direct (eg, prostate infection) and indirect (eg, systemic inflammation-mediated prostate cell damage) mechanisms for PSA elevation. Future studies should explore our PSA findings further for their relevance to both prostate cancer screening and risk.

Stellate Ganglion Block in the Treatment of Post-traumatic Stress Disorder: A Review of Historical and Recent Literature.

Concerns over the rising prevalence of post-traumatic stress disorder (PTSD), particularly among military service members returning from combat, and over barriers that hinder individuals from seeking out or adhering to standard therapies have contributed to interest in alternative therapies for the disorder. A novel alternative therapy for PTSD-stellate ganglion block (SGB)-may be considered lacking in formal evidence of efficacy despite having shown considerable promise. This review of the recent and historical literature related to SGB finds evidence of substantial beneficial psychiatric effects and substantiates that this fast-acting, somatic treatment may provide positive results for patients with PTSD and may reduce barriers to therapy, particularly among military populations.

Infectious mononucleosis, other infections and prostate-specific antigen concentration as a marker of prostate involvement during infection.

Although Epstein-Barr virus has been detected in prostate tissue, no associations have been observed with prostate cancer in the few studies conducted to date. One possible reason for these null findings may be use of cumulative exposure measures that do not inform the timing of infection, i.e., childhood versus adolescence/early adulthood when infection is more likely to manifest as infectious mononucleosis (IM). We sought to determine the influence of young adult-onset IM on the prostate by measuring prostate-specific antigen (PSA) as a marker of prostate inflammation/damage among U.S. military members. We defined IM cases as men diagnosed with IM from 1998 to 2003 (n = 55) and controls as men without an IM diagnosis (n = 255). We selected two archived serum specimens for each participant, the first collected after diagnosis for cases and one randomly selected from 1998 to 2003 for controls (index), as well as the preceding specimen (preindex). PSA was measured in each specimen. To explore the specificity of our findings for prostate as opposed to systemic inflammation, we performed a post hoc comparison of other infectious disease cases without genitourinary involvement (n = 90) and controls (n = 220). We found that IM cases were more likely to have a large PSA rise than controls (≥ 20 ng/mL: 19.7% versus 8.8%, p = 0.027; ≥ 40% rise: 25.7% versus 9.4%, p = 0.0021), as were other infectious disease cases (25.7% versus 14.0%, p = 0.020; 27.7% versus 18.0%, p = 0.092). These findings suggest that, in addition to rising because of prostate infection, PSA may also rise because of systemic inflammation, which could have implications for PSA interpretation in older men.

Psychiatric effects of malaria and anti-malarial drugs: historical and modern perspectives.

The modern medical literature implicates malaria, and particularly the potentially fatal form of cerebral malaria, with a risk of neurocognitive impairment. Yet historically, even milder forms of malaria were associated in the literature with a broad range of psychiatric effects, including disorders of personality, mood, memory, attention, thought, and behaviour. In this article, the history of psychiatric effects attributed to malaria and post-malaria syndromes is reviewed, and insights from the historical practice of malariotherapy in contributing to understanding of these effects are considered. This review concludes with a discussion of the potentially confounding role of the adverse effects of anti-malarial drugs, particularly of the quinoline class, in the unique attribution of certain psychiatric effects to malaria, and of the need for a critical reevaluation of the literature in light of emerging evidence of the chronic nature of these adverse drug effects.

The timeliness of the US military response to the 2014 Ebola disaster: a critical review.

In the face of an unprecedented epidemic of Ebola Virus Disease, in September 2014, the US military began sending thousands of personnel to Liberia and supporting areas in Senegal in its largest deployment to the African continent in over two decades. In this review, media reports, published photographs and official statements are evaluated and summarized to identify and describe key time points in the US military response. Specific events include the initial establishment of the Monrovia Medical Unit and the buildup of forces for the expanded mission, which involved enhancement of laboratory testing capacity, construction of Ebola Treatment Units, and training of health care workers. The review concludes with a discussion and critical evaluation of the timeliness of this US military response in the context of the original expectations of the humanitarian community and government officials.

Population estimates of undocumented incident traumatic brain injuries among combat-deployed US military personnel.

OBJECTIVE: To estimate the number of undocumented incident traumatic brain injuries (TBIs) among active component US military personnel serving in Iraq and Afghanistan prior to policy changes implemented in late 2006 and 2010 that improved TBI documentation. METHODS: Negative binomial regression was used to model monthly incident TBI counts between December 2010 and June 2012 (N = 19) and then estimate expected monthly counts of incident TBIs during 2 periods: January 2003-October 2006 and November 2006-November 2010. Monthly amputation counts from Department of Defense surveillance data were used as a proxy for changing injury rates. Monthly active component deployment estimates derived from the Congressional Research Service, Brookings Institution, and Defense Manpower Data Center were used to estimate the size of the at-risk population each month. The difference between expected monthly incident TBI counts and reported counts is presented as the estimated number of undocumented incident TBIs. RESULTS: The full model estimates that 21 257 active component military personnel experienced undocumented incident TBIs while deployed in Iraq or Afghanistan between January 2003 and October 2006, more than 4 times the 5272 incident TBIs documented during that period. CONCLUSIONS: A sizeable majority of Iraq and Afghanistan combat veterans who experienced incident TBI while deployed prior to November 2006 are likely to have had their injuries undocumented, creating challenges for clinical care, disability evaluation, and future research.

Mass administration of the antimalarial drug mefloquine to Guantánamo detainees: a critical analysis.

Recently, evidence has emerged from an unusual form of mass drug administration practised among detainees held at US Naval Station Guantánamo Bay, Cuba ('Guantánamo'), ostensibly as a public health measure. Mefloquine, an antimalarial drug originally developed by the US military, whose use is associated with a range of severe neuropsychiatric adverse effects, was administered at treatment doses to detainees immediately upon their arrival at Guantánamo, prior to laboratory testing for malaria and irrespective of symptoms of disease. In this analysis, the history of mefloquine's development is reviewed and the indications for its administration at treatment doses are discussed. The stated rationale for the use of mefloquine among Guantánamo detainees is then evaluated in the context of accepted forms of population-based malaria control. It is concluded that there was no plausible public health indication for the use of mefloquine at Guantánamo and that based on prevailing standards of care, the clinical indications for its use are decidedly unclear. This analysis suggests the troubling possibility that the use of mefloquine at Guantánamo may have been motivated in part by knowledge of the drug's adverse effects, and points to a critical need for further investigation to resolve unanswered questions regarding the drug's potentially inappropriate use.

Prostate-specific antigen concentration in young men: new estimates and review of the literature.

UNLABELLED: Study Type--Diagnostic (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Although non-recommended PSA testing has been reported in men younger than 40 years of age, there are few recognized data on PSA in younger American men, particularly younger African-American men, to provide age- and race-specific references. Using data from an existing large study of young, male members of the US military, aged 28-36 years, the present study provides PSA reference distributions for young Caucasian-American men (median = 0.56, 95th percentile = 1.42, range: <0.01-3.34 ng/mL) and African-American men (median = 0.64, 95th percentile = 1.89, range: 0.12-6.45 ng/mL). Previous estimates from the literature are also summarized. OBJECTIVE: • To provide race-specific prostate-specific antigen (PSA) reference distributions for young men less than 40 years of age who might have undergone non-recommended PSA testing because of their family history of prostate cancer or inadvertently as part of a standard panel of tests. MATERIALS AND METHODS: • We used data from a large existing study of young, male Caucasian- and African-American members of the US military with stored serum in the Department of Defense serum repository. • As part of this previous study, we selected a random sample of 373 Caucasian- and 366 African-American men aged 28-36 years with an archived serum specimen collected for standard military purposes from 2004 to 2006. • We measured serum total PSA concentration in this specimen using the Beckman Coulter Access Hybritech PSA assay. RESULTS: • The PSA level ranged from <0.01 to 3.34 ng/mL among Caucasian-American men, with a median of 0.56 ng/mL and a 95th percentile of 1.42 ng/mL. • The PSA level ranged from 0.12 to 6.45 ng/mL among African-American men, with a median of 0.64 ng/mL and 95th percentile of 1.89 ng/mL. • The PSA level was significantly higher in African- than in Caucasian-American men (P= 0.001). CONCLUSION: • The PSA estimates, together with those summarized from the literature, provide age- and race-specific PSA reference distributions for young men who might have undergone non-recommended PSA testing. • Comparisons by race could also begin to inform the timing of divergence of prostate cancer risk by race.

Mefloquine prescriptions in the presence of contraindications: prevalence among US military personnel deployed to Afghanistan, 2007.

PURPOSE: Contraindications to mefloquine use include a history of certain prevalent neuropsychiatric disorders, which are thought to increase the risk of severe adverse events including anxiety, paranoia, depression, hallucinations, psychosis, and possibly suicide. Within the US military, the continued availability and use of mefloquine is subject to administrative policies dating to 2002 that require clinicians to exercise added caution during prescribing. This analysis was performed to quantify the effectiveness of these policies in ensuring health care provider compliance with package insert prescribing guidance. METHODS: A previously identified cohort consisting of 11,725 active duty US military personnel, among whom 1127 (9.6%) had contraindications to mefloquine use identified through medical surveillance and pharmaceutical databases, was examined to identify individuals receiving prescriptions for mefloquine in the 45 days prior to a combat deployment in 2007. RESULTS: Among the 11,725 cohort members, 4505 (38.4% of the cohort) received a prescription for mefloquine. Among the 1127 cohort members with contraindications, 155 (1.3% of the cohort) were prescribed mefloquine, comprising 13.8% of those with contraindications. CONCLUSIONS: Despite the longstanding administrative policies meant to reduce such events, approximately one in seven individuals with neuropsychiatric contraindications received a prescription for mefloquine prior to a recent combat deployment, significantly increasing the risk of subsequent adverse events. Given the prevalence of neuropsychiatric disorders among US military personnel and the continued availability of mefloquine, additional study is recommended to describe and quantify the nature and extent of mefloquine-associated adverse events experienced among this group.

Epileptogenic potential of mefloquine chemoprophylaxis: a pathogenic hypothesis.

BACKGROUND: Mefloquine has historically been considered safe and well-tolerated for long-term malaria chemoprophylaxis, but prescribing it requires careful attention in order to rule out contraindications to its use. Contraindications include a history of certain neurological conditions that might increase the risk of seizure and other adverse events. The precise pathophysiological mechanism by which mefloquine might predispose those with such a history to seizure remains unclear. PRESENTATION OF THE HYPOTHESIS: Studies have demonstrated that mefloquine at doses consistent with chemoprophylaxis accumulates at high levels in brain tissue, which results in altered neuronal calcium homeostasis, altered gap-junction functioning, and contributes to neuronal cell death. This paper reviews the scientific evidence associating mefloquine with alterations in neuronal function, and it suggests the novel hypothesis that among those with the prevalent EPM1 mutation, inherited and mefloquine-induced impairments in neuronal physiologic safeguards might increase risk of GABAergic seizure during mefloquine chemoprophylaxis. TESTING AND IMPLICATIONS OF THE HYPOTHESIS: Consistent with case reports of tonic-clonic seizures occurring during mefloquine chemoprophylaxis among those with family histories of epilepsy, it is proposed here that a new contraindication to mefloquine use be recognized for people with EPM1 mutation and for those with a personal history of myoclonus or ataxia, or a family history of degenerative neurologic disorder consistent with EPM1. Recommendations and directions for future research are presented.

Low validity of self-report in identifying recent mental health diagnosis among U.S. service members completing Pre-Deployment Health Assessment (PreDHA) and deployed to Afghanistan, 2007: a retrospective cohort study.

BACKGROUND: Since 1998, the U.S. Armed Forces has used the mandatory Pre-Deployment Health Assessment (PreDHA) screening questionnaire as a means of assessing the health and suitability of U.S. service members for deployment. Limited data exists to quantify the validity of the self-reported PreDHA. This study was conducted to assess the validity of self-reporting in PreDHA to identify deployed service members who have had a recent mental health disorder diagnosis. METHODS: A retrospective cohort study was conducted on 15,195 U.S. service members deployed in support of combat and reconstruction operations in Afghanistan. The Defense Medical Surveillance System (DMSS), the DoD's longitudinal medical surveillance database, was queried to identify cases among the cohort with a recent diagnosis of a pertinent mental health disorder and to obtain those subjects' responses to the PreDHA. RESULTS: Of the study cohort, 11,179 (73.6%) subjects had a PreDHA available within the DMSS at the time of analysis. A total of 615 subjects (4.0%) had one or more mental health disorder diagnoses during the pre-deployment period. Out the 615 subjects with diagnosed mental health disorders, 465 had a PreDHA. Among these, only 224, not quite half, answered in the affirmative to the PreDHA question: "During the past year, have you sought counseling or care for your mental health?" CONCLUSION: This study demonstrates that the self-reported PreDHA has low validity for identifying service members with diagnosed mental health disorders. The development of electronic decision-support systems which automatically screen electronic health records to identify high-risk service members may prove a valuable component of improved pre-deployment screening processes.

Pain and discomfort in deployed helicopter aviators wearing body armor.

BACKGROUND: In early 2007, U.S. Army helicopter aviators deployed to Afghanistan complained of increased pain frequency during flight. The aviators attributed this pain to body armor, which had not been worn prior to deployment. This study was conducted to investigate these complaints. METHODS: A retrospective study of pain frequency among 68 deployed helicopter aviators was performed using self-reported categorical pain ratings and flight times abstracted from a safety questionnaire. To assess the association of substantial increases in flight time on reported pain frequency, study subjects were divided into a group reporting a decrease or increase of 1 h or less in average daily flight hours during deployment as compared to predeployment (level flight hours, LFH) and a group reporting an increase of greater than 1 h in average daily flight hours (increased flight hours, IFH). RESULTS: A significantly higher proportion of aviators in the IFH group reported an increase in pain frequency as compared to LFH (81.5% vs. 61.1%, respectively). The relative risk (RR) of increased pain frequency associated with IFH was greatest in the lower back (RR = 1.80), legs (RR = 2.60), arms (RR = 9.11), and the groin (RR = 12.1). DISCUSSION: This study provides preliminary evidence that complaints of increased pain frequency during deployment were associated with substantial increases in flight times. Further study is warranted to investigate and confirm the underlying causes of this pain.