Hepatitis B seroprevalence in the U.S. military and its impact on potential screening strategies.

INTRODUCTION: Knowledge of the contemporary epidemiology of hepatitis B virus (HBV) infection among military personnel can inform potential Department of Defense (DoD) screening policy and infection and disease control strategies. MATERIALS AND METHODS: HBV infection status at accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period from 2007 to 2010. A cost model was developed from the perspective of the Department of Defense for a program to integrate HBV infection screening of applicants for military service into the existing screening program of screening new accessions for vaccine-preventable infections. RESULTS: The prevalence of chronic HBV infection at accession was 2.3/1,000 (95% CI: 1.4, 3.2); most cases (16/21, 76%) identified after deployment were present at accession. There were 110 military service-related HBV infections identified. Screening accessions who are identified as HBV susceptible with HBV surface antigen followed by HBV surface antigen neutralization for confirmation offered no cost advantage over not screening and resulted in a net annual increase in cost of $5.78 million. However, screening would exclude as many as 514 HBV cases each year from accession. CONCLUSIONS: Screening for HBV infection at service entry would potentially reduce chronic HBV infection in the force, decrease the threat of transfusion-transmitted HBV infection in the battlefield blood supply, and lead to earlier diagnosis and linkage to care; however, applicant screening is not cost saving. Service-related incident infections indicate a durable threat, the need for improved laboratory-based surveillance tools, and mandate review of immunization policy and practice.

Use of quadrivalent human papillomavirus vaccine and the prevalence of antibodies to vaccine-targeted strains among female service members before and after vaccination.

The quadrivalent human papillomavirus vaccine (HPV4) has been shown to generate a robust immune response among fully vaccinated individuals; however, among U.S. service members, HPV vaccine completion rates are low. This study compared the immunogenicity of HPV4 vaccine among partially and fully vaccinated service members at 4-6 years post-vaccination. A random sample was obtained of 2,091 female service members, aged 17-26 years, who received 1-3 HPV4 doses during 2006-2012, stratified by number of doses (one, two, or three). Pre- and post-immunization sera from these service members were tested for antibodies to the HPV strains covered by the vaccine. Prior to immunization 42% were seropositive for HPV strain 6; 34% for strain 11; 29% for strain 16; and 16% for strain 18. Among those naive to all four strains prior to immunization, there was 100% seroconversion after one, two, or three doses. The results indicate that many service members had already been exposed to strains of HPV prior to receiving the vaccine; however, seropositivity prevalence was lower for the oncogenic HPV strains 16 and 18. The data demonstrate sustained immunogenicity after a single dose of vaccine, with modest improvement with successive doses for all strains except 18.

Costs and consequences: Hepatitis C seroprevalence in the military and its impact on potential screening strategies.

UNLABELLED: Knowledge of the contemporary epidemiology of hepatitis C viral (HCV) infection among military personnel can inform potential Department of Defense screening policy. HCV infection status at the time of accession and following deployment was determined by evaluating reposed serum from 10,000 service members recently deployed to combat operations in Iraq and Afghanistan in the period 2007-2010. A cost model was developed from the perspective of the Department of Defense for a military applicant screening program. Return on investment was based on comparison between screening program costs and potential treatment costs avoided. The prevalence of HCV antibody-positive and chronic HCV infection at accession among younger recently deployed military personnel born after 1965 was 0.98/1000 (95% confidence interval 0.45-1.85) and 0.43/1000 (95% confidence interval 0.12-1.11), respectively. Among these, service-related incidence was low; 64% of infections were present at the time of accession. With no screening, the cost to the Department of Defense of treating the estimated 93 cases of chronic HCV cases from a single year's accession cohort was $9.3 million. Screening with the HCV antibody test followed by the nucleic acid test for confirmation yielded a net annual savings and a $3.1 million dollar advantage over not screening. CONCLUSIONS: Applicant screening will reduce chronic HCV infection in the force, result in a small system costs savings, and decrease the threat of transfusion-transmitted HCV infection in the battlefield blood supply and may lead to earlier diagnosis and linkage to care; initiation of an applicant screening program will require ongoing evaluation that considers changes in the treatment cost and practice landscape, screening options, and the epidemiology of HCV in the applicant/accession and overall force populations.

Incidence of genital warts among U.S. service members before and after the introduction of the quadrivalent human papillomavirus vaccine.

Human papillomavirus (HPV) is the most common sexually transmitted infection among U.S. military members. The most frequent clinical manifestation of HPV is genital warts (GW). This investigation examined the annual incidence of diagnoses of GW among U.S. service members before and after the availability of the quadrivalent HPV (HPV4) vaccine in 2006. Incidence rates of GW diagnoses markedly declined among female service members in the HPV4 vaccine-eligible age range from 2007 (following introduction of the HPV4 vaccine) through 2010. In contrast, among women 25 years and older and men of all age groups, annual rates of GW diagnoses remained relatively low and stable from 2000 through 2010. The higher rates of diagnoses of GWs among female than male service members reflect the effects of routine periodic gynecologic screening. Slight increases in the incidence of GW diagnoses among men between 2010 and 2012 may in part reflect the repeal of the U.S. military's "Don't Ask Don't Tell" policy.

Human papillomavirus seroprevalence among men entering military service and seroincidence after ten years of service.

Vaccination against human papillomavirus (HPV) is recommended to prevent cervical cancer among women. Vaccinating men against human papillomavirus (HPV) can prevent penile, anal, and oral cancers, anogenital warts, and the transmission of HPV to their sexual partners. This study characterized HPV acquisition among male military members by evaluating both seroprevalence at entry into service and seroincidence of HPV infection after ten years of service. At entry, 29 of 200 (14.5%) male service members were positive for HPV serotypes 6, 11, 16, or 18. Of 199 initially seronegative for at least one of the four HPV serotypes, 68 (34.2%) seroconverted to one or more serotypes at ten years; more than one-third of these were seropositive for oncogenic HPV serotypes. This estimate of HPV seroprevalence among male military accessions is higher than that reported among U.S. civilian males. Vaccination to prevent genital warts and cancers resulting from HPV infection may decrease health care system burdens. Further analyses are warranted to understand the potential costs and benefits of a policy to vaccinate male service members.

Weight changes in euthyroid patients undergoing thyroidectomy.

BACKGROUND: Thyroidectomized patients frequently report weight gain resistant to weight loss efforts, identifying their thyroidectomy as the event precipitating subsequent weight gain. We wished to determine whether recently thyroidectomized euthyroid patients gained more weight over 1 year than matched euthyroid patients with preexisting hypothyroidism. METHODS: We performed a retrospective chart review of subjects receiving medical care at an academic medical center. One hundred twenty patients had their weight and thyroid status documented after thyroidectomy and achievement of euthyroidism on thyroid hormone replacement, and one year later. Three additional groups of 120 patients with preexisting hypothyroidism, no thyroid disease, and thyroid cancer were matched for age, gender, menopausal status, height, and weight. Anthropometric data were documented at two time points 1 year apart. We compared the weight changes and body mass index changes occurring over a 1-year period in the four groups. RESULTS: Patients with recent postsurgical hypothyroidism gained 3.1 kg during the year, whereas matched patients with preexisting hypothyroidism gained 2.2 kg. The patients without thyroid disease and those with iatrogenic hyperthyroidism gained 1.3 and 1.2 kg, respectively. The weight gain in the thyroidectomized group was significantly greater than that in the matched hypothyroid group (p-value 0.004), the group without thyroid disease (p-value 0.001), and the patients with iatrogenic hyperthyroidism (p-value 0.001). Within the thyroidectomized group, the weight gain in menopausal women was greater than in either premenopausal women (4.4 vs. 2.3 kg, p-value 0.007) or men (4.4 vs. 2.5 kg, p-value 0.013). CONCLUSION: Patients who had undergone thyroidectomy in the previous year did, in fact, gain more weight than their matched counterparts with preexisting hypothyroidism. In addition, all patients with hypothyroidism, even though treated to achieve euthyroidism, experienced more weight gain than both subjects without hypothyroidism and subjects with iatrogenic hyperthyroidism. The greatest weight gain in the thyroidectomized group was in menopausal women. These data raise the question of an unidentified factor related to taking thyroid hormone replacement that is associated with weight gain, with an additional intriguing effect of thyroidectomy itself. Menopausal status confers additional risk. These groups should be targeted for diligent weight loss efforts.

Second primary breast, endometrial, and ovarian cancers in Black and White breast cancer survivors over a 35-year time span: effect of age.

Breast cancer incidence increases with age and exhibits a Black-to-White crossover around age 45. Breast cancer survivors are at a significantly elevated risk of developing a second primary breast or gynecological cancer compared with the general population. The purpose of this study was to determine whether a similar crossover occurs in hormonally related second primary breast, endometrial, or ovarian cancers in Black and White women. The Surveillance, Epidemiology, and End Results' Registry 9 was used to follow 415,664 White and 39,887 Black female breast cancer survivors, diagnosed at age 19 or older, for a second primary breast, endometrial, or ovarian cancer between 1973 and 2007. Cumulative incidence curves were generated; Pepe and Mori's test was used to test for significance. Second primary breast cancer followed the incidence pattern of the first primary breast cancer in Black and White women diagnosed before age 45. It was opposite of the pattern of first primary breast cancer in Black and White women diagnosed at age 45 or later. Second primary endometrial and ovarian cancers paralleled the incidence pattern of first primaries of the same anatomic site among Black and White women, independent of the age at diagnosis of the first primary breast cancer. Despite the Black-to-White crossover of first primary breast cancer around age 40, the incidence of hormonally related second primaries does not appear affected by the age at diagnosis of the first primary.

Menopause and menopausal symptoms after ovarian artery embolization: a comparison with uterine artery embolization controls.

PURPOSE: To determine the impact on menstrual status and menopausal symptoms of ovarian artery embolization (OAE) to supplement uterine embolization (UAE) for uterine leiomyomas. MATERIALS AND METHODS: A single-center case-control study was conducted in women who underwent UAE for leiomyomas. Between May 2004 and July 2009, 77 patients underwent unilateral or bilateral OAE during UAE procedures. Contemporaneous control subjects undergoing UAE alone were identified based on age and race. Questionnaires queried menstrual cycle regularity, onset of menopause, hormone use, and subsequent leiomyoma interventions, as well as the Menopause Rating Scale (MRS), a validated menopausal symptom questionnaire. Records were reviewed for baseline clinical and procedure data. Case and control subjects were compared for baseline characteristics and outcomes with the use of appropriate statistics, with the primary outcome the summary score on the MRS. RESULTS: Of 154 patients, 51 case subjects and 49 control subjects responded to the MRS (65%). Case subjects had greater tumor volumes (median, 129.3 cm(3) vs 69.3 cm(3) in control subjects; P = .0252) and longer fluoroscopy times (mean, 20.5 min vs 14 min in control subjects; P < .0001), with no other differences. There was a lower mean MRS score in the OAE group (total mean MRS score, 7.4 in case subjects and 8.9 in control subjects; P = .023), indicating fewer menopausal symptoms and no difference in menstrual regularity or frequency of onset of menopause. Of six patients who underwent bilateral OAE and responded, all reported continued menstrual cycles. CONCLUSIONS: Compared with standard UAE, the addition of OAE does not appear to precipitate the onset of menopause nor increase menopausal symptom severity.

Effectiveness of elective unilateral uterine artery embolization: a case-control study.

PURPOSE: To evaluate the effectiveness of elective unilateral uterine artery embolization (UAE) in limited fibroid disease. MATERIALS AND METHODS: A review of 1,431 UAE recipients at a single institution identified 76 who underwent unilateral embolization, most in the setting of anatomic variants or technical failure. A total of 28 had intentional unilateral UAE because of unilateral disease on magnetic resonance (MR) imaging with supply from only the ipsilateral uterine artery on angiography. These 28 case-group patients were compared with a control group of 28 patients who underwent bilateral UAE contemporaneously. Outcome measures included a chief symptom resolution score, fluoroscopy time, tumor infarction rate, patient satisfaction, analgesia requirements, and maximum pain score. Baseline characteristics and outcome measures were compared with t tests, Pearson χ(2) tests, analyses of variance, and nonparametric tests. RESULTS: Three-month clinical follow-up and postprocedure MR imaging were available for 25 of the case-group patients. The unilateral UAE group had fewer analgesia doses demanded (28.8 vs 57.5; P = .049), lower total analgesia dose (22.8 mg vs 34.5 mg; P = .029), shorter fluoroscopy time (10.9 min vs 13.4 min; P = .013), and lower maximum pain score (3.7 vs 5.7; P = .003). There were no differences in chief symptom resolution score (2.1 vs 1.9; P = .27), satisfaction score (4.0 vs 4.0; P = .72), or complete tumor infarction (92% vs 88%; P = .64). CONCLUSIONS: Unilateral UAE in appropriately selected patients has similar clinical results as standard bilateral UAE and is associated with reduced fluoroscopy time and postprocedural pain.

Age modifies the response to recombinant human thyrotropin.

BACKGROUND: A standardized protocol is used to administer recombinant human thyrotropin (rhTSH) in preparation for diagnostic studies and treatment in patients with thyroid cancer. The expectation is that serum TSH concentrations will peak on the day after the second injection and will be sufficiently elevated to stimulate uptake of radioiodine. We wished to test the hypothesis that TSH concentrations achieved after rhTSH injection are influenced by age. METHODS: Patients with thyroid cancer undergoing diagnostic radioiodine scanning were identified by chart review. Serum TSH concentrations were documented 24 and 72 hours after two rhTSH injections (days 3 and 5, respectively). Responses were subdivided into four ascending patient age groups: <35, 35-49, 50-64, and >64 years. TSH concentrations after rhTSH administration were documented according to patient age. RESULTS: There was a significant correlation between the serum TSH concentrations at both days 3 and 5 and patient age (p < 0.0001). None of the other factors examined (gender, menopausal status, weight, body mass index, baseline TSH, serum creatinine, and estimated glomerular filtration rate) were significant in multivariate analyses. The mean TSH concentration on day 3 increased significantly when patients were divided into the aforementioned groups of ascending age (96, 107, 142, and 196 mIU/L, p < 0.0001). Day 5 concentrations increased in a similar manner. CONCLUSIONS: Both days 3 and 5 TSH concentrations were higher in older individuals after rhTSH administration. This finding did not appear to be related to body weight, body mass index, or glomerular filtration rate in a simple manner. The TSH concentration achieved may be a result of complex interactions between distribution within fat and muscle body compartments, hepatic function, and renal function. Prospective studies could examine whether the magnitude of the TSH elevation after rhTSH administration affects diagnostic or therapeutic efficacy.

Age and the thyrotropin response to hypothyroxinemia.

CONTEXT: Some studies suggest altered pituitary functioning and TSH production with aging. OBJECTIVE: Our objective was to test the hypothesis that less TSH production occurs despite comparable hypothyroxinemia with advancing age. DESIGN: We retrospectively studied adult outpatients of all ages with confirmed hypothyroidism and documented their TSH and free T4 concentrations. PARTICIPANTS: Two populations of 112 patients were subdivided into four age groups: 1) patients newly diagnosed with primary hypothyroidism and 2) thyroid cancer patients undergoing l-T4 withdrawal in preparation for diagnostic or therapeutic radioiodine. MAIN OUTCOME MEASURE: The relationship between paired free T-4 and TSH concentrations and patient age was studied. RESULTS: With spontaneous hypothyroidism, the mean TSH concentration decreased nonsignificantly in each ascending age group with comparable free T4 (FT4) concentrations (<35 yr, 69 mIU/liter; 35-49 yr, 49 mIU/liter; 50-64 yr, 43 mIU/liter; >64 yr, 29 mIU/liter). With iatrogenic hypothyroidism, the mean TSH concentration decreased significantly in each ascending age group (<35 yr, 156 mIU/liter; 35-49 yr, 115 mIU/liter; 50-64 yr, 74 mIU/liter; >64 yr, 46 mIU/liter; P<0.001) despite similar FT4 concentrations. The relationship between the log-transformed TSH and FT4 was significantly and inversely affected by age in multivariate analyses in both spontaneous hypothyroidism (P=0.0005) and in iatrogenic hypothyroidism (P<0.0001). CONCLUSIONS: Age modifies the pituitary set point or response to comparably reduced free T4 concentrations, resulting in lesser serum TSH elevation in older individuals. This phenomenon occurs with both spontaneous and iatrogenic hypothyroidism. This may be an adaptive response in normal aging or a pathological alteration of pituitary function with age.

Bilateral versus unilateral femoral access for uterine artery embolization: results of a randomized comparative trial.

PURPOSE: To determine if uterine embolization via bilateral femoral puncture reduces fluoroscopy time with a similar frequency of puncture site complications compared with unilateral puncture. MATERIALS AND METHODS: Patients presenting for uterine artery embolization (UAE) for leiomyomata at a single institution were randomly assigned to receive unilateral or bilateral femoral punctures. Procedures were performed in a standardized fashion. Patients were blinded to the puncture site with an opaque dressing. Outcome measures included fluoroscopy time, dose-area product (DAP), procedure time, and puncture site pain after treatment. Baseline characteristics of the two groups and outcome measures were compared with the use of t tests, analyses of variance, Pearson chi(2) tests, and nonparametric tests. RESULTS: Fifty-seven patients consented to participate: 22 received bilateral punctures and 35 received unilateral puncture. Bilateral puncture procedures had less fluoroscopy time (13 minutes vs 16.6 minutes; P = .0033), less procedure time (54.9 min vs 62.9 min; P = .026), and fewer angiographic images (46.5 vs 68.3; P < .001). There was no difference in DAP (12,986 muGy/cm(2)for bilateral vs 16,237 muGy/cm(2)for unilateral; P = .35). Groins that were punctured had greater-although still minor-pain than unpunctured groins at 24 hours (visual analog pain scores, 1.45 for punctured groins vs 0 for unpunctured groins; P = .039) and 48 hours (scores of 1 vs 0; P = .018). There were no complications in either group. CONCLUSIONS: Bilateral femoral puncture during UAE was associated with reduced fluoroscopy time and procedure time, minor puncture site pain, and no increase in complications.

Pediatric acute lymphoblastic leukemia and exposure to pesticides.

Organophosphates are pesticides ubiquitous in the environment and have been hypothesized as one of the risk factors for acute lymphoblastic leukemia (ALL). In this study, we evaluated the associations of pesticide exposure in a residential environment with the risk for pediatric ALL. This is a case-control study of children newly diagnosed with ALL, and their mothers (n = 41 child-mother pairs) recruited from Georgetown University Medical Center and Children's National Medical Center in Washington, DC, between January 2005 and January 2008. Cases and controls were matched for age, sex, and county of residence. Environmental exposures were determined by questionnaire and by urinalysis of pesticide metabolites using isotope dilution gas chromatography-high-resolution mass spectrometry. We found that more case mothers (33%) than controls (14%) reported using insecticides in the home (P < 0.02). Other environmental exposures to toxic substances were not significantly associated with the risk of ALL. Pesticide levels were higher in cases than in controls (P < 0.05). Statistically significant differences were found between children with ALL and controls for the organophosphate metabolites diethylthiophosphate (P < 0.03) and diethyldithiophosphate (P < 0.05). The association of ALL risk with pesticide exposure merits further studies to confirm the association.

Quality of interventional radiology literature: a review of articles published in JVIR and CVIR.

PURPOSE: To evaluate the quality of reporting of clinical studies published in two interventional radiology journals. MATERIALS AND METHODS: Two investigators reviewed all articles reporting the outcomes from therapies in 12 consecutive months of Journal of Vascular and Interventional Radiology (JVIR) (August 2007 to July 2008) and CardioVascular and Interventional Radiology (CVIR) (July/August 2007 to May/June 2008). The included studies were evaluated by means of a score sheet adapted from the Consolidated Standards of Reporting Trials criteria. The score sheet was comprised of 22 categories, with each given a score of 0-2. These scores were summed (maximum score, 44) and the comparative results analyzed by using the Wilcoxon rank sum and chi(2) tests. RESULTS: A total of 129 articles were reviewed from JVIR and 86 from CVIR. JVIR's mean score was 23.3 +/- 4.9, which was significantly higher than CVIR's mean score of 19.8 +/- 5.7 (P< .0001). Prospective studies comprised 38% (49 of 129) of JVIR's articles and 35% (31 of 86) of CVIR's studies (P = .9076). The mean sample sizes were larger for JVIR than for CVIR (130.8 and 66.3, respectively) (P = .0173). Both journals primarily published case series (112/129 [86.8%] for JVIR and 76/86 [88%] for CVIR). Only six of the 129 articles (4.6%) in JVIR and seven of the 87 (8.1%) in CVIR were randomized studies. Key weaknesses in reporting include lack of randomization, blinding of outcome assessment, sample size analysis, and proper reporting of outcomes. CONCLUSIONS: Articles published in both journals displayed substantial weaknesses that potentially limit the validity of their conclusions.

Endogenous thyrotropin and triiodothyronine concentrations in individuals with thyroid cancer.

BACKGROUND: Thyroid hormone suppression therapy is associated with decreased recurrence rates and improved survival in patients with differentiated thyroid cancer. Recently higher baseline thyrotropin (TSH) levels have been found to be associated with a postoperative diagnosis of differentiated thyroid cancer. Our objective was to confirm whether preoperative TSH levels were higher in patients who were diagnosed with differentiated thyroid cancer after undergoing thyroidectomy, compared with patients who were found to have benign disease. We also sought to determine whether thyroid hormone levels were lower in the patients with malignancy. METHODS: The study was a retrospective analysis of a prospective study. The study setting was the General Clinical Research Center of an Academic Medical Center. Participants were 50 euthyroid patients undergoing thyroidectomy. Thyroxine, triiodothyronine (T(3)), and TSH levels were documented in patients prior to their scheduled thyroidectomy. Following thyroidectomy, patients were divided into those with a histologic diagnosis of either differentiated thyroid cancer or benign disease. Preoperative thyroid profiles were correlated with patients' postoperative diagnoses. RESULTS: All patients had a normal serum TSH concentration preoperatively. One-third of the group was diagnosed with thyroid cancer as a result of their thyroidectomy. These patients had a higher serum TSH level (mean = 1.50 mIU/L, CI 1.22-1.78 mIU/L) than patients with benign disease (mean = 1.01 mIU/mL, CI 0.84-1.18 mIU/L). There was a greater risk of having thyroid cancer in patients with TSH levels in the upper three quartiles of TSH values, compared with patients with TSH concentrations in the lowest quartile of TSH values (odd ratio = 8.7, CI 2.2-33.7). Patients with a thyroid cancer diagnosis also had lower T(3) concentrations measured by liquid chromatography tandem mass spectrometry (mean = 112.6 ng/dL, CI 103.8-121.4 ng/dL) than did patients with a benign diagnosis (mean 129.9 ng/dL, CI 121.4-138.4 ng/dL). CONCLUSION: These data confirm that higher TSH concentrations, even within the normal range, are associated with a subsequent diagnosis of thyroid cancer in individuals with thyroid abnormalities. This further supports the hypothesis that TSH stimulates the growth or development of thyroid malignancy during its early or preclinical phase. We also show for the first time that patients with thyroid cancer also have lower T(3) levels than patients with benign disease.