Statistically Significant Associations Between HPV33, HPV35, and HPV56 With Anal HSIL in a Population of MSMLWH.

OBJECTIVE: The aim of the study is to determine the prevalence of high-risk human papillomavirus (hrHPV) genotypes in men who have sex with other men and are living with HIV and the factors associated with anal high-grade squamous intraepithelial lesions (HSIL). METHODS: Anal swabs were collected for hrHPV genotyping from a cross-sectional group (N = 163) of eligible men who have sex with other men and are living with HIV attending a high-resolution anoscopy clinic. Persistent hrHPV infections were studied in a longitudinal subset (n = 37). Association of anal HSIL with specific hrHPV genotype(s) and with HIV-1 suppression was assessed. Pearson's χ2 test with continuity correction or Fisher's exact test was used to determine statistical significance (alpha = 0.05). RESULTS: Overall prevalence of hrHPV anal infections was 93.3% (152/163). Higher numbers of hrHPV genotypes were detected per sample in the HSIL group compared with less than or Low-grade squamous intraepithelial lesion (≤LSIL) group (p < .001). Proportion of participants infected with HPV33 was higher in the HSIL group (66.7%) than in ≤LSIL group (33.3%, p < .001), as was HPV35 (61.1% vs. 38.9%, p = .001) and HPV56 (56.7% vs. 43.3%, p = .022). HPV33 persistence was highly associated with HSIL (100%; 8/8) compared with ≤LSIL (0%; 0/8) (p < .001). Proportion of HIV-1 suppression (<200 cp/mL) was significantly lower among the HSIL group (80%; 48/60) compared with ≤LSIL group (95.1%; 97/102) (p = .006). CONCLUSIONS: Statistically significant associations existed between anal HSIL and HPV33, HPV35, and HPV56 infections, with HPV33 persistence, and with the lack of HIV-1 suppression. These findings emphasize the critical need for genotyping assays that differentiate more than just HPV16, HPV18 and a pool of "other" hrHPV genotypes and that have an intended use with anal specimens. Globally, this highest-risk population would benefit from the 9-valent vaccine to prevent infections and reduce anal cancer risk.

Health Care Utilization During the First 5½ Years of Authorized Service by Transgender U.S. Service Members (2016-2021).

Purpose: This study examined the utilization of gender-affirming health care by active-duty service members during the initial 5½ years that transgender and gender-diverse (TGD) individuals were authorized to serve in the U.S. military. The aim of this study was to inform policy discussions regarding inclusion of TGD individuals in the military. Methods: We conducted a retrospective cohort study using administrative health care data from the Military Data Repository (MDR). We assessed the association of demographic factors with the utilization of gender-affirming medical and surgical care. We calculated the incidence rate of initial TGD-related encounters and new prescriptions for gender-affirming hormones among Defense Department Service members between July 2016 and December 2021. Results: We identified 2481 service members with an initial health care encounter with an associated TGD-related diagnosis. More than half (53%) of these service members started gender-affirming hormones, and 14% underwent gender-affirming surgery. Mastectomies and hysterectomies accounted for more than 70% of surgeries. Service members made 3.22 initial encounters with a TGD-related diagnosis per 10,000 service members per year, with an overrepresentation of service members who were designated female in the MDR (8.62), junior enlisted (4.98), and young (4.64). Individuals designated female in the MDR comprised 17% of all service members but accounted for 46% of initial encounters, 51% of new prescriptions, and 73% of surgeries. Conclusion: The study revealed a higher-than-expected number of service members seeking gender-affirming care, particularly among service members designated female in the MDR. Military Health System clinicians provided most of this care, which may mitigate the cost of delivering this essential medical care.

Longitudinal Associations Between Perceived Discrimination and Suicidality in Youth.

Research among adults reveals robust associations between discrimination and suicidality. However, the relationship between discrimination and suicidality is understudied in youth. Participants in the Adolescent Brain Cognitive Development study (n = 10  312) completed a measure of discrimination based on multiple attributes. The Kiddie Schedule for Affective Disorders and Schizophrenia was administered 1 year later to assess depressive disorders and suicidality (ideation and behavior). Logistic regressions, adjusting for age, sex, race/ethnicity, family income, lifetime depressive disorders, and body composition were conducted. Adjusting for covariates, discrimination based on weight (OR: 2.19), race/ethnicity/color (OR: 3.21), and sexual orientation (OR: 3.83) were associated with greater odds of reporting suicidality 1 year later (ps < 0.025). Nationality-based discrimination was not significantly associated with suicidality. Compared with those reporting no discrimination, youths reporting discrimination based on 2 or more attributes had nearly 5 times greater odds of recent suicidality (OR: 4.72; P < .001). The current study highlights the deleterious impacts of discrimination on mental health among youths reporting multiple forms of discrimination.

Demonstrating a Statistically Significant Association Between Anal High-Grade Squamous Intraepithelial Lesion and Positive OncoE6 Anal Test in Men Who Have Sex With Men and Are Living With HIV.

OBJECTIVES: The aim of the study is to determine whether a positive OncoE6 Anal Test result has statistically significant higher odds of being associated with high-grade squamous intraepithelial lesion (HSIL) and to calculate sensitivity and specificity of this test for predicting HSIL in adult men who have sex with men and are living with HIV (MSMLWH). MATERIALS AND METHODS: Men living with HIV 18 years or older having ≥atypical squamous cells of undetermined significance-grade anal cytology results were eligible to enroll in this cross-sectional study. Anal samples were collected just before the high-resolution anoscopy procedure. OncoE6 Anal Test results were compared with histology, the reference standard. Sensitivity, specificity, and odds ratio were calculated using HSIL as the threshold. RESULTS: Two hundred seventy-seven consented MSMLWH were enrolled between June 2017 and January 2022. Of these, 219 (79.1%) had biopsies obtained and histology performed; 81 of 219 participants (37%) had 1 or more biopsies with HSIL results while the remaining 138 of 219 (63%) had only low-grade squamous intraepithelial lesion or were negative for dysplasia. Anal samples from 7 participants (8.6%, 7/81) with HSIL and 3 (2.2%, 3/138) with low-grade squamous intraepithelial lesion had positive OncoE6 Anal Test results. Odds of having HSIL were 4.26 times higher among participants testing positive for HPV16/HPV18 E6 oncoprotein(s) (OR = 4.26, 95% CI = 1.07-16.95, p = .04). The OncoE6 Anal Test demonstrated excellent specificity, 97.83% (93.78-99.55), but poor sensitivity, 8.64% (3.55-17.0). CONCLUSIONS: In this highest-risk population for anal cancer, one could combine the OncoE6 Anal Test, having excellent specificity, with the anal Pap test, having higher sensitivity. Patients found having both an abnormal anal Pap and positive OncoE6 Anal Test result could be triaged for rapid scheduling of their high-resolution anoscopy.

Association of Gonadotropin-Releasing Hormone Analogue Use With Subsequent Use of Gender-Affirming Hormones Among Transgender Adolescents.

Importance: Gonadotropin-releasing hormone analogue (GnRHa) use during puberty improves mental health among transgender and gender-diverse (TGD) adolescents. In previous studies, most (96.5%-98.1%) TGD adolescents who started GnRHa subsequently started gender-affirming hormones (GAH), raising concerns that GnRHa use promotes later use of GAH. Objective: To determine whether GnRHa use among TGD adolescents is associated with increased subsequent GAH use. Design, Setting, and Participants: This is a retrospective cohort study of administrative records collected between 2009 and 2018. The current analysis was completed in August 2022. Participants were enrolled in the US Military Healthcare System (MHS) with an initial TGD-related encounter occurring between ages 10 and 17 years. Exposures: GnRHa use. Main Outcomes and Measures: Initiation of GAH. Results: The 434 patients were a mean (SD) of 15.4 (1.6) years old at the time of their first TGD-related encounter; 312 (71.9%) were assigned female at birth, and 300 (69.1%) had an enlisted insurance sponsor. GnRHa use was more common among patients who were assigned male at birth (28 patients [23.0%]) than those assigned female (42 patients [13.5%]), but GAH use was not. Socioeconomic status was not associated with GnRHa or GAH use. Compared with older patients (aged 14-17 years), those who were younger (aged 10-13 years) at the time of the initial TGD-related encounter had a higher rate of GnRHa use (32 patients [57.1%] vs 38 patients [10.1%]) and a longer median time to starting GAH. The median interval from the date of the initial encounter to starting GAH decreased over time, from 2.3 years (95% CI, 1.7-2.8 years) between October 2009 and December 2014 to 0.6 years (95% CI, 0.5-0.6 years) between September 2016 and April 2018. Patients who were prescribed GnRHa had a longer median time to starting GAH (1.8 years; 95% CI, 1.1-2.4 years) than patients who were not (1.0 years; 95% CI, 0.8-1.2 years) and were less likely to start GAH during the 6 years after their first TGD-related encounter (hazard ratio, 0.52; 95% CI, 0.37-0.71). Among 54 younger (aged 10-13 years) patients who were not eligible to start GAH at their first encounter, GnRHa use was associated with a longer median time to starting GAH, but age at the first TGD-related visit was not. Conclusions and Relevance: In this cohort study of TGD adolescents, GnRHa use was not associated with increased subsequent GAH use. These findings suggest that clinicians can offer the benefits of GnRHa treatment without concern for increasing rates of future GAH use.

Affirming Hormone Treatment for a Transgender Adolescent After a Venous Thromboembolic Event.

BACKGROUND: Medical affirmation, including gender-affirming hormones, is an essential component in the treatment of many transgender and gender-diverse youth. The risk of venous thromboembolism (VTE) during testosterone therapy for gender-affirming care is not fully elucidated. OBSERVATION: The case describes a 17-year-old transgender male treated with testosterone therapy who presented with an occlusive deep vein thrombosis of right axillary and subclavian veins. Testosterone level was 920 ng/dL at the time of the deep vein thrombosis, and he had no risk factors for VTE. A complete hypercoagulable workup was negative. CONCLUSIONS: The possibility of testosterone therapy as a risk factor for VTE may suggest the need to include this information during informed consent discussions. Long-term anticoagulation may be considered for those restarting testosterone therapy.

Long term survival outcomes of stage I mucinous ovarian cancer - A clinical calculator predictive of chemotherapy benefit.

OBJECTIVES: To determine the long-term potential benefit of adjuvant chemotherapy in subgroups of high-risk stage I mucinous ovarian cancer patients using a predictive scoring algorithm. METHODS: Data were collected from the National Cancer Database from 2004 to 2014. Based on demographic and surgical characteristics, a novel 10-year survival prognostic scoring system was developed using Cox regression. RESULTS: There were 2041 eligible patients with stage I mucinous ovarian cancer including 1362 (67%) with stage IA/IB disease, 598 (29%) with stage IC disease, and 81 (4%) with stage I disease not otherwise specified. Median age was 52 with a range of 13-90 years old. 737 (36%) patients were treated with adjuvant chemotherapy. Adjuvant chemotherapy was more common in patients with stage IC relative to stage IA/IB disease (69% vs. 21%, P < 0.001) or with poorly-differentiated relative to well-differentiated tumors (69% vs. 23%, P < 0.001). Unadjusted 10-year survival was 81% relative to 79% for patients treated with vs. without chemotherapy, respectively (P = 0.46). Patients were predicted to exhibit a low- or a high-risk of death using a multivariate Cox regression model with age, stage, grade, lymphovascular space invasion and ascites. Risk of death without vs. with adjuvant chemotherapy was similar in low-risk patients (88% vs. 84%; HR = 0.80, 95%CI = 0.56-1.15, P = 0.23) and worse in high-risk patients (51% vs. 74%; HR = 1.58, 95%CI: 1.05-2.38, P = 0.03) with stage I mucinous ovarian cancer. CONCLUSIONS: A predictive scoring algorithm may provide prognostic information on long-term survival and identify high-risk stage I mucinous ovarian cancer patients who might achieve a survival benefit from adjuvant chemotherapy.

Screening and Counseling Adolescents and Young Adults: A Framework for Comprehensive Care.

Healthy development is likely to occur when an adolescent's risk factors are limited and when protective factors are fostered. Healthy development is further encouraged when youth feel valued, empowered, and form healthy social connections. Threats to the well-being of adolescents typically result from experimentation and psychosocial stressors. SSHADESS (strengths, school, home, activities, drugs, emotions/eating, sexuality, safety) is a mnemonic to facilitate collection of psychosocial history of critical life dimensions emphasizing strengths within a youth's life experience instead of solely focusing on risks, which in isolation can provoke feelings of shame. Because adolescents are more likely to access health care and share sensitive information when confidentiality is assured, clinicians should regularly offer confidential screening and counseling. When limited for time, a brief psychosocial screen may include current stressors, availability of a confidant, and school or work experience as a proxy for well-being. Clinicians should provide education to prevent initiation of tobacco use. Long-acting reversible contraceptives are safe and effective in adolescents and should be offered as first-line options to prevent pregnancy. Sexually active females 24 years or younger should be screened for gonorrhea and chlamydia annually. Adolescents 12 years or older should be screened for major depressive disorder when systems are available to ensure accurate diagnosis, treatment, and follow-up. Adolescents with body mass index at the 95th percentile or higher should be referred for comprehensive behavioral interventions. Seatbelt use and avoidance of distracted or impaired driving should be discussed. Clinicians should discuss digital literacy and appropriate online boundary setting and display of personal information.

Chemotherapy alone for patients 75 years and older with epithelial ovarian cancer-is interval cytoreductive surgery still needed?

BACKGROUND: Patients ≥75 years old with ovarian cancer experience high perioperative morbidity, but recruitment into prospective trials to assess the role of surgery continues to be challenging. OBJECTIVE: To compare overall survival for patients ≥75 years old with ovarian cancer after chemotherapy alone vs neoadjuvant chemotherapy with interval cytoreductive surgery. STUDY DESIGN: Data were extracted from the National Cancer Data Base from 2004 to 2014. Kaplan-Meier and Cox proportional hazards models were used for statistical analyses. RESULTS: Of 1661 patients (median age: 79 years), most were white (88%) and had stage III-IV disease (95%), and 51% had serous histology. Of those who did not receive primary surgery, 58% had chemotherapy alone and the remainder had neoadjuvant chemotherapy with interval cytoreductive surgery. The use of neoadjuvant chemotherapy with interval cytoreductive surgery increased from 28% to 50% in years 2004-2007 to 2012-2014 (P<.001). Compared with neoadjuvant chemotherapy with interval cytoreductive surgery, chemotherapy-only patients were older (80 vs 78 years; P<.001) and had more advanced stage disease (98% vs 91%; P<.001). The 5-year overall survival of the entire study group was 14%; those who underwent neoadjuvant chemotherapy with interval cytoreductive surgery had overall survival of 25% compared with only 7% in chemotherapy alone group (P<.001). In multivariable analysis, neoadjuvant chemotherapy with interval cytoreductive surgery (hazard ratio, 0.44; 95% confidence interval, 0.36-0.54; P<.001) was an independent predictor for improved survival. Older (80-84 years) age (hazard ratio, 1.35; 95% confidence interval, 1.12-1.63; P=.002), advanced (stage III-IV) disease (hazard ratio; 2.06, 95% confidence interval, 1.37-3.09; P=.001), and clear cell histology (hazard ratio; 2.17, 95% confidence interval, 1.10-4.28; P=.03) portended for worse outcome. CONCLUSION: Patients ≥75 years with ovarian cancer old have an overall poor prognosis. Receiving neoadjuvant chemotherapy followed by interval cytoreductive surgery is associated with greater overall survival compared to chemotherapy alone.

Amenorrhea: A Systematic Approach to Diagnosis and Management.

Menstrual patterns can be an indicator of overall health and self-perception of well-being. Primary amenorrhea, defined as the lifelong absence of menses, requires evaluation if menarche has not occurred by 15 years of age or three years post-thelarche. Secondary amenorrhea is characterized by cessation of previously regular menses for three months or previously irregular menses for six months and warrants evaluation. Clinicians may consider etiologies of amenorrhea categorically as outflow tract abnormalities, primary ovarian insufficiency, hypothalamic or pituitary disorders, other endocrine gland disorders, sequelae of chronic disease, physiologic, or induced. The history should include menstrual onset and patterns, eating and exercise habits, presence of psychosocial stressors, body weight changes, medication use, galactorrhea, and chronic illness. Additional questions may target neurologic, vasomotor, hyperandrogenic, or thyroid-related symptoms. The physical examination should identify anthropometric and pubertal development trends. All patients should be offered a pregnancy test and assessment of serum follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone levels. Additional testing, including karyotyping, serum androgen evaluation, and pelvic or brain imaging, should be individualized. Patients with primary ovarian insufficiency can maintain unpredictable ovary function and may require hormone replacement therapy, contraception, or infertility services. Functional hypothalamic amenorrhea may indicate disordered eating and low bone density. Treatment should address the underlying cause. Patients with polycystic ovary syndrome should undergo screening and intervention to attenuate metabolic disease and endometrial cancer risk. Amenorrhea can be associated with clinically challenging pathology and may require lifelong treatment. Patients will benefit from ample time with the clinician, sensitivity, and emotional support.

Measuring Community Prevalence of Trichomonas vaginalis Infection to Guide Local Screening Practices: A Process Improvement Project.

The Centers for Disease Control and Prevention suggests screening for Trichomonas vaginalis infection might be considered in high-prevalence populations. High asymptomatic infection rates and poor sensitivity of clinical diagnosis make it difficult to estimate local prevalence. Testing of ThinPrep samples can provide an estimate of local Trichomonas vaginalis infection rates and guide screening practices.

Disorders of Puberty: An Approach to Diagnosis and Management.

Disorders of puberty can profoundly impact physical and psychosocial well-being. Precocious puberty is pubertal onset before eight years of age in girls and before nine years of age in boys. Patients with early isolated pubertal changes, prepubertal linear growth, and no worrisome neurologic symptoms typically have a benign pattern of development and should be monitored in the appropriate clinical context. Among patients with true precocious puberty, or full activation of the hypothalamic-pituitary-gonadal axis, most girls have an idiopathic etiology, whereas it is commonly due to identifiable pathology on imaging in boys. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); thyroid function testing; and bone age radiography. Brain magnetic resonance imaging should be performed in girls younger than six years, all boys with precocious puberty, and children with neurologic symptoms. Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Constitutional delay of growth and puberty is a common cause of delayed puberty; however, functional or persistent hypogonadism should be excluded. History and physical examination should be followed by measurements of serum follicle-stimulating hormone, luteinizing hormone, and testosterone (boys) or estradiol (girls); and bone age radiography. Abnormal growth velocity necessitates assessment of serum thyroid function, prolactin, and insulinlike growth factor I. Boys 14 years and older and girls 13 years and older may benefit from sex steroid treatment to jump-start puberty. Referral to a pediatric endocrinologist may be warranted after the initial evaluation.

All Military Adolescents Are Not the Same: Sexuality and Substance Use among Adolescents in the U.S. Military Healthcare System.

Data examining sexuality and substance use among active duty and military-dependent youth is limited; however, these psychosocial factors have military implications. Adolescents and young adults aged 12-23 were recruited from an active-duty trainee clinic (n = 225) and a military pediatric clinic (n = 223). Active duty participants were more likely to be older, male, White, previous tobacco users, and report a history of sexual activity and less contraception use at their most recent intercourse, compared to the dependent group. Over 10% of all participants indicated attraction to members of the same gender or both genders. In logistic regression analysis, non-White participants were less likely to use contraception compared to White participants. Adolescents and young adults seen in military clinics frequently engage in high-risk behavior. Clinicians who care for military youth should assess their patient's psychosocial history. Further study of this population is warranted to identify factors that may influence risk and resilience.

Are HIV-infected men vulnerable to prostate cancer treatment disparities?

BACKGROUND: HIV-infected (HIV(+)) men face cancer treatment disparities that impact outcome. Prostate cancer treatment and treatment appropriateness in HIV(+) men are unknown. METHODS: We used electronic chart review to conduct a retrospective cohort study of 43 HIV(+) cases with prostate cancer and 86 age- and race-matched HIV-uninfected (HIV(-)) controls with prostate cancer, ages 40 to 79 years, from 2001 to 2012. We defined treatment appropriateness using National Comprehensive Cancer Network guidelines and the Charlson comorbidity index (CCI) to estimate life expectancy. RESULTS: Median age was 59.5 years at prostate cancer diagnosis. Median CD4(+) T-cell count was 459.5 cells/mm(3), 95.3% received antiretroviral therapy, and 87.1% were virally suppressed. Radical prostatectomy was the primary treatment for 39.5% of HIV(+) and 71.0% of HIV(-) men (P = 0.004). Only 16.3% of HIV(+) versus 57.0% of HIV(-) men received open radical prostatectomy (P < 0.001). HIV(+) men received more radiotherapy (25.6% vs. 16.3%, P = 0.13). HIV was negatively associated with open radical prostatectomy (OR = 0.03, P = 0.007), adjusting for insurance and CCI. No men were undertreated. Fewer HIV(+) men received appropriate treatment (89.2% vs. 100%, P = 0.003), due to four overtreated HIV(+) men. Excluding AIDS from the CCI still resulted in fewer HIV(+) men receiving appropriate treatment (94.6% vs. 100%, P = 0.03). CONCLUSION: Prostate cancer in HIV(+) men is largely appropriately treated. Under- or overtreatment may occur from difficulties in life expectancy estimation. HIV(+) men may receive more radiotherapy and fewer radical prostatectomies, specifically open radical prostatectomies. IMPACT: Research on HIV/AIDS survival indices and etiologies and outcomes of this prostate cancer treatment disparity in HIV(+) men are needed.

Amenorrhea: an approach to diagnosis and management.

Although amenorrhea may result from a number of different conditions, a systematic evaluation including a detailed history, physical examination, and laboratory assessment of selected serum hormone levels can usually identify the underlying cause. Primary amenorrhea, which by definition is failure to reach menarche, is often the result of chromosomal irregularities leading to primary ovarian insufficiency (e.g., Turner syndrome) or anatomic abnormalities (e.g., Müllerian agenesis). Secondary amenorrhea is defined as the cessation of regular menses for three months or the cessation of irregular menses for six months. Most cases of secondary amenorrhea can be attributed to polycystic ovary syndrome, hypothalamic amenorrhea, hyperprolactinemia, or primary ovarian insufficiency. Pregnancy should be excluded in all cases. Initial workup of primary and secondary amenorrhea includes a pregnancy test and serum levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and thyroid-stimulating hormone. Patients with primary ovarian insufficiency can maintain unpredictable ovarian function and should not be presumed infertile. Patients with hypothalamic amenorrhea should be evaluated for eating disorders and are at risk for decreased bone density. Patients with polycystic ovary syndrome are at risk for glucose intolerance, dyslipidemia, and other aspects of metabolic syndrome. Patients with Turner syndrome (or variant) should be treated by a physician familiar with the appropriate screening and treatment measures. Treatment goals for patients with amenorrhea may vary considerably, and depend on the patient and the specific diagnosis.

Pleural findings in a patient with persistent pulmonary effusions from systemic amyloidosis.

Persistent pleural effusions (PPE) occur in 1-2% of cases of systemic amyloidosis and have been postulated to result from direct disruption of the pleura by amyloid deposits. Patients are typically treated with percutaneous pleural drainage techniques. Pleural biopsies, done most commonly via percutaneous techniques, are infrequently obtained. The macroscopic and histologic pleural findings identified via video assisted thoracoscopic surgery (VATS) for these patients are lacking in the literature. In this case, we present the macroscopic and microscopic pleural findings in a patient who had VATS for the aetiologic diagnosis of PPE. The diagnosis of systemic amyloidosis was made from histologic analysis of the pleural biopsy.