Pangaja Paramsothy

Longitudinal analysis of bacterial vaginosis: Findings from the HIV epidemiology research study

OBJECTIVE To determine the natural history of bacterial vaginosis in women with or at risk for human immunodeficiency virus (HIV). METHODS A cohort of 854 HIV‐infected women and 434 HIV‐uninfected women from four US sites was followed prospectively with gynecologic exams every 6 months over a 5‐year period. The prevalence, incidence, persistence, and severity of bacterial vaginosis, which was defined using a Gram‐staining scoring system, were calculated using generalized estimating equation methods. RESULTS In adjusted analyses, HIV‐infected women had a higher prevalence of bacterial vaginosis than HIV‐uninfected women (adjusted odds ratio [OR] 1.29; 95% confidence interval [CI] 1.08, 1.55). Although HIV‐infected women were not more likely to have incident infections, they were more likely to have persistence of their infections (adjusted OR 1.49; 95% CI 1.18, 1.89). Similarly, immunocompromised women (CD4+ cell count less than 200 cells/μL) were more likely than HIV‐infected women with higher CD4+ cell counts (more than 500 cells/μL) to have prevalent (adjusted OR 1.29; 95% CI 1.03, 1.60) and persistent (adjusted OR 1.38; 95% CI 1.01, 1.91) bacterial vaginosis infections, but not more likely to have incident infections. Immunocompromised women had more severe bacterial vaginosis by both clinical criteria (adjusted OR 1.40; 95% CI 1.08, 1.82) and by Gram‐staining criteria (adjusted OR 1.50; 95% CI 1.12, 2.00). CONCLUSIONS Bacterial vaginosis is more prevalent and persistent among HIV‐infected women, particularly among those who are immunocompromised. Immunocompromised women are more likely than HIV‐infected women with higher CD4+ cell counts to have severe bacterial vaginosis.

The Effect of Highly Active Antiretroviral Therapy on Human Papillomavirus Clearance and Cervical Cytology

OBJECTIVE: To examine the association of highly active antiretroviral therapy (HAART) with human papillomavirus (HPV) clearance and progression or regression of cervical cytological abnormalities in women with human immunodeficiency virus (HIV). METHODS: Five hundred thirty-seven women with HIV participating in the HIV Epidemiology Research Study, an observational, multisite cohort study, were evaluated semiannually from 1996 to 2000. Cervical Pap tests were collected for cervical cytology. Testing for HPV was conducted by polymerase chain reaction. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals (CIs). Number needed to treat (NNT) at 2 years was calculated for HAART. RESULTS: Among women with cervical squamous intraepithelial lesions, HAART was associated with an increased likelihood of HPV clearance (hazard ratio 4.5, 95% CI 1.2–16.3, NNT 22.4). Use of HAART was not associated with an increased likelihood of HPV clearance among women with normal cervical cytology (hazard ratio 1.7, 95% CI 0.9–3.1, NNT 6.5) or atypical squamous cells of undetermined significance cytology (hazard ratio 1.0, 95% CI 0.4–2.5, NNT 174.0). Use of HAART was not significantly associated with an increased likelihood of cervical cytologic regression (hazard ratio 1.3, 95% CI 1.0–1.7, NNT 10.9) or cervical cytologic progression (hazard ratio 0.7, 95% CI 0.6–1.0, NNT 12.8). CONCLUSION: Among women with preexisting abnormal cervical cytology, HAART was associated with enhanced HPV clearance but not with Pap test regression. Close monitoring of women with HIV for cervical cytologic abnormalities, regardless of HAART treatment status, is warranted. LEVEL OF EVIDENCE: II

High-risk human papillomavirus reactivation in human immunodeficiency virus-infected women: Risk factors for cervical viral shedding

OBJECTIVE: To evaluate the presence of and estimate risk factors for reactivation of latent high-risk human papillomavirus (HPV) cervical infection in human immunodeficiency virus (HIV)-infected and HIV-uninfected women. METHODS: Data from 898 women in the HIV Epidemiology Research Study (HERS) were used to evaluate cervical HPV latency and reactivation. Prior exposure to HPV types (16, 18, 31, 35, and 45) was determined by serologic testing at enrollment, and cervical shedding of HPV was detected by polymerase chain reaction at 6-month intervals. Human papillomavirus cervical shedding and sexual history were used to estimate rates of reactivation and recurrence. Repeated measures survival analysis was used to estimate hazard ratios and 95% confidence intervals for reactivation and recurrence. Rates of total HPV shedding (recurrence and reactivation) during follow-up were assessed by HIV status and rate ratios were calculated. RESULTS: Reactivation of latent HPV infections was observed in HIV-infected women, but few reactivation events were identified in HIV-uninfected women. Factors consistently associated with reactivation in HIV-infected women included CD4 count less than 200/mm3 and age younger than 35 years. Women infected with HIV had 1.8 to 8.2 times higher rates of viral shedding (reactivation plus recurrence) compared with HIV-uninfected women. CONCLUSION: Women with a history of cervical HPV infection may be at risk of reactivation of latent viral infection even in the absence of sexual activity, and this risk is higher in women with HIV infection. LEVEL OF EVIDENCE: II

Vulvar, vaginal, and perianal intraepithelial neoplasia in women with or at risk for human immunodeficiency virus.

OBJECTIVE: To compare the incidence of vulvar, vaginal, and perianal intraepithelial neoplasia among human immunodeficiency virus (HIV)–infected women with a group of well-matched high-risk HIV-uninfected controls. METHODS: A total of 192 HIV-infected and 88 uninfected women at high risk for HIV were followed up prospectively in Providence, Rhode Island during a 6-year period. Pap tests and cervicovaginal lavage for human papillomavirus detection and typing were performed at baseline and every 6 months thereafter. All women referred for colposcopy underwent a full colposcopic evaluation, including the vulvar, vaginal, and perianal regions. Unadjusted hazard ratios with 95% confidence intervals were calculated for development of vulvar, vaginal, and perianal intraepithelial neoplasia using univariable Cox proportional hazards models. An incidence analysis was performed by calculating Kaplan-Meier survival curves for development of intraepithelial neoplasia. RESULTS: At baseline, 3 (1.6%) of the 192 HIV-infected women and none of the 88 HIV-uninfected women had vulvar, vaginal, and perianal intraepithelial neoplasia. During the study, 16 of 189 (8.5%) HIV-infected women and 1 of 88 (1.1%) HIV-uninfected women developed vulvar, vaginal, and perianal intraepithelial neoplasia. The incidence of vulvar, vaginal, or anal intraepithelial neoplasia was 1.96 per 100 person years for the HIV-infected women and 0.26 per 100 person-years for the HIV-uninfected women (P = .03). CONCLUSION: Human immunodeficiency virus–infected women had more vulvar, vaginal, and perianal intraepithelial lesions compared with HIV-uninfected women. Furthermore, the incidence rates were higher than has been found in HIV-infected women in other similar cohorts. LEVEL OF EVIDENCE: II-2

Effect of HIV Infection on Atypical Squamous Cells of Undetermined Significance

BACKGROUND Detection of atypical squamous cells of undetermined significance (ASCUS) is a cervical cytologic finding that is suggestive but not definitive of squamous intraepithelial lesions (SILs). METHODS We examined the risk, characteristics, and progression of ASCUS in women with and without human immunodeficiency virus (HIV) infection. Cervical Papanicolou (Pap) test and colposcopy data were obtained at the first 10 semiannual visits for the HIV Epidemiology Research study of 774 HIV-infected and 480 demographically similar, HIV-uninfected women in the United States. Multiple logistic regression models and Cox proportional hazards models were utilized. RESULTS ASCUS was more common among HIV-infected women (odds ratio [OR], 1.6 [95% confidence interval {CI}, 1.3-2.0] to 2.6 [95% CI, 1.9-3.6]) after adjustment for human papillomavirus (HPV) infection and other risk factors (e.g., race, condyloma, and prior Pap test result). Among women with normal Pap test results at enrollment, the cumulative incidence of ASCUS was 78% among HIV-infected women and 38% among HIV-uninfected women. HIV-infected and HIV-uninfected women with ASCUS did not differ by prevalence of indices of inflammation (inflammation on Pap test and leukocytes on cervical gram stain). HPV infection, including high risk types, was more common among HIV-infected women with ASCUS. Among women with ASCUS, 60% of HIV-infected and 25% of HIV-uninfected women developed SILs (P < .01). Compared with HIV-infected women with higher CD4+ lymphocyte counts, HIV-infected women with CD4+ lymphocyte counts < 200 cells/microL were more likely to present subsequently with a SIL detected by Pap test (OR, 1.7; 95% CI, 0.8-3.6). CONCLUSIONS Higher risk of SIL following the appearance of ASCUS among HIV-infected women, especially women with low CD4+ lymphocyte counts, supports the need for follow up with colposcopy and histologic examination, as indicated, to allow early detection and treatment of SIL.

Design and Methodological Considerations of the Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida

PURPOSE Care of children with spina bifida has significantly advanced in the last half century, resulting in gains in longevity and quality of life for affected children and caregivers. Bladder dysfunction is the norm in patients with spina bifida and may result in infection, renal scarring and chronic kidney disease. However, the optimal urological management for spina bifida related bladder dysfunction is unknown. MATERIALS AND METHODS In 2012 the Centers for Disease Control and Prevention convened a working group composed of pediatric urologists, nephrologists, epidemiologists, methodologists, community advocates and Centers for Disease Control and Prevention personnel to develop a protocol to optimize urological care of children with spina bifida from the newborn period through age 5 years. RESULTS An iterative quality improvement protocol was selected. In this model participating institutions agree to prospectively treat all newborns with spina bifida using a single consensus based protocol. During the 5-year study period outcomes will be routinely assessed and the protocol adjusted as needed to optimize patient and process outcomes. Primary study outcomes include urinary tract infections, renal scarring, renal function and bladder characteristics. The protocol specifies the timing and use of testing (eg ultrasonography, urodynamics) and interventions (eg intermittent catheterization, prophylactic antibiotics, antimuscarinic medications). Starting in 2014 the Centers for Disease Control and Prevention began funding 9 study sites to implement and evaluate the protocol. CONCLUSIONS The Centers for Disease Control and Prevention Urologic and Renal Protocol for the Newborn and Young Child with Spina Bifida began accruing patients in 2015. Assessment in the first 5 years will focus on urinary tract infections, renal function, renal scarring and clinical process improvements.

Abnormal vaginal cytology in HIV-infected and at-risk women after hysterectomy.

Objective:To determine the frequency of and risk factors for abnormal vaginal Papanicolaou smears in HIV-infected women after hysterectomy. Methods:Data were from the HIV Epidemiology Research (HER) study, a prospective multisite study of HIV-infected and uninfected women. Semiannual vaginal Papanicolaou smears and colposcopy data were obtained from 102 HIV-infected and 46 at-risk women who had hysterectomy either before or during the study. Analytic models used include Cox proportional hazards (women with hysterectomy during the study) and multiple logistic regressions, which corrected for repeated measures (all women). Results:Among the HIV-infected women, evidence of cervical intraepithelial neoplasia before or at hysterectomy was associated with abnormal cytology during follow-up; 63% had squamous intraepithelial lesions (SIL) on vaginal Papanicolaou smears following hysterectomy. CD4 counts of <200 cells/μL at hysterectomy and HIV viral load of >10,000 copies/mL at hysterectomy were predictive of SIL vaginal cytology. Prevalent SIL vaginal cytology was associated with low CD4 count and human papillomavirus risk type. Of the 102 HIV-infected women, 16 (16%) had vaginal intraepithelial neoplasia on biopsy. Conclusions:The high rate of SIL on vaginal Papanicolaou smears and the presence of high-grade vaginal intraepithelial neoplasia among HIV-infected women after hysterectomy demonstrate the need for continued follow-up for lower genital tract lesions.

National Estimates of Hospital Use by Children With HIV Infection in the United States: Analysis of Data From the 2000 KIDS Inpatient Database

OBJECTIVES. The purpose of this research was to describe hospital use patterns of HIV-infected children in the United States. STUDY DESIGN. We analyzed a nationwide, stratified probability sample of 2.5 million hospital discharges of children and adolescents during the year 2000, weighted to 7.3 million discharges nationally. We excluded discharges after hospitalizations related to pregnancy/childbirth and their complications and discharges of neonates <1 month of age and of patients >18 years of age. Diagnoses were identified through the use of the Clinical Classification Software with grouping of related diagnoses. RESULTS. We estimated that there were 4107 hospitalizations of HIV-infected children in 2000 and that these hospitalizations accounted for ∼

Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy

100 million in hospital charges and >30000 hospital days. Infections, including sepsis and pneumonia, were among the most frequent diagnoses in such hospitalizations, followed by diagnoses related to gastrointestinal conditions, nutritional deficiencies and anemia, fluid/electrolyte disorders, central nervous system disorders, cardiovascular disorders, and respiratory illnesses. Compared with hospitalizations of non-HIV-infected children, hospitalizations of HIV-infected ones were more likely to be in urban areas, in pediatric/teaching hospitals, and in the Northeast, and the expected payer was more likely to be Medicaid (77.6% vs 37.2%). Compared with children without HIV, those with HIV tended to be older (median age: 9.5 years vs 5.2 years), to have been hospitalized longer (mean: 7.8 days vs 3.9 days), and to have incurred higher hospital costs (mean:

Neurobehavioral Concerns among Males with Dystrophinopathy Using Population-Based Surveillance Data from the Muscular Dystrophy Surveillance, Tracking, and Research Network

23221 vs