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1.
PLoS One ; 8(1): e52206, 2013.
Article in English | MEDLINE | ID: mdl-23341895

ABSTRACT

BACKGROUND: The U.S. Family Smoking Prevention and Tobacco Control Act of 2009 requires updating of the existing text-only health warning labels on tobacco packaging with nine new warning statements accompanied by pictorial images. Survey and experimental research in the U.S. and other countries supports the effectiveness of pictorial health warning labels compared with text-only warnings for informing smokers about the risks of smoking and encouraging cessation. Yet very little research has examined differences in reactions to warning labels by race/ethnicity, education or income despite evidence that population subgroups may differ in their ability to process health information. The purpose of the present study was to evaluate the potential impact of pictorial warning labels compared with text-only labels among U.S. adult smokers from diverse racial/ethnic and socioeconomic subgroups. METHODS/FINDINGS: Participants were adult smokers recruited from two online research panels (n = 3,371) into a web-based experimental study to view either the new pictorial warnings or text-only warnings. Participants viewed the labels and reported their reactions. Adjusted regression models demonstrated significantly stronger reactions for the pictorial condition for each outcome salience (b = 0.62, p<.001); perceived impact (b = 0.44, p<.001); credibility (OR = 1.41, 95% CI = 1.22-1.62), and intention to quit (OR = 1.30, 95% CI = 1.10-1.53). No significant results were found for interactions between condition and race/ethnicity, education, or income. The only exception concerned the intention to quit outcome, where the condition-by-education interaction was nearly significant (p = 0.057). CONCLUSIONS: Findings suggest that the greater impact of the pictorial warning label compared to the text-only warning is consistent across diverse racial/ethnic and socioeconomic populations. Given their great reach, pictorial health warning labels may be one of the few tobacco control policies that have the potential to reduce communication inequalities across groups. Policies that establish strong pictorial warning labels on tobacco packaging may be instrumental in reducing the toll of the tobacco epidemic, particularly within vulnerable communities.


Subject(s)
Ethnicity , Internet , Nicotiana/adverse effects , Product Labeling , Racial Groups , Smoking Prevention , Adult , Demography , Educational Status , Female , Humans , Male , Smoking/epidemiology , Smoking Cessation , Socioeconomic Factors , United States/epidemiology , United States Food and Drug Administration
2.
J Clin Oncol ; 30(22): 2768-75, 2012 Aug 01.
Article in English | MEDLINE | ID: mdl-22734029

ABSTRACT

PURPOSE: Within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), we assessed the long-term disease-specific functioning among prostate cancer (PCa) survivors versus noncancer controls, the impact of trial arm (screening/usual care) on functioning, and the effect of treatment modality on functioning. PATIENTS AND METHODS: PCa survivors (n = 529), 5 to 10 years postdiagnosis, were frequency-matched to noncancer controls (n = 514) for race, screening center, year of enrollment, and trial arm. Participants completed a telephone interview regarding PCa-specific symptomatology. Weights accounted for patient selection from the five PLCO screening centers. Propensity-score methods were used to balance groups of interest with respect to demographic and medical characteristics. RESULTS: Weighted linear regression analyses revealed poorer sexual and urinary function among PCa survivors compared with noncancer controls (P < .001). Trial arm was not significantly related to any outcome (P > .31). Compared with radical prostatectomy patients (n = 201), radiation-therapy patients (n = 110) reported better sexual (P < .05) and urinary (P < .001) functioning but poorer bowel outcomes (P < .05). Survivors who received treatment combinations including androgen deprivation (n = 207) reported significantly poorer hormone-related symptoms compared with radical prostatectomy patients (P < .05). CONCLUSION This study demonstrated the persistence of clinically significant, long-term PCa treatment-related sexual and urinary adverse effects up to 10 years postdiagnosis. To our knowledge, this was the first comparison of prostate-related dysfunction among screened survivors versus screened noncancer controls and indicated that these long-term problems were attributable to PCa treatment and not to aging or comorbidities. Finally, differences in long-term adverse effects between treatment modalities are particularly relevant for patients and clinicians when making treatment decisions.


Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer , Lung Neoplasms/diagnosis , Ovarian Neoplasms/diagnosis , Prostatic Neoplasms/mortality , Aged , Female , Humans , Linear Models , Male , Middle Aged , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/therapy , Survivors
3.
Arthritis Rheum ; 64(3): 908-13, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22006113

ABSTRACT

OBJECTIVE: To investigate the efficacy of etanercept in improving the symptoms and underlying inflammation in patients with tumor necrosis factor receptor-associated periodic syndrome (TRAPS). METHODS: Fifteen patients with TRAPS were enrolled in a prospective, open-label, dose-escalation study. Patients recorded attacks, symptom severity, and use of ancillary medications in a daily diary. Blood samples were collected during each period and measured for levels of acute-phase reactants. Between 7 years and 9 years after the conclusion of the initial study, patients completed a followup survey and were evaluated to determine the long-term outcome of etanercept treatment. RESULTS: Etanercept treatment significantly attenuated the total symptom score and reduced the frequency of symptoms. Etanercept also reduced levels of acute-phase reactants, particularly during asymptomatic periods. During a 10-year followup period, patients continued to receive etanercept for a median of 3.3 years, with a number of patients switching to anti-interleukin-1ß receptor therapy or not receiving biologic agents, most frequently citing injection site reactions and lack of efficacy as reasons for discontinuation. However, patients continuing to receive etanercept had reduced symptoms at followup. CONCLUSION: Etanercept reduces symptoms and serum levels of inflammatory markers of TRAPS in a dose-dependent manner, but does not completely normalize symptoms or acute-phase reactant levels. Although long-term adherence to etanercept is poor, continuing to receive etanercept may provide continued symptomatic benefit.


Subject(s)
Familial Mediterranean Fever/drug therapy , Immunoglobulin G/therapeutic use , Immunologic Factors/therapeutic use , Receptors, Tumor Necrosis Factor/therapeutic use , Dose-Response Relationship, Drug , Drug Substitution , Etanercept , Humans , Prospective Studies , Receptors, Tumor Necrosis Factor, Type I , Remission Induction , Treatment Outcome
4.
Circ Cardiovasc Imaging ; 4(1): 33-41, 2011 Jan.
Article in English | MEDLINE | ID: mdl-21059858

ABSTRACT

BACKGROUND: Pluripotent stem cells represent one promising source for cellular cardiomyoplasty. In this study, we used cardiac magnetic resonance to examine the ability of highly enriched cardiomyocytes (CMs) derived from murine embryonic stem cells (ESC) to form grafts and improve contractile function of infarcted rat hearts. METHODS AND RESULTS: Highly enriched ESC-CMs were obtained by inducing cardiac differentiation of ESCs stably expressing a cardiac-restricted puromycin resistance gene. At the time of transplantation, enriched ESC-CMs expressed cardiac-specific markers and markers of developing CMs, but only 6% of them were proliferating. A growth factor-containing vehicle solution or ESC-CMs (5 to 10 million) suspended in the same solution was injected into athymic rat hearts 1 week after myocardial infarction. Initial infarct size was measured by cardiac magnetic resonance 1 day after myocardial infarction. Compared with vehicle treatment, treatment with ESC-CMs improved global systolic function 1 and 2 months after injection and significantly increased contractile function in initially infarcted areas and border zones. Immunohistochemistry confirmed successful engraftment and the persistence of α-actinin-positive ESC-CMs that also expressed α-smooth muscle actin. Connexin-43-positive sites were observed between grafted ESC-CMs but only rarely between grafted and host CMs. No teratomas were observed in any of the animals. CONCLUSIONS: Highly enriched and early-stage ESC-CMs were safe, formed stable grafts, and mediated a long-term recovery of global and regional myocardial contractile function after infarction.


Subject(s)
Embryonic Stem Cells/transplantation , Myocardial Contraction , Myocardial Infarction/therapy , Myocytes, Cardiac/transplantation , Stem Cell Transplantation/methods , Ventricular Dysfunction, Left/prevention & control , Analysis of Variance , Animals , Cells, Cultured , Disease Models, Animal , Female , Heart Ventricles/pathology , Magnetic Resonance Imaging/methods , Mice , Myocardial Infarction/complications , Rats , Time , Ventricular Dysfunction, Left/etiology
5.
PLoS Med ; 7(10)2010 Oct 05.
Article in English | MEDLINE | ID: mdl-20957191

ABSTRACT

BACKGROUND: Approximately 800,000 children die each year due to pneumococcal disease and >90% of these deaths occur in developing countries where few children have access to life-saving serotype-based vaccines. Understanding the serotype epidemiology of invasive pneumococcal disease (IPD) among children is necessary for vaccine development and introduction policies. The aim of this study was to systematically estimate the global and regional distributions of serotypes causing IPD in children <5 years of age. METHODS AND FINDINGS: We systematically reviewed studies with IPD serotype data among children <5 years of age from the published literature and unpublished data provided by researchers. Studies conducted prior to pneumococcal conjugate vaccine (PCV) introduction, from 1980 to 2007, with ≥12 months of surveillance, and reporting ≥20 serotyped isolates were included. Serotype-specific proportions were pooled in a random effects meta-analysis and combined with PD incidence and mortality estimates to infer global and regional serotype-specific PD burden. Of 1,292, studies reviewed, 169 were included comprising 60,090 isolates from 70 countries. Globally and regionally, six to 11 serotypes accounted for ≥70% of IPD. Seven serotypes (1, 5, 6A, 6B, 14, 19F, 23F) were the most common globally; and based on year 2000 incidence and mortality estimates these seven serotypes accounted for >300,000 deaths in Africa and 200,000 deaths in Asia. Serotypes included in both the 10- and 13-valent PCVs accounted for 10 million cases and 600,000 deaths worldwide. CONCLUSIONS: A limited number of serotypes cause most IPD worldwide. The serotypes included in existing PCV formulations account for 49%-88% of deaths in Africa and Asia where PD morbidity and mortality are the highest, but few children have access to these life-saving vaccines. Please see later in the article for the Editors' Summary.


Subject(s)
Pneumococcal Infections/classification , Serotyping/methods , Streptococcus pneumoniae/classification , Child, Preschool , Disease Progression , Humans , Infant , Infant, Newborn , Internationality , Pneumococcal Infections/blood , Pneumococcal Infections/prevention & control , Streptococcus pneumoniae/immunology , Vaccines, Conjugate/therapeutic use
6.
Patient Educ Couns ; 79(1): 25-9, 2010 Apr.
Article in English | MEDLINE | ID: mdl-19665860

ABSTRACT

OBJECTIVE: This study investigates HIV positive adolescents' health literacy and whether factors associated with health literacy in HIV-positive adults are associated with health literacy among HIV-positive adolescents. METHODS: Adolescents in this study were behaviorally and perinatally HIV-infected youth (n=186) from five U.S. cities. Participants had a mean age of 20.5, and 49.5% were male. RESULTS AND CONCLUSIONS: Contrary to findings for adult HIV-positive patients, among adolescents health literacy was not significantly associated with: medication adherence adjusting for age and education level; viral load; or self-efficacy to adhere to medication regimens. The only significant association was of health literacy with medical care received. PRACTICE IMPLICATIONS: Practice implications are discussed.


Subject(s)
Antiviral Agents/therapeutic use , Communication , HIV Infections/drug therapy , Health Literacy , Medication Adherence/statistics & numerical data , Adolescent , Adolescent Behavior , CD4 Lymphocyte Count , Child , Confidence Intervals , Female , Health Knowledge, Attitudes, Practice , Humans , Linear Models , Logistic Models , Male , Patient Acceptance of Health Care , Risk Reduction Behavior , Surveys and Questionnaires , United States , Young Adult
7.
Sex Transm Dis ; 36(7): 439-44, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19525889

ABSTRACT

BACKGROUND: Secondary transmission remains a significant concern among HIV-infected youth. Little is known, however, about how partner-specific sexual risk behaviors for the secondary transmission of HIV may differ between the 2 largest subgroups of HIV-positive youth, women-who-have-sex-with-men (WSM) and men-who-have-sex-with-men (MSM), METHODS: During 2003-2004, a convenience sample of HIV-infected youth, 13 to 24 years of age, were recruited from 15 Adolescent Medicine Trials Network clinical sites. Approximately 10 to 15 youth were recruited at each site. Participants completed an ACASI survey including questions about sex partners in the past year. Cross-sectional data analyses, including bivariate and multivariable regressions, using generalized estimating equations, were conducted during 2008 to compare recent partner-specific sexual risk behaviors between WSM and MSM. RESULTS: Of 409 participants, 91% (371) were included in this analysis, including 176 WSM and 195 MSM. Ninety-two percent (163 WSM, 177 MSM) provided information on characteristics of their sexual partners. There were significant differences between the 2 groups in recent partner-specific sexual risk behaviors including: lower rates of condom use at last sex among WSM (61% WSM vs. 78% MSM; P = 0.0011); a larger proportion of the sex partners of MSM reported as concurrent (56% MSM vs. 36% WSM; P = 0.0001); and greater use of hard drugs at last sex by MSM and/or their partner (18% MSM vs. 4% WSM; P = 0.0008). When measuring risk as a composite measure of sexual risk behaviors known to be associated with HIV transmission, both groups had high rates of risky behaviors, 74.7% among young MSM compared to 68.1% of WSM. CONCLUSIONS: These data suggest that recent partner-specific sexual risk behaviors for HIV transmission are high among young infected MSM and WSM. These findings suggest the need to offer interventions to reduce the secondary transmission of HIV to all HIV-positive youth in care. However, differences in risk behaviors between young MSM and WSM supports population-specific interventions.


Subject(s)
Adolescent Behavior , HIV Infections/transmission , Risk-Taking , Sexual Partners , Adolescent , Adult , Clinical Trials as Topic , Condoms/statistics & numerical data , Cross-Sectional Studies , Female , HIV Infections/epidemiology , Humans , Male , Sexual Behavior , Substance-Related Disorders/complications , Surveys and Questionnaires , Young Adult
10.
Am J Kidney Dis ; 51(6): 952-65, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18423809

ABSTRACT

BACKGROUND: Previous clinical trials showed that progression of coronary artery calcification (CAC) may be slower in hemodialysis patients treated with sevelamer than those treated with calcium-based phosphate binders. Because sevelamer decreases low-density lipoprotein cholesterol (LDL-C) levels, we hypothesized that intensive lowering of LDL-C levels with atorvastatin in hemodialysis patients treated with calcium acetate would result in CAC progression rates similar to those in sevelamer-treated patients. STUDY DESIGN: Randomized, controlled, open-label, noninferiority trial with an upper bound for the noninferiority margin of 1.8. SETTING & PARTICIPANTS: 203 prevalent hemodialysis patients at 26 dialysis centers with serum phosphorus levels greater than 5.5 mg/dL, LDL-C levels greater than 80 mg/dL, and baseline CAC scores of 30 to 7,000 units assessed by means of electron-beam computed tomography. INTERVENTIONS: 103 patients were randomly assigned to calcium acetate, and 100 patients to sevelamer for 12 months to achieve phosphorus levels of 3.5 to 5.5 mg/dL. Atorvastatin was added to achieve serum LDL-C levels less than 70 mg/dL in both groups. OUTCOMES & MEASUREMENTS: The primary end point was change in CAC score assessed by means of electron-beam computed tomography. RESULTS: After 12 months, mean serum LDL-C levels decreased to 68.8 +/- 22.0 mg/dL in the calcium-acetate group and 62.4 +/- 23.0 mg/dL in the sevelamer group (P = 0.3). Geometric mean increases in CAC scores were 35% in the calcium-acetate group and 39% in the sevelamer group, with a covariate-adjusted calcium acetate-sevelamer ratio of 0.994 (95% confidence interval, 0.851 to 1.161). LIMITATIONS: Treatment assignment was not blinded. The 1.8 a priori margin is large, CAC is a surrogate outcome, duration of treatment was short, and dropout rate was high. CONCLUSIONS: With intensive lowering of LDL-C levels for 1 year, hemodialysis patients treated with either calcium acetate or sevelamer experienced similar progression of CAC.


Subject(s)
Acetates/therapeutic use , Anticholesteremic Agents/therapeutic use , Calcinosis/prevention & control , Chelating Agents/therapeutic use , Coronary Artery Disease/prevention & control , Heptanoic Acids/therapeutic use , Polyamines/therapeutic use , Pyrroles/therapeutic use , Renal Dialysis , Atorvastatin , Calcium Compounds/therapeutic use , Disease Progression , Female , Humans , Male , Middle Aged , Prospective Studies , Sevelamer , Time Factors
11.
Antimicrob Agents Chemother ; 52(2): 631-7, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18025112

ABSTRACT

The primary objective of this study was to measure atazanavir-ritonavir and tenofovir pharmacokinetics when the drugs were used in combination in young adults with human immunodeficiency virus (HIV). HIV-infected subjects > or =18 to <25 years old receiving (> or =28 days) 300/100 mg atazanavir-ritonavir plus 300 mg tenofovir disoproxil fumarate (TDF) plus one or more other nucleoside analogs underwent intensive 24-h pharmacokinetic studies following a light meal. Peripheral blood mononuclear cells were obtained at 1, 4, and 24 h postdose for quantification of intracellular tenofovir diphosphate (TFV-DP) concentrations. Twenty-two subjects were eligible for analyses. The geometric mean (95% confidence interval [CI]) atazanavir area under the concentration-time curve from 0 to 24 h (AUC(0-24)), maximum concentration of drug in serum (C(max)), concentration at 24 h postdose (C(24)), and total apparent oral clearance (CL/F) values were 35,971 ng x hr/ml (30,853 to 41,898), 3,504 ng/ml (2,978 to 4,105), 578 ng/ml (474 to 704), and 8.3 liter/hr (7.2 to 9.7), respectively. The geometric mean (95% CI) tenofovir AUC(0-24), C(max), C(24), and CL/F values were 2,762 ng.hr/ml (2,392 to 3,041), 254 ng/ml (221 to 292), 60 ng/ml (52 to 68), and 49.2 liter/hr (43.8 to 55.3), respectively. Body weight was significantly predictive of CL/F for all three drugs. For every 10-kg increase in weight, there was a 10%, 14.8%, and 6.8% increase in the atazanavir, ritonavir, and tenofovir CL/F, respectively (P < or = 0.01). Renal function was predictive of tenofovir CL/F. For every 10 ml/min increase in creatinine clearance, there was a 4.6% increase in tenofovir CL/F (P < 0.0001). The geometric mean (95% CI) TFV-DP concentrations at 1, 4, and 24 h postdose were 96.4 (71.5 to 130), 93.3 (68 to 130), and 92.7 (70 to 123) fmol/million cells. There was an association between renal function, tenofovir AUC, and tenofovir C(max) and intracellular TFV-DP concentrations, although none of these associations reached statistical significance. In these HIV-infected young adults treated with atazanavir-ritonavir plus TDF, the atazanavir AUC was similar to those of older adults treated with the combination. Based on data for healthy volunteers, a higher tenofovir AUC may have been expected, but was not seen in these subjects. This might be due to faster tenofovir CL/F because of higher creatinine clearance in this age group. Additional studies of the exposure-response relationships of this regimen in children, adolescents, and adults would advance our knowledge of its pharmacodynamic properties.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/pharmacokinetics , HIV Infections/drug therapy , Oligopeptides/pharmacokinetics , Organophosphonates/pharmacokinetics , Pyridines/pharmacokinetics , Reverse Transcriptase Inhibitors/pharmacokinetics , Ritonavir/pharmacokinetics , Adenine/blood , Adenine/pharmacokinetics , Adenine/therapeutic use , Adolescent , Adult , Anti-HIV Agents/blood , Anti-HIV Agents/therapeutic use , Area Under Curve , Atazanavir Sulfate , Drug Interactions , Drug Therapy, Combination , Female , HIV Infections/virology , HIV-1/drug effects , Humans , Leukocytes, Mononuclear/chemistry , Male , Oligopeptides/blood , Oligopeptides/therapeutic use , Organophosphonates/blood , Organophosphonates/therapeutic use , Pyridines/blood , Pyridines/therapeutic use , Reverse Transcriptase Inhibitors/blood , Reverse Transcriptase Inhibitors/therapeutic use , Ritonavir/blood , Ritonavir/therapeutic use , Tenofovir
12.
J Urban Health ; 83(3): 506-22, 2006 May.
Article in English | MEDLINE | ID: mdl-16739051

ABSTRACT

Despite the considerable resources that have been dedicated to HIV prevention interventions and services over the past decade, HIV incidence among young people in the United States remains alarmingly high. One reason is that the majority of prevention efforts continue to focus solely on modifying individual behavior, even though public health research strongly suggests that changes to a community's structural elements, such as their programs, practices, and laws or policies, may result in more effective and sustainable outcomes. Connect to Protect is a multi-city community mobilization intervention that focuses on altering or creating community structural elements in ways that will ultimately reduce youth HIV incidence and prevalence. The project, which spans 6 years, is sponsored by the Adolescent Medicine Trials Network for HIV/AIDS Interventions at multiple urban clinical research sites. This paper provides an overview of the study's three phases and describes key factors in setting a firm foundation for the initiation and execution of this type of undertaking. Connect to Protect's community mobilization approach to achieving structural change represents a relatively new and broad direction in HIV prevention research. To optimize opportunities for its success, time and resources must be initially placed into laying the groundwork. This includes activities such as building a strong overarching study infrastructure to ensure protocol tasks can be met across sites; tapping into local site and community expertise and knowledge; forming collaborative relationships between sites and community organizations and members; and fostering community input on and support for changes at a structural level. Failing to take steps such as these may lead to insurmountable implementation problems for an intervention of this kind.


Subject(s)
HIV Infections/prevention & control , Health Promotion/methods , Urban Health , Adolescent , Adult , Community-Institutional Relations , HIV Infections/epidemiology , Humans , Incidence , Prevalence , Research Design , Residence Characteristics , United States/epidemiology
13.
Arch Pediatr Adolesc Med ; 159(8): 764-70, 2005 Aug.
Article in English | MEDLINE | ID: mdl-16061785

ABSTRACT

OBJECTIVES: To longitudinally follow a cohort of adolescents with human immunodeficiency virus (HIV) and to investigate long-term antiretroviral therapy adherence and factors associated with adherence. DESIGN, SETTING, AND PATIENTS: Adolescents infected with HIV (N = 231; mean age, 18.4 years; 72.7% female; 74.9% African American) from 13 cities throughout the United States were assessed at 3-month intervals. MAIN OUTCOME MEASURES: Self-reported adherence measures were validated by comparison with HIV-1 RNA viral load, and behavioral factors that may be associated with antiretroviral therapy adherence were assessed. RESULTS: At the initial visit, approximately 69% of the adolescents reported being adherent to antiretroviral therapy. Adolescents in the later HIV disease stage were less likely to be adherent compared with those in the earlier disease stage. Less alcohol use and being in school were associated with adherence by adolescents on weekends and over the preceding month. Longitudinal adherence was investigated among 65 subjects initially adherent with available information for at least 4 consecutive visits. The median time to nonadherence was 12 months, and failure to maintain adherence was significantly associated with younger age and depression. Among adolescents who attained an undetectable viral load, only about 50% maintained an undetectable viral load for the year. CONCLUSIONS: These findings indicate an urgent need for better interventions to assist adolescents with HIV in adhering to their medication regimens. Adolescents with advanced disease are likely to need more intervention. New treatments recently found effective for adolescent depression may assist in improving adherence for a majority of adolescents with HIV.


Subject(s)
Adolescent Behavior , Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Patient Compliance/statistics & numerical data , Adolescent , Adult , Age Factors , Alcohol Drinking/epidemiology , CD4 Lymphocyte Count , Cohort Studies , Depression/complications , Female , HIV Infections/epidemiology , HIV-1 , Humans , Interviews as Topic , Longitudinal Studies , Male , Multivariate Analysis , Proportional Hazards Models , RNA, Viral/analysis , Student Dropouts , United States/epidemiology , Viral Load
14.
Arch Neurol ; 62(7): 1073-80, 2005 Jul.
Article in English | MEDLINE | ID: mdl-16009761

ABSTRACT

OBJECTIVES: To identify asymptomatic boys with X-linked adrenoleukodystrophy who have a normal magnetic resonance image (MRI), and to assess the effect of 4:1 glyceryl trioleate-glyceryl trierucate (Lorenzo's oil) on disease progression. METHOD: Eighty-nine boys (mean +/- SD baseline age, 4.7 +/- 4.1 years; range, 0.2-15 years) were identified by a plasma very long-chain fatty acids assay used to screen at-risk boys. All were treated with Lorenzo's oil and moderate fat restriction. Plasma fatty acids and clinical status were followed for 6.9 +/- 2.7 years. Changes in plasma hexacosanoic acid levels were assessed by measuring the length-adjusted area under the curve, and a proportional hazards model was used to evaluate association with the development of abnormal MRI results and neurological abnormalities. RESULTS: Of the 89 boys, 24% developed MRI abnormalities and 11% developed both neurological and MRI abnormalities. Abnormalities occurred only in the 64 patients who were aged 7 years or younger at the time therapy was started. There was significant association between the development of MRI abnormalities and a plasma hexacosanoic acid increase. (For a 0.1-microg/mL increase in the length-adjusted area under the curve for the hexacosanoic acid level, the hazard ratio for incident MRI abnormalities in the whole group was 1.36; P = .01; 95% confidence interval, 1.07-1.72.) Results for patients aged 7 years or younger were similar (P = .04). CONCLUSIONS: In this single-arm study, hexacosanoic acid reduction by Lorenzo's oil was associated with reduced risk of developing MRI abnormalities. We recommend Lorenzo's oil therapy in asymptomatic boys with X-linked adrenoleukodystophy who have normal brain MRI results.


Subject(s)
Adrenoleukodystrophy/drug therapy , Adrenoleukodystrophy/pathology , Brain/pathology , Erucic Acids/therapeutic use , Triolein/therapeutic use , Adrenoleukodystrophy/genetics , Biomarkers/analysis , Child , Child, Preschool , Dietary Fats, Unsaturated , Drug Combinations , Fatty Acids/blood , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Risk Factors , Treatment Outcome
15.
N Engl J Med ; 351(22): 2295-301, 2004 Nov 25.
Article in English | MEDLINE | ID: mdl-15525714

ABSTRACT

BACKGROUND: The loss of half the U.S. supply of influenza vaccine due to contamination has created a critical shortage. Dose-sparing strategies that use intradermal delivery of vaccines may be one approach to consider. METHODS: We conducted a randomized, open-label trial outside the influenza season in 100 healthy adults 18 to 40 years of age to compare the immunogenicity and safety of intradermal immunization with influenza vaccine with standard intramuscular immunization. Subjects were randomly assigned to receive either a single intramuscular dose of 0.5 ml of trivalent influenza vaccine, containing at least 15 microg of hemagglutinin per strain, by means of a prefilled syringe or a single intradermal dose of 0.1 ml, containing at least 3 microg of hemagglutinin per strain, by means of a fine-gauge needle; both injections were in the deltoid region. Changes in the hemagglutination-inhibition (HAI) antibody titer were assessed by comparing geometric mean titers and fold increases relative to baseline values and by comparing changes in the seroconversion and seroprotection rates. Local and systemic adverse events were assessed after both types of vaccination. RESULTS: Subjects who received an intradermal injection with one fifth the standard dose of influenza vaccine had increases in the geometric mean HAI titer by a factor of 15.2 for the H1N1 strain in the vaccine, 19.0 for the H3N2 strain, and 12.4 for the B strain on day 21, as compared with respective increases by a factor of 14.9, 7.1, and 15.3 for the intramuscular injection of the standard dose. Seroconversion and seroprotection rates were similar in the two groups on day 21, ranging from 66 to 82 percent and 84 to 100 percent, respectively. Local reactions were significantly more frequent among recipients of intradermal injections than among recipients of intramuscular injections, but such reactions were mild and transient. CONCLUSIONS: In this study of young adults, intradermal administration of one fifth the standard intramuscular dose of an influenza vaccine elicited immunogenicity that was similar to or better than that elicited by intramuscular injection. Intradermal administration could be used to expand the supplies of influenza vaccine, but further studies are needed before this strategy can be recommended for routine use.


Subject(s)
Antibodies, Viral/blood , Influenza A virus/immunology , Influenza B virus/immunology , Influenza Vaccines/administration & dosage , Influenza Vaccines/immunology , Influenza, Human/prevention & control , Adolescent , Adult , Female , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Influenza Vaccines/adverse effects , Influenza, Human/immunology , Injections, Intradermal , Injections, Intramuscular , Male
16.
Kidney Int ; 65(5): 1914-26, 2004 May.
Article in English | MEDLINE | ID: mdl-15086935

ABSTRACT

BACKGROUND: Hyperphosphatemia underlies development of hyperparathyroidism, osteodystrophy, extraosseous calcification, and is associated with increased mortality in hemodialysis patients. METHODS: To determine whether calcium acetate or sevelamer hydrochloride best achieves recently recommended treatment goals of phosphorus

Subject(s)
Acetates/therapeutic use , Phosphorus/blood , Polyamines/therapeutic use , Renal Dialysis , Adult , Aged , Bicarbonates/blood , Calcium/blood , Calcium Compounds , Double-Blind Method , Epoxy Compounds/therapeutic use , Female , Humans , Hypercalcemia/blood , Hypocalcemia/blood , Male , Middle Aged , Parathyroid Hormone/blood , Polyethylenes/therapeutic use , Prospective Studies , Sevelamer
17.
Alcohol Clin Exp Res ; 27(8): 1278-85, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12966322

ABSTRACT

BACKGROUND: We investigated the relationship between educational attainment and drinking outcomes after discharge from inpatient treatment for alcohol dependence. METHODS: Between 1993 and 1996, we consecutively recruited 41 women and 60 men hospitalized for alcohol dependence and followed them up monthly for 1 year. We conducted structured interviews during hospitalization and at monthly intervals after discharge for 1 year. We examined the relationship between educational attainment before treatment and postdischarge drinking outcomes, including time to relapse. RESULTS: After covariate adjustment, educational level was a significant predictor of drinking outcomes. CONCLUSIONS: Lower levels of educational attainment before entry into treatment predicted shorter times to first drink and relapse in both women and men. The association of educational attainment and treatment outcome for alcohol dependence warrants further investigation.


Subject(s)
Achievement , Alcoholism/prevention & control , Alcoholism/psychology , Alcoholism/therapy , Chi-Square Distribution , Educational Status , Female , Follow-Up Studies , Humans , Male , Proportional Hazards Models , Prospective Studies , Secondary Prevention , Treatment Outcome
18.
J Nucl Med ; 44(8): 1263-6, 2003 Aug.
Article in English | MEDLINE | ID: mdl-12902416

ABSTRACT

UNLABELLED: The purpose of this investigation was to evaluate the use of a commercially available lactose-free fatty-meal food supplement, as an alternative to sincalide cholescintigraphy, to develop a standard methodology, and to determine normal gallbladder ejection fractions (GBEFs) for this supplement. METHODS: Twenty healthy volunteers all had negative medical histories for hepatobiliary and gallbladder disease, had no personal or family history of hepatobiliary disease, and were not taking any medication known to affect gallbladder emptying. All were prescreened with a complete blood cell count, comprehensive metabolic profile, gallbladder and liver ultrasonography, and conventional cholescintigraphy. Three of the 20 subjects were eliminated from the final analysis because of an abnormality in one of the above studies. RESULTS: After gallbladder filling on conventional cholescintigraphy, the subjects ingested the supplement and an additional 60-min study was acquired. GBEFs were calculated and ranged from 33% to 95% (mean +/- SD, 62.6% +/- 21.3%). Statistical analysis determined the lower range of normal to be 32.6%. Maximal gallbladder emptying occurred between 55 and 60 min. CONCLUSION: A standard methodology and normal GBEFs (> or =33%) were established for supplement-stimulated cholescintigraphy.


Subject(s)
Cholecystokinin/metabolism , Dietary Fats , Gallbladder/diagnostic imaging , Gallbladder/metabolism , Administration, Oral , Adult , Dietary Fats/administration & dosage , Dietary Supplements , Female , Gallbladder/drug effects , Gallbladder/physiology , Gallbladder Emptying/drug effects , Gallbladder Emptying/physiology , Humans , Lactose/administration & dosage , Male , Metabolic Clearance Rate , Middle Aged , Radionuclide Imaging/methods , Radionuclide Imaging/standards , Radiopharmaceuticals/pharmacokinetics , Reference Values
19.
Arch Pediatr Adolesc Med ; 157(3): 249-55, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12622674

ABSTRACT

OBJECTIVES: To investigate the barriers to highly active antiretrovial therapy (HAART) adherence among human immunodeficiency virus (HIV)-infected adolescents and to explore the association of barriers and nonadherence. DESIGN: Structured interviews were conducted to determine the barriers associated with adherence; principal component factor analysis was performed on scores of the 19 barrier variables. SETTING: Human immunodeficiency virus-infected adolescents were recruited from 13 US cities into the REACH (Reaching for Excellence in Adolescent Care and Health) Project, the first large-scale disease progression study of HIV-positive adolescents infected through sexual behavior or injection drug use. PATIENTS: Human immunodeficiency virus-infected adolescents in the REACH cohort who were prescribed HAART (N = 114) were included in the analyses. MAIN OUTCOME MEASURES: The main outcome measures were self-report of adherence and barriers to adherence and viral load (HIV-1 RNA level in plasma). RESULTS: Viral load was significantly associated with self-report of adherence to HAART (P =.02). Only 28.3% of adolescents reported taking all of their prescribed antiretroviral medications in the previous month. Factor analysis of the barriers to adherence indicates there are 2 factors accounting for the largest proportion of the variance: (1) medication-related adverse effects (both physical and psychological) and (2) complications in day-to-day routines. CONCLUSIONS: Adherence was tied closely with daily routine, which supports the assumption that working closely with adolescents to improve their organizational skills may be necessary to improve adherence. Patient-level intervention, provider-level intervention, and health care system modification may all be necessary to improve HIV-infected adolescents' adherence to HAART.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , Treatment Refusal/statistics & numerical data , Adolescent , Female , HIV-1/isolation & purification , Humans , Male , RNA, Viral/blood , Treatment Refusal/psychology , United States , Viral Load
20.
Drug Alcohol Depend ; 67(3): 227-34, 2002 Aug 01.
Article in English | MEDLINE | ID: mdl-12127193

ABSTRACT

Little is known about the impact of sexual or physical abuse history on response to alcohol treatment. This prospective study investigated the relationships between sexual and physical abuse histories, participants' characteristics, and response to inpatient alcohol treatment. Forty-one women and 59 men were assessed monthly for 1 year following hospitalization for alcohol dependence. Survival analyses showed that sexual abuse history was associated with shorter times to first drink and relapse. Physical abuse history was not associated with poorer drinking outcomes. Although women were more likely than men to have a history of sexual abuse, no gender differences were found in drinking outcomes. Poorer drinking outcomes were found among participants who at baseline were not married, had less than a college education, were not employed full time, or carried a diagnosis of depression or other psychiatric disorder. When adjusted for these characteristics, the associations between sexual abuse history and times to first drink and relapse were no longer statistically significant. While sexual abuse history is a clinically meaningful predictor of return to drinking we note the importance of considering patients' background and clinical characteristics in examining the impact of sexual abuse history on drinking outcomes following treatment.


Subject(s)
Alcoholism/therapy , Domestic Violence , Hospitalization , Sex Offenses , Adult , Alcoholism/epidemiology , Alcoholism/psychology , Chi-Square Distribution , Confidence Intervals , Domestic Violence/psychology , Domestic Violence/statistics & numerical data , Female , Hospitalization/statistics & numerical data , Humans , Male , Middle Aged , Multivariate Analysis , Proportional Hazards Models , Prospective Studies , Sex Offenses/psychology , Sex Offenses/statistics & numerical data , Treatment Outcome
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