Mary Ann O'Riordan

Effect of Reducing the Dose of Stavudine on Body Composition, Bone Density, and Markers of Mitochondrial Toxicity in HIV-Infected Subjects: A Randomized, Controlled Study

BACKGROUND Stavudine is widely used in developing countries. Lipoatrophy and mitochondrial toxicity have been linked to stavudine use, but it is unclear whether switching to a lower dose can reduce these toxicities while maintaining human immunodeficiency virus (HIV) suppression. METHODS HIV-infected subjects receiving standard-dose stavudine with undetectable HIV type 1 RNA for > or =6 months were randomized (ratio, 3:2) to receive one-half of the stavudine dose (switch arm) or to maintain the dose (continuation arm) while continuing to receive all other prescribed antiretrovirals. The following measurements were obtained at baseline and week 48: fasting lactate, pyruvate, and lipid levels; results of whole-body dual-energy x-ray absorptiometry; and mitochondrial DNA (mtDNA) measurements in fat and peripheral blood mononuclear cells. Change from baseline to week 48 was compared within and between groups. RESULTS Twenty-four patients (79% of whom were men and 79% of whom were African American; median age, 45 years) were enrolled in the study, 15 were enrolled in the switch arm, and 9 were enrolled in the continuation arm. The median duration of stavudine treatment was 55 months (range, 21-126 months). The median CD4 cell count was 558 cells/mm(3) (range, 207-1698 cells/mm(3)). At baseline, the study arms had similar demographic characteristics and laboratory indices, except for body mass index, total lean body mass, and triglyceride levels (all of which were higher in the switch arm). Three patients (2 in the switch arm) discontinued the study because of study-unrelated reasons. CD4 cell counts remained unchanged. At 48 weeks, 6 patients (4 [27%] in the switch arm and 2 [22%] in the continuation arm) had detectable HIV RNA levels (median, 972 copies/mL; range, 60-49,400 copies/mL). All patients with detectable HIV RNA levels reported significant lapses in treatment adherence; none exhibited mutations in HIV genotype. After the treatment switch, significant changes from study entry to week 48 were noted only for lactate level (median change, -0.27 mmol/L; range, -1.2 to 0.25 mmol/L; P = .02) and fat mtDNA (median change, 40 copies/cell; range, -49 to 261 copies/cell; P = .02). In the continuation arm, a significant loss of bone mineral density was seen at week 48 (median change, -1.7%; range, -6.3% to 0.8%; P = .02). The only significant between-group difference was the change in bone mineral density from baseline (P = .003). CONCLUSIONS Reducing stavudine dose by one-half increased fat mtDNA and decreased lactate levels, suggesting improvement in mitochondrial indices while preserving HIV suppression in subjects who maintained adherence. A significant loss of bone mineral density was seen in patients receiving standard-dose stavudine but not in those receiving low-dose stavudine. These results suggest that switching to low-dose stavudine may improve mitochondrial indices while maintaining virological suppression.

High prevalence of overweight and obesity in females with phenylketonuria

The primary treatment for phenylketonuria (PKU) is a low phenylalanine diet together with an amino acid-based, phenylalanine-free formula. Thus, PKU patients tend to consume a diet enriched in carbohydrates which could predispose to obesity. Studies in the 1980s and 1990s demonstrated that school-age phenylketonuria (PKU) patients have a higher mean body weight compared to a control population. However, no recent studies in the United States PKU population have examined whether this trend has persisted or whether adolescents are also affected. To investigate whether pediatric PKU populations (ages 2-20 years) in two major metropolitan areas of the United States (Cleveland, OH and Houston, TX) have a higher than expected percentage of overweight (BMI≥85th percentile) relative to the general population in the United States (NHANES), a retrospective chart review of PKU patients born between 1990 and 2008 and followed in Cleveland, OH (Rainbow Babies and Childrens Hospital/University Hospitals Case Medical Center) and in Houston, TX (Texas Childrens Hospital) was performed. Based on data from the U.S., 40% of pediatric PKU patients were overweight or obese. However, the percentage of overweight females (55%) and obese females (33%) is 1.8× and 2.1× higher respectively than expected based on comparison data from U.S. children. Further studies are necessary to identify potential strategies for prevention of excessive weight gain in children with PKU, especially in females.

A Statewide Collaborative to Reduce Pediatric Surgical Site Infections

BACKGROUND: Surgical site infections (SSIs) are preventable events associated with significant morbidity and cost. Few interventions have been tested to reduce SSIs in children. METHODS: A quality improvement collaboration was established in Ohio composed of all referral children’s hospitals. Collaborative leaders developed an SSI reduction bundle for selected cardiac, orthopedic, and neurologic operations. The bundle was composed of 3 elements: prohibition of razors for skin preparation, chlorhexidine-alcohol use for incisional site preparation, and correct timing of prophylactic antibiotic administration. The incidence of SSIs across the collaborative was compared before and after institution of the bundle. The association between 1 of the bundle elements, namely correct timing of antibiotic prophylaxis, and the proportion of centers achieving 0 SSIs per month was measured. RESULTS: Eight pediatric hospitals participated. The proportion of months in which 0 SSIs per center was recorded was 56.9% before introduction of the bundle, versus 81.8% during the intervention (P < .001). Correct timing of preoperative prophylactic antibiotics also significantly improved; 39.4% of centers recorded correct timing in every eligible surgical procedure per month (“perfect timing”) before the intervention versus 78.7% after (P < .001). The achievement of 0 SSIs per center in a given month was associated with the achievement of perfect antibiotic timing for that month (P < .003). CONCLUSIONS: A statewide collaborative of children’s hospitals was successful in reducing the occurrence of SSIs across Ohio.

Relationships among Depressive Symptoms, Sexually Transmitted Infections, and Pregnancy in African-American Adolescent Girls

STUDY OBJECTIVE To explore relationships among depressive symptoms, sexually transmitted infections (STI), and pregnancy in African-American adolescent girls. DESIGN Retrospective chart review. SETTING A hospital-based outpatient practice serving primarily African-American patients. PARTICIPANTS A total of 126 female patients ages 13-19 years who had ligase chain reaction (LCR) for N. gonorrhoeae and C. trachomatis. METHODS Charts were reviewed for history of STI, history of pregnancy, LCR results, and a history of depressive symptoms as indicated by standardized provider notes and patient self-administered questionnaire. Data are compared using Fishers exact test. RESULTS Mean age was 16.6 years (+/-1.6 years); 19.8% of participants had a history of depressive symptoms, 40.5% had a history of STI, 8.7% had a prior pregnancy, and 18.2% had a positive LCR. Of patients with a history of depressive symptoms, 64% had a history of STI compared to 34.6% of those without depressive symptoms (P = 0.01). A positive LCR was found in 20% of patients with a history of depressive symptoms and 17.8% of patients without (P = 0.78). Of patients with a history of depressive symptoms, 12% had a prior pregnancy compared to 7.9% without such history (P = 0.45). CONCLUSIONS African-American adolescent females in our clinic with a history of depressive symptoms were more likely to have a history of STI. A greater percentage of patients with a history of depressive symptoms also had prior pregnancies and/or current STI. Sexually active adolescent girls should be screened for depressive symptoms as part of their evaluation for sexual risk behaviors.

Arterial stiffness in HIV-infected youth and associations with HIV-related variables

ABSTRACT Children and young adults infected with HIV are at elevated risk for cardiovascular disease (CVD). However, scarce data exist on the utility of non-invasive methods to diagnose subclinical CVD, such as pulse wave velocity (PWV), a non-invasive measure of arterial stiffness. The objectives of this study were to assess the relationship of carotid-femoral PWV with subclinical atherosclerosis measured by carotid intima-media thickness (IMT), compare measurements to healthy controls, and evaluate variables associated with PWV in HIV-infected youth. One hundred and one 8–25 year-old subjects on stable antiretroviral therapy with low-level viremia or an undetectable HIV-1 RNA were enrolled, along with 86 healthy controls similar in age, sex and race. There was no significant difference in PWV between groups (median (Q1, Q3): 5.7 (5.2, 6.3) vs 5.7 (4.9, 6.5) m/s; P = 0.81). Among the HIV-infected subjects, PWV was positively correlated with both internal carotid artery (R = 0.31, P = 0.02) and carotid bulb IMT (R = 0.29, P = 0.01). In multivariable regression, only current alcohol consumption and systolic blood pressure were independently associated with PWV in the HIV-infected group (where current alcohol consumption and higher systolic blood pressure were associated with higher PWV); whereas, age, body mass index, and current marijuana use were associated with PWV in healthy controls. In this study of PWV in HIV-infected youth, measures of arterial stiffness were not different between subjects and controls. However, in HIV-infected youth, there was a significant association between PWV and carotid IMT, as well as between PWV and current alcohol consumption. Thus, PWV may have potential as a useful, non-invasive method to assess CVD risk in HIV-infected youth, but further investigation is needed.

Awareness of a rape crisis center and knowledge about sexual violence among high school adolescents

STUDY OBJECTIVE This study examined awareness among adolescents of a local rape crisis center as well as their knowledge about sexual violence. DESIGN The Cleveland Rape Crisis Center (CRCC) conducts sexual violence prevention programs for high school students. A written, anonymous survey was distributed to students prior to the start of the program. Students were asked if they had heard of the CRCC; knowledge about sexual violence was assessed with a series of 7 statements (rape myths) that participants identified as true or false. Surveys were reviewed retrospectively. Analyses were carried out for individual questions and frequencies compared using chi-square analysis. RESULTS A total of 1633 surveys were collected; 1118 (68.5%) participants were female and 514 (31.5%) were male; ages ranged from 12 to 19 years. Respondents described themselves as being of European descent (45.9%), African descent (26.2%), or mixed race (17.7%). Just over half (863, 52.9%) of survey respondents had heard of the CRCC. Over half (950, 58.2%) of participants answered 5 or more questions correctly (range of correct answers 0 to 7). In general, more participants who were aware of the CRCC were able to identify statements about rape correctly (P < .01 for statements 1, 4, 5, 6, and 7, P < .001 for ≥ 5 correct). Age, gender, and race were all significantly associated with knowledge about rape. Females were consistently more likely to get an answer correct, as were participants of European descent. CONCLUSION Awareness of the CRCC was associated with increased knowledge about sexual violence.

Adult and child automated immature granulocyte norms are inappropriate for evaluating early-onset sepsis in newborns

Automated haematology analysers are increasingly being used. Normal ranges for automated immature granulocyte counts (IG%) are described in adults and children as <1%, but are not reported for newborns, who often have complete blood count with differential in evaluation for early‐onset sepsis. Therefore, this study aimed to describe IG% during the first 48 hours of life (HOL) in newborns and determine the clinical factors affecting IG%.