Laura J. Benjamins

Practice Guideline: Evaluation and Management of Abnormal Vaginal Bleeding in Adolescents

Abnormal vaginal bleeding is a common cause for concern among adolescents and their families, as well as a frequent cause of visits to the emergency department and health care provider. While there are many causes of abnormal vaginal bleeding, the most likely cause among otherwise healthy adolescents is dysfunctional uterine bleeding (DUB) resulting from an immature hypothalamic-pituitaryovarian axis, which results in anovulatory cycles and unpredictable bleeding. However, abnormal vaginal bleeding also may be the presenting symptom of a more serious underlying condition or problem. Furthermore, depending on the cause and severity of the bleeding, significant morbidity and mortality may be associated with it. This article will discuss many of the common causes of DUB, as well as the diagnostic work-up and management for this condition.

Evaluation and Management of Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) was first described in 1935 by Stein and Levanthal (1935) in the American Journal of Obstetrics and Gynecology. Yet, it remains a syndrome that is confusing to many patients and practitioners in terms of its presentation, work-up, and management. There is a spectrum of presenting complaints and physical findings as well as overlap with other disorders, such as the metabolic syndrome. PCOS affects about 5% to 10% of women in their reproductive years (Asuncion et al., 2000; Diamanti-Kandarakis, 2008; Knochenhauer et al., 1998), and can be associated with infertility, uterine changes, and endocrinopathies. Furthermore, as we are seeing an increase in obesity among our younger patients, particularly in the United States (Molnar, 2004; Ogden et al., 2006), we are likely to be identifying more adolescent patients with this syndrome. Recognizing the presenting signs and symptoms and knowing the proper diagnostic tests and treatment options for PCOS is therefore important. DIAGNOSTIC CRITERIA Adolescents with hirsutism, acne, obesity, and/or irregular menses may raise concern of PCOS. Because the clinical presentations vary, it is important to have specific diagnostic criteria. The Androgen Excess and PCOS Society recently convened to review available data and provide a revised definition of PCOS based on current knowledge. The most current proposed criteria from the Society include the presence of all of the following (Azziz et al., 2009): 1. Hyperandrogenism: Hirsutism and/or hyperandrogenemia 2. Ovarian dysfunction: Oligoanovulation and/or polycystic ovaries 3. Exclusion of other androgen excess or related disorders

Persistently high perinatal transmission of HIV: assessment of risk factors.

Background: Despite dramatic decreases in rates of perinatal mother-to-child-transmission (PMTCT) of HIV in the United States, rates in some groups remain above the national average. Our objective was to examine factors contributing to a high rate of PMTCT of HIV. Methods: We conducted a retrospective chart review of HIV-exposed infants and their mothers referred to the University of Texas-Houston Pediatric HIV Clinic from January 2000 to June 2007. Results: Of 367 newborns studied, 22 (6%) acquired HIV infection perinatally. Associated risk factors included inadequate prenatal care, failure to receive antiretroviral therapy during pregnancy, detectable viral load and intravenous drug abuse. Conclusions: The composite rate of PMTCT in this high risk cohort was at least 3-fold higher than expected from the current standard of care. Reduction of rates of PMTCT in our population will require ensuring access to appropriate prenatal care, including delivery of antiretroviral therapy and addressing issues of illicit drug use.

Pelvic inflammatory disease in adolescents between the time of testing and treatment and after treatment for gonorrhoeal and chlamydial infection

In incarcerated adolescents, 13% developed pelvic inflammatory disease (PID) between the time of testing and treatment for chlamydial and gonorrhoeal infection, and 13% developed PID in the 30 days following single-dose treatment for one or both of these infections.

Prevalence of Sexually Transmitted Infections Among Adolescents Entering Child Protective Services

STUDY OBJECTIVE Persons aged 15-24 years have the highest rates of sexually transmitted infections (STIs). Adolescents in protective services custody may be at even greater risk of acquiring STIs, but little is known about the prevalence of STIs among this population. We therefore set out to assess the prevalence of STIs among adolescents seen in the Harris County Child Protective Services Clinic. DESIGN A retrospective chart review from January 2009 to December 2011 was conducted. SETTING AND PARTICIPANTS Patients aged 12-18 years seen for their intake physical examination at the Harris County Child Protective Services Clinic in Houston, Texas. MAIN OUTCOME MEASURES Main outcome measures included the number of positive tests for chlamydia, gonorrhea, syphilis, and HIV. Secondary measures included sexual history, use of condoms and contraception, and reports of drug and alcohol use. RESULTS Among 437 patients, 60% were female, their mean age was 15 years, and nearly half were African American. There were 27 cases of chlamydia, 12 of gonorrhea, 3 of syphilis, and none of HIV. Three of the teenagers who reported never having sex were positive for an STI. Being female, being older than 15 years, and having had sexual intercourse at least once were significant risk factors. CONCLUSION The prevalence of STIs in adolescents entering foster care was comparable to national averages. Recommending routine screening of all adolescents in this population is important to ensure better detection and treatment.

Recent Thymus Emigrant CD4+ T Cells Predict HIV Disease Progression in Patients With Perinatally Acquired HIV

BACKGROUND Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Incidence and predictors of antiretroviral resistance in perinatally HIV-1 infected children and adolescents.

OBJECTIVES Individuals with perinatally acquired HIV infection have benefited from antiretroviral therapy. However, they often have complex patterns of major resistance mutations that limit the effectiveness of available antiretroviral medications. Knowledge of incidence rates of major antiretroviral resistance mutations should provide a benchmark enabling comparisons of different HIV care delivery modalities. METHODS We test the hypothesis that incidence rate of major antiretroviral resistance mutations will decline with improvement in HIV care between 1998 and 2009 to NRTI, NNRTI, PI and triple class resistance in perinatally HIV infected individuals. Logistic regression is used to evaluate predictors of single and triple class resistance. RESULTS Sixty-six individuals are included from a total population of 97 perinatally HIV infected individuals. The incidence rate of NRTI, NNRTI, PI and triple class resistance decreases with decreasing age in parallel with the introduction of new HIV treatment regimens. The youngest children (born 2000-2007) are free of triple class resistance. Mono-therapy associates with major resistance mutations to NRTI (OR 8.7, CI 1.5-50.9, P 0.02); NNRTI exposure associates with major resistance mutations to NNRTI (OR 24.4, CI 5.7-104.5, P 0.01) and triple class resistance (OR 10.7, CI 1.8-67.1, P 0.01). Cumulative viral load is an important predictor of PI resistance (OR 4.0, CI 1.3-12.3, P 0.02). CONCLUSIONS There is a progressive decrease in the incidence rate of major resistance mutations to antiretroviral drugs and triple class resistance from the oldest to the youngest birth cohort; where adolescents have the highest risk of harboring resistant viruses. The incidence rate of major antiretroviral resistance mutations provides a benchmark for the comparative measurement of effectiveness of different HIV care delivery modalities.

Forkhead box protein 3+ regulatory T cells and Helios+ subset in perinatally acquired HIV

Forkhead box protein 3 (FoxP3)+ regulatory T cells (Tregs) are important not only in regulating the development of autoimmune conditions, but also in chronic infectious diseases. Given their cardinal function in suppressing immune activation, research has focused upon whether they play a detrimental role in chronic infections, particularly HIV. While the role of Tregs in HIV has been investigated intensively, it remains an unresolved topic. However, it is generally accepted that Tregs are susceptible to HIV infection and are preferentially preserved over conventional CD4+ T cells. It is unknown whether the peripheral‐induced or the thymic‐derived Tregs are more susceptible to HIV cytotoxicity. It has been recognized that Tregs can be segregated into two subsets based on Helios expression, with the vast majority being Helios+. This study examines the impact of HIV infection on total Tregs and their Helios subsets in a perinatal‐acquired HIV‐infected paediatric population. The finding indicates a selective expansion or survival of Tregs in association with CD4 depletion and increased viraemia. The Helios+ and Helios− subsets within Tregs appear to be equally affected. However, the Helios+ Tregs seem to be more preserved in patients with low CD4+ ≤ 25% and detectable plasma HIV RNA >20 copies/ml. In this group, the frequencies of Tregs are increased, but their numbers appear insufficient to restrain immune activation. In conclusion, our findings suggest that both Helios subsets of Tregs are susceptible to HIV infection and are preferentially preserved compared to conventional CD4+ T cells.

Honey Pacifier Use Among an Indigent Pediatric Population

BACKGROUND: Use of honey pacifiers by infants presenting to a pediatric clinic at a county hospital in Houston, Texas, was observed by several of our staff members. Although we could not find any published studies linking the use of honey pacifiers to infant botulism, we also could not find any studies assessing the prevalence of honey pacifier use in general. METHODS: We conducted a cross-sectional, descriptive study using a novel survey that had 19 items. The survey was administered to the parents of children up to age 12 months presenting to a county hospital pediatric clinic for well-child care in Houston, Texas, from February 2010 to April 2011. RESULTS: There were 397 respondents. Approximately 11% of the respondents reported using honey pacifiers with their infant children. Reasons for use included tradition, infant preference, and perceived health benefits (eg, helps with constipation or colic). Approximately 20% of the honey pacifier users and 23% of the entire group reported knowledge of honey potentially causing an illness in children <12 months of age. Nearly 40% of all respondents also reported using herbal or folk remedies. CONCLUSIONS: Honey pacifier use was relatively common among this population, seen in ∼1 out of 10 respondents. A majority of the mothers surveyed (∼80%) were unaware of the potential dangers of giving honey to infants under age 12 months. Herbal medicine use was also common.

CHOICES-TEEN: Reducing Substance-Exposed Pregnancy and HIV Among Juvenile Justice Adolescent Females

Objective: The feasibility and acceptability of CHOICES-TEEN—a three-session intervention to reduce overlapping risks of alcohol-exposed pregnancy (AEP), tobacco-exposed pregnancy (TEP), and HIV—was assessed among females in the juvenile justice system. Method: Females aged 14–17 years on community probation in Houston, TX, were eligible if presenting with aforementioned health risks. Outcome measures—obtained at 1- and 3-months postbaseline—included the Timeline Followback, Client Satisfaction Questionnaire-8, session completion/checklists, Working Alliance Inventory–Short, and open-ended questions. Twenty-two participants enrolled (82% Hispanic/Latina; mean age = 16). Results: The results suggest strong acceptability and feasibility with high client satisfaction and client/therapist ratings, 91% session completion, and positive open-ended responses. All youth were at risk at baseline, with the following proportions at reduced risk at follow-up: AEP (90% at 1 month, 71.4% at 3 months), TEP (77% of smokers [n = 17] at reduced risk at 1 month, 50% at 3 months), and HIV (52.4% at 1 month, 28.6% at 3 months).