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A longitudinal analysis of factors associated with morbidity in cocaine abusers with psychiatric illness.

We conducted a study to characterize a population of cocaine users who were referred to a state psychiatric institution, identify treatment problems including reasons for relapse, and develop strategies to improve treatment outcome. Using a data base system from a tertiary-care hospital emergency department, we identified a sample of 80 patients with a cocaine-related presentation who came to the emergency department and were referred to the psychiatric facility. Forty-six percent had consumed crack cocaine, and 65% reported ingesting cocaine with other drugs, half of them with alcohol. Suicidal ideation or attempt was the most common reason for referral. A retrospective review of 58 of the 80 referrals to the psychiatric facility showed that over half of the patients were given a concurrent psychiatric diagnosis and required hospitalization on an acute-care psychiatric unit. Sixty-two percent of those admitted had prior hospitalizations at the psychiatric facility, yet only five patients had received treatment for substance abuse. Seventy-four percent were readmitted to the psychiatric facility within 1 year of their index episode, with a higher rate of relapse among persons with dual diagnoses compared to cocaine users without dual diagnoses (p less than 0.05). Possible reasons for relapse included lack of referral for substance abuse treatment, nonintegrated treatment of psychiatric illness and substance abuse, lack of psychosocial support, and unresolved financial or job-related stressors. The data support increased funding to facilities that treat persons with dual diagnoses, and suggest the need to develop comprehensive treatment approaches involving a multidisciplinary team to address issues of mental illness and substance abuse concomitantly, and to identify and resolve stressors leading to relapse.

Adult↗

Longitudinal analysis of Mycobacterium tuberculosis 19-kDa antigen-specific T cells in patients with pulmonary tuberculosis: association with disease activity and cross-reactivity to a peptide from HIVenv gp120.

CD8(+) T cells play a central role in immune protection against infection with Mycobacterium tuberculosis. One of the target epitopes for anti-M. tuberculosis directed CD8(+) T cells is the HLA-A2-restricted 19-kDa lipoprotein peptide VLTDGNPPEV. T cell clones directed against this epitope recognized not only the nominal peptide ligand, but also a closely related peptide (VPTDPNPPEV) from the HIV envelope gp120 (HIV(env) gp120) protein characterized by IFN-gamma release. This cross-reactivity was confirmed in ex vivo in M. tuberculosis 19-kDa tetramer-sorted T cells from patients with tuberculosis and in HIVgp120 tetramer-reactive T cells sorted from HIV(+) patients. M. tuberculosis 19-kDa antigen-reactive T cells were present in HLA-A2(+) patients (10/10) with HIV infection with no evidence of M. tuberculosis infection, but they are absent in peripheral blood lymphocytes from healthy HLA-A2(+) individuals (10/10). M. tuberculosis 19-kDa antigen-reactive T cells were elevated in acute pulmonary tuberculosis, declined with response to therapy (7/10 patients) and resided in the terminally differentiated CD8(+) T cell subset. CD8(+) cross-reactive T cells recognizing HIV(env) or M. tuberculosis 19-kDa antigens may contribute to pathogenesis in individuals co-infected with both pathogens and may also present a marker for active tuberculosis.

Antigens, Bacterial↗

Longitudinal analysis of adolescent growth of ladino and Mayan school children in Guatemala: effects of environment and sex.

The rate of growth in height and the timing of adolescent growth events are analyzed for two samples of Guatemalan children. One sample includes Mayan school children, 33 boys and 12 girls between the ages of 5.00 to 17.99 years, living under poor conditions for growth and development. The second sample includes ladino children, 78 boys and 85 girls of the same age range, living under favorable conditions for growth. The Preece-Baines model I function is used to estimate mean values for rates and timing of childhood and adolescent growth events for the two groups. Significant statistical contrasts (t-tests) of these means show Mayan boys reach the age of "take-off" (TO; the onset of the adolescent growth spurt) 1.45 years later, achieve peak height velocity (PHV) 1.68 years later, and continue growing for about 2.0 years longer than do the ladino boys. Despite the Mayan boys' increased duration for growth they grow significantly more slowly than the ladinos. Mayan boys are 6.60 cm shorter than ladinos at the age of TO and are estimated to be 7.71 cm shorter than the ladinos at adulthood. Mayan girls reach the age of TO 0.93 years later than do the ladina girls, but the two groups do not differ in the age at PHV or the age at adulthood. The mean height of Mayan girls is significantly less than that of ladinas at the age of TO (6.5 cm), and this difference increases to an estimated 11.14 cm at adulthood. Possible causes of these ethnic and sex-related differences in amounts and rates of growth are discussed in relation to hypotheses about the genetic and environmental determinants of human development.

Adolescent↗

Longitudinal analysis of the use of etanercept versus infliximab determined from medical chart audit.

OBJECTIVE: To describe the dosing of etanercept and infliximab for the treatment of rheumatoid arthritis (RA). METHODS: Adult patients with a diagnosis of RA who were treated with either etanercept or infliximab between 1999 and 2002 were selected from 16 rheumatology practices in the western and southeastern United States. Patients with a terminal illness or those receiving a tumor necrosis factor (TNF)-alpha inhibitor for an indication other than RA were excluded. Data were collected through a review of the patient medical records. Data collected on each patient included demographics, concurrent disease-modifying antirheumatic drug therapy, TNF-alpha inhibitor dose, frequency, duration of TNF-alpha inhibitor therapy, and discontinuation of TNF-alpha inhibitor therapy. RESULTS: A total of 244 patients were included in the evaluation (etanercept only [n=128; 52%], infliximab only [n=89; 36%], both [n=27; 11%]). The mean age of these patients was 55.1+/-13.3 years, 54.9+/-13.5 years, and 52.8+/-14.0 years, respectively; the mean duration of RA was 13.3 +/- 8.8 years, 13.4+/-8.0 years, and 14.0 +/- 9.9 years, respectively. Female patients constituted 70% of the sample. Health maintenance organization insurance was the most common form of medical insurance (45.8%), followed by Medicare (22.3%). The mean duration of follow-up for etanercept and infliximab treatment was 29.3+/-14.1 months and 14.8+/-6.9 months, respectively. Among patients who were still receiving therapy at the time of review, the mean initial and last etanercept doses were 25.0 mg versus 25.8 mg (P=0.16); the mean initial and last infliximab doses were 3.38 mg/kg versus 4.51 mg/kg (P<0.001). CONCLUSION: The dosing of etanercept and infliximab therapy was consistent with the approved labeling of both medications.

Antibodies, Monoclonal↗

The relationship between parental diagnosis, offspring temperament and offspring psychopathology: a longitudinal analysis.

BACKGROUND: The study examines the relationship between child temperament and a diagnosis of anxiety and/or depression as an adult and what influence parent psychopathology may have on the temperament-diagnosis relationship. METHODS: The sample consists of 151 offspring who were initially selected as being at high or low risk for major depression on the basis of the presence or absence of a lifetime history of MDD in their parents. The parents and offspring were independently interviewed with a modified version of the Schedule for Affective Disorders and Schizophrenia-Lifetime (Mannuzza et al., 1986) and completed a battery of instruments which included the Dimensions of Temperament Survey (Lerner et al., 1982). They were interviewed three times during the course of the study: Time 1, Time 2, and Time 10. RESULTS: There is a similar distribution of offspring disorders in the same parental diagnostic groups. There is a significant temperamental difference between the offspring of parents with a single disorder in comparison to offspring of parents with comorbid disorder. The former is characterized by significantly greater levels of adaptability/approachability. Low attention span at Time 1 is significantly predictive of an offspring lifetime diagnosis of major depression controlling for ADHD in comparison to offspring with neither disorder. Greater irritability, higher activity level and lower adaptability at Time 1 were significantly predictive of offspring lifetime diagnosis of comorbid disorder in comparison to the MDD only group. LIMITATIONS: This is a retrospective cohort study using a temperament measure from Time 1 versus lifetime diagnoses and consisting of a relatively small sample size for several of the diagnostic categories. CONCLUSIONS: There appears to be a link between parental psychopathology and offspring temperament. The data also provide further support for the notion that comorbid anxiety and depression disorder is a distinct entity in comparison to MDD only and new evidence that it may be predicted by a specific underlying temperament profile.

Adolescent↗

T-cell division in human immunodeficiency virus (HIV)-1 infection is mainly due to immune activation: a longitudinal analysis in patients before and during highly active antiretroviral therapy (HAART).

In human immunodeficiency virus (HIV)-1 infection, highly increased T-cell turnover was proposed to cause exhaustion of lymphocyte production and consequently development of AIDS. Here, we investigated cell proliferation, as measured by expression of the Ki-67 nuclear antigen, in peripheral blood CD4(+) and CD8(+) lymphocyte subpopulations before and during highly active antiretroviral therapy (HAART). In untreated HIV-1 infection, both the percentage and number of Ki-67(+) CD4(+) and CD8(+) lymphocytes were significantly increased, compared with values obtained from healthy individuals. A more than 10-fold increase in the percentage of dividing naive CD4(+) T cells in the blood was found when the number of these cells were below 100 per microL. HAART induced an immediate decline in Ki-67 antigen expression, despite often very low CD4(+) T-cell numbers, arguing against increased proliferation being a homeostatic response. After approximately 24 weeks of HAART treatment, a transient increase in the number of proliferating cells was seen, but only in the CD4(+) CD27(+) memory pool. In the CD8(+) T-cell compartment, the number of dividing cells was elevated 20- to 25-fold. This increase was most notable in the CD27(+) CD 45RO(+) and CD27(-) CD45RO(+) memory CD8(+) T-cell pool, corresponding with the degree of expansion of these subsets. Reduction of plasma HIV-RNA load by HAART was accompanied by a decrease in numbers and percentages of dividing cells in all CD8(+) T-cell subsets. Taken together, our results indicate that peripheral T-cell proliferation is a consequence of generalized immune activation. (Blood. 2000;95:249-255)

Anti-HIV Agents↗

Longitudinal analysis of serum cytokine concentrations in systemic sclerosis: association of interleukin 12 elevation with spontaneous regression of skin sclerosis.

OBJECTIVE: Skin sclerosis that progresses in the earlier disease phase in systemic sclerosis (SSc) spontaneously regresses thereafter. We investigated the relationship between changes of the serum cytokine profile and changes in skin fibrosis in patients with SSc. METHODS: Serum cytokine levels were examined by ELISA using 180 sera samples from 26 patients with early diffuse cutaneous SSc (dcSSc) with mean disease duration of 2.1 years. The mean followup period was 4.9 years (range 2-8). Cytokine mRNA expression in the affected skin was quantified by real-time reverse transcription-polymerase chain reaction. RESULTS: Modified Rodnan total skin thickness score decreased after 2, 4, and 6 years compared to that at first visit. Serum levels of the Th2 cytokines interleukin 6 (IL-6) and IL-10 and monocyte chemotactic protein-1 (MCP-1) were higher at first evaluation compared to healthy controls, while IL-4 levels were normal. Levels of all Th2 cytokines generally decreased as skin sclerosis regressed. Conversely, levels of serum IL-12, a Th1-inducing cytokine, were lower at first visit relative to controls, but increased by roughly 15-fold after 6 years to significantly higher levels than controls. Surviving dcSSc patients exhibited elevated IL-12 levels compared to deceased patients. Serum levels of transforming growth factor-ss1 (TGF-ss1), a fibrogenic cytokine, increased throughout followup, with slightly decreased levels at later timepoints. IL-12 mRNA expression was upregulated in affected skin from patients with late-stage dcSSc, while TGF-ss1 and MCP-1 expression was downregulated. CONCLUSION: These results suggest that a shift from Th2 to Th1 response correlates with improvement in skin fibrosis in SSc, and that IL-12 level is a serologically useful marker for disease activity and prognosis.

Adult↗

Longitudinal analysis of the effect of apolipoprotein E epsilon4 and education on cognitive performance in elderly subjects: the PAQUID study.

BACKGROUND: The apolipoprotein E (apoE) epsilon4 allele has been shown to be a risk factor for dementia, but it is not clear to what extent apoE affects overall cognitive function in non-demented elderly subjects, or how this risk may be modified by gene-environment interactions. OBJECTIVE: To examine changes in cognitive function in elderly people as a function of the apoE epsilon4 phenotype. METHODS: A community based prospective cohort study of 600 non-demented subjects aged over 65 years living in Gironde (France) was analysed to evaluate change over time (seven years) in scores on the mini-mental state examination (MMSE). RESULTS: Age at cohort inception was negatively associated with cognitive performance for both epsilon4 carriers and non-carriers (p < 0.001). The evolution of MMSE scores differed as a function of age: scores remained stable among younger subjects but decreased over time in older subjects. The epsilon4 allele was shown to be significantly associated with lower cognitive performance at baseline (p = 0.02). The course of cognitive performance during the follow up was the same for both epsilon4 carriers and non-carriers. Lower educational level was associated with lower cognitive performance at baseline (p < 0.001) and the effect of an epsilon4 allele on cognitive performance disappeared after adjustment for education. When incident cases of dementia were excluded, the results were unchanged except for the course of the MMSE scores, which now remained stable over time in the older subjects. CONCLUSIONS: apoE epsilon4 carriers show decreased MMSE scores compared with epsilon4 non-carriers, but the effect of apoE on cognition disappears after adjustment for education. Non-demented elderly people maintain a stable cognitive performance regardless of their apoE phenotype.

Aged↗

Health inequality and users' risk-taking: a longitudinal analysis in a French reproductive technology centre.

This article sets out to provide a demographic analysis of the production of social inequality through IVF trajectories in a reproductive technology centre of a French hospital. However specific this example may be, it reveals one of the paradoxes of social inequalities in health: lay experience of risk in reproductive technology shows profound inequalities related to social status, despite the fact that equality would seem to be guaranteed in France, since the social security system covers the full cost of the treatments. We will try to understand this paradox through a lifecourse approach. Thus, it will be shown that social inequality in reproductive health is deeply rooted in social scenarios of infertility that lead to differentiated medical experience: there is little benefit and even a worsening in the situation of lower class women, who were faced with unpredictable risks related to the collective testing of these new technologies. Conversely, the possibility of inventing new lifestories, which may or may not include motherhood, was given to upper class women who take calculated risks to delay the scheduling of their pregnancies. In short, this study confirms that the production of social inequality in reproductive health can only be understood in connection with the social dynamics of lifestyles, resulting in specific medical patterns. This paper also leads to the assumption that these social scenarios are related to attempts to enhance the different forms of capital: economic, cultural and social capital. In addition, the presence of risks aggravates this inequality process. This raises another question: do reproductive technologies result in reinforcing social inequality?

Adult↗

Meal programs improve nutritional risk: a longitudinal analysis of community-living seniors.

OBJECTIVE: To determine the independent association of meal programs (eg, Meals On Wheels and other meal programs with a social component) and shopping help on seniors' nutritional risk. DESIGN: Cohort design. Baseline data were collected with an in-person interview and subjects were followed up for 18 months via telephone interview. SUBJECTS/SETTING: Cognitively well, vulnerable (ie, required informal or formal supports for activities of daily living) seniors were recruited through community service agencies in southwestern Ontario, Canada. Three hundred sixty-seven seniors participated in baseline interviews and 263 completed data collection at 18-month follow-up; 70% participated in meal programs at baseline. MAIN OUTCOME MEASURES: The 15-item Seniors in the Community: Risk Evaluation for Eating and Nutrition (SCREEN) questionnaire identified nutritional risk at 18 months. STATISTICAL ANALYSES PERFORMED: Descriptive and bivariate analyses were performed and significant associations (P<0.05) used to build the full multiple linear regression model. Meal and shopping variables were forced into the model as predictors of follow-up SCREEN questionnaire scores. RESULTS: Meals On Wheels use was independently associated with higher SCREEN questionnaire scores (ie, less risk), as was higher income. Baseline SCREEN questionnaire scores also strongly and positively predicted follow-up scores. Self-reported depression at baseline was associated with lower scores at follow-up. Although use of programs at baseline was associated with decreased risk, if participants experienced increased use of the program (eg, more meals) during the follow-up period this was associated with lower scores, or increased risk. CONCLUSIONS: Meal programs can improve or maintain nutritional risk for vulnerable seniors. Increased use of these programs over time may indicate a senior's declining status. Seniors who are in need of informal or formal supports for food shopping or preparation should be encouraged to participate in meal programs as a means of maintaining or improving their nutrition.

Activities of Daily Living↗

Longitudinal analysis of CD8 T-cell responses to HIV and hepatitis C virus in a cohort of co-infected haemophiliacs.

OBJECTIVE: To investigate CD8 T-cell responses to HIV and hepatitis C virus (HCV) over time in a group of co-infected children with haemophilia to assess the influence of the virus infections on each other and on clinical outcome. DESIGN: The HIV and HCV CD8 T-cell response of HLA-A2 co-infected individuals in the cohort were analysed at two time points, looking at the frequency and phenotype of HIV-specific T cells and assessing overall responses to the two viruses. METHODS: Peripheral blood mononuclear cells (PBMC) from 72 HLA-A2 co-infected individuals were analysed using an HIV HLA-A2 tetramer and by IFN-gamma ELISpot using a panel of HIV and HCV antigens. PBMC from a group of 26 HLA-A2 HIV mono-infected adults were also analysed as a comparison. RESULTS: We identified two distinct patterns of response: some patients had a limited response to either virus whilst others made responses to a range of HIV epitopes. HCV responses were detected only in those who made multiple responses to HIV epitopes (P<0.0001). HCV infection had an influence on the phenotype of HIV-specific CD8 T cells, with a reduction in relative perforin and CD57 expression. Lack of functional or tetramer-positive HIV-specific T cells was associated with a decline in absolute CD4 T-cell counts between the time points (up to 7 years; P = 0.005). CONCLUSION: HCV infection has an impact on the phenotype of HIV-specific CD8 T cells. In this well-defined cohort, failure to maintain effective CD8 T-cell responses against HIV may contribute to disease progression.

Adolescent↗

The effect of new and continuing prescription drug use on cost: a longitudinal analysis of chronic and seasonal utilization.

OBJECTIVE: To provide basic information about 2 factors contributing to rising prescription drug costs--utilization trends and product selection. BACKGROUND: Prescription drug costs have risen sharply in recent years, and continued growth is expected. There is little consensus about appropriate cost-management strategies, in part because quantitative data on the causes and implications of increased drug costs are lacking. METHODS: This study followed 463,820 continuously enrolled adult (> or = 18 years of age on January 1, 1996) utilizers of 15 chronic or seasonal therapeutic classes for 2.5 years (January 1996 through June 1998) using a pharmacy benefit manager's multiple-payer claims database. Outcome measures included (1) change in utilization rate, (2) relationship between new use and utilization growth, (3) stability of the treated population (ie, mostly long-term use vs high rates of turnover), and (4) product mix changes (ie, cost per dispensed day for 1996 vs 1997 and for new vs continuing users, controlling for inflation). RESULTS: Of the 463,820 utilizers, 97% were commercially insured and 3% enrolled in Medicare risk plans; 40% were enrolled in managed care and the remainder covered by indemnity insurance. Rates of growth and turnover varied substantially by class. The highest 2-year utilization rate change was 66.7% for antihyperlipidemic agents; change was < 10% in only 3 classes. Across classes, an average of 38.7% of 1997 users were new (ie, no use in 1996) and an average of 34.0% of 1996 users were dropouts (ie, no use in 1997). Utilization growth depended heavily on treatment continuation; classes with high dropout rates (eg, antirheumatic, antiasthmatic) did not have high growth rates, even with high rates of new use. In most classes, costs were not higher for new than for continuing users. In some classes, however (eg, antipsychotic, antidiabetic), both new and continuing users increased their use of newer, more expensive products. CONCLUSIONS: Because factors underlying rising prescription drug costs vary by therapeutic class, cost-containment strategies should address these differences. Further research is needed to assess the clinical and economic costs and benefits of rapid growth in the utilization of certain therapeutic classes.

Adult↗

A longitudinal analysis from bite-wing radiographs of the rate of progression of approximal carious lesions through human dental enamel.

Four to ten years of serial bite-wing radiographs from over 700 children from five groups, three in Sweden and two in the U.S., were interpreted. By analysing changes in the depth of unfilled lesions over time, the mean time and probability distribution for the time a lesion remains in both the outer half and inner half of the enamel were estimated. The procedure incorporated information on filled lesions and non-progressing lesions and thus minimized bias that results in overestimation of the progression rate. In primary teeth, in both the U.S. and Swedish groups, it took on average 12 months for a lesion to progress through the outer half of the enamel and on average 10-12 months for a lesion to progress through the inner half. In newly-erupted first permanent molars, it took 21-23 months for a lesion to progress through the outer half of the enamel and between 19 (U.S. data) and 28 months (Swedish data) for progression through the inner half. In older adolescents in the two Swedish groups, progression was slower: 38-41 months through the outer-half and 47-56 months through the inner-half. In older U.S. adolescents, progression appeared to be more rapid: 16 months through the outer half of the enamel and 27 months through the inner half. The duration of time a lesion remains in different halves of the enamel could be approximated by a piecewise exponential or exponential probability distribution, which exhibits extreme variability. Assuming duration in each half of the enamel follows an exponential distribution with a mean of 2 yr, about 10 per cent of new lesions will progress through the enamel in one year and 25 per cent in two years. However, over 40 per cent of the lesions will not have progressed in 4 yr. There were no consistent differences in the rate of progression by sex, between upper and lower dentitions, for premolars versus molars, or between high and low-risk individuals.

Adolescent↗

Longitudinal analysis of high-risk HPV infections reveals within-host viral genome changes over time.

Persistent infection with high-risk (HR)-HPV causes cervical cancer, however, it is unclear why most infections resolve while a minority progress. We deep sequenced the HPV genomes of 1,228 HR-HPV-positive serial samples from 351 women with persistent infections (2-10 serial samples per woman over 1-8 years), including 279 controls and 72 precancer/cancer cases, to assess HR-HPV genome changes during infection and relation to infection outcomes. Seventy-seven percent of persistent infections (45-97% by HPV type) were infections with the same exact viral genome isolate; for HPV16, only 52% were persistent with the same isolate. This may suggest some infections include a type-specific isolate switch or new isolate infection during persistence. We additionally observed within-host change to the HPV genome estimated as gradual changes to intrahost single nucleotide variant (iSNV) frequency, and changes varied by HPV type, with HPV33 infections showing the most iSNV changes. Cases exhibited fewer viral genome changes during infection compared to controls (OR = 0.31, 95% CI&#x2009;=&#x2009;0.1 - 0.86, p&#x2009;=&#x2009;0.019), suggesting a more stable and clonal viral genome in cases. By viral gene, E7 had fewer nonsynonymous mutations in the cases compared to controls that cleared within 2 years of infection (p&#x2009;=&#x2009;0.012), which confirms the importance of E7 conservation and suggests mutations to E7 reduce persistence associated with progression. There was a similar pattern in E4 (p&#x2009;=&#x2009;0.013), while E5 had more changes in the cases (p&#x2009;=&#x2009;0.008). A subset of 28 infections had an intervening HPV-negative sample between HPV-positive visits; 93% of these infections had the same exact viral genome isolate in the samples before and after the negative, consistent with subclinical persistence and subsequent re-detection. Our data suggests that HR-HPV type-persistence can include a collection of viral isolates, and viral mutations during infection, particularly in E7, reduce HR-HPV persistence and thus carcinogenic potential.

Humans↗

Longitudinal analysis of clinical markers following antiretroviral therapy initiated during acute or early HIV type 1 infection.

BACKGROUND: Treatment of acute human immunodeficiency virus type 1 (HIV-1) infection may have unique immunologic, virological, and clinical benefits. However, the timing of treatment, optimal starting regimens, and expected response to therapy have not been defined.Methods. One hundred two subjects treated during acute and early HIV-1 infection were observed prospectively to determine the effect of time elapsed before initiation of therapy on time to virological suppression and absolute CD4+ cell count. Subjects were divided into pre- and postseroconversion groups on the basis of HIV-1 antibody status at the time of initiation of treatment. Absolute CD4+ cell counts were compared between these groups and with those of historical untreated persons who had experienced seroconversion. Potential predictors of time to virological suppression and CD4+ cell count at > or =12 months were assessed. RESULTS: Ninety-nine (97%) of 102 subjects achieved virological suppression. The median time to suppression was 11.1 weeks (95% confidence interval, 9.4-14.9) and was independent of initial regimen. The mean CD4+ cell count at 12 months was 702 cells/mm3 (95% confidence interval, 654-750 cells/mm3) and showed an increasing trend over 60 months. Treated subjects demonstrated a statistically significant gain in the CD4+ cell count, compared with untreated historical control subjects, at > or =12 months. Comparable virological and immunologic outcomes were seen in the pre- and postseroconversion groups. Baseline virus load and nadir CD4+ cell count predicted time to virological suppression and CD4+ cell count at > or =12 months, respectively. CONCLUSIONS: Early treatment of HIV-1 infection is well tolerated and results in rapid and sustained virological suppression. Preservation of CD4+ cell counts may be achieved with early therapy, independent of seroconversion status. Protease inhibitor-based and nonnucleoside reverse-transcriptase inhibitor-based regimens show comparable performance in tolerability, time to virological suppression, and CD4+ cell count when used as a first regimen.

Acquired Immunodeficiency Syndrome↗

A longitudinal analysis of maternal serum insulin-like growth factor I (IGF-I) and total and nonphosphorylated IGF-binding protein-1 in human pregnancies complicated by intrauterine growth restriction.

In cord blood and late gestation maternal serum, IGF-I is positively correlated with birth weight, whereas IGF-binding protein-1 (IGFBP-1) is inversely correlated with birth weight. Our goal was to determine whether maternal serum or amniotic fluid concentrations of IGF-I, IGFBP-1, or nonphosphorylated IGFBP-1 (npIGFBP-1) in early gestation predict later fetal growth abnormalities. Maternal serum was collected prospectively across gestation (5-40 wk) from 749 pregnant subjects. Amniotic fluid was collected after amniocentesis during wk 15-26 from 207 subjects. We compared median serum concentrations of IGF-I, IGFBP-1, and npIGFBP-1 in 38 subjects who delivered growth-restricted infants with the control group of 236 subjects with normal weight infants for each gestational age grouping, wk 5-12, 13-23, and 24-34. In the control group median IGF-I concentrations were 14.8, 11, and 15.6 nmol/liter for wk 5-12, 13-23, and 24-34, respectively, compared with 13.7, 14.3, and 10.6 nmol/liter in the intrauterine growth restriction (IUGR) group. Median IGFBP-1 concentrations were 8.5, 30.4, and 24.4 nmol/liter, respectively, in controls, compared with 11.4, 28.6, and 25.5 nmol/liter in the IUGR group. Median npIGFBP-1 concentrations were 6.9, 22, and 17.4 nmol/liter, respectively, in controls, compared with 5.0, 32.1, and 24.2 nmol/liter in the IUGR group. In the control group the median amniotic fluid IGFBP-1 level was 13,160 nmol/liter, and the median npIGFBP-1 level was 15,970 nmol/liter; in the IUGR group these levels were 13,440 and 18,440 nmol/liter, respectively. No clinically useful differences were found between the IUGR and control groups. Our results do not support the use of maternal serum IGF-I or IGFBP-1 or amniotic fluid IGFBP-1 or npIGFBP-1 early in gestation to predict later fetal growth restriction.

Amniotic Fluid↗

Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis.

OBJECTIVE: To examine serial changes in serum anti-topoisomerase I (anti-topo I) antibody levels in patients with systemic sclerosis (SSc), as well as associations with clinical features and the in vivo activation status of circulating topo I-reactive T and B cells. METHODS: Serum anti-topo I antibody levels were serially measured at different time points in 28 SSc patients who were positive for anti-topo I antibody at their first visit (range of followup 6-29 years). The patients were subgrouped according to the disappearance (group 1) or persistence (group 2) of anti-topo I antibody. Clinical findings as well as T and B cell responses to topo I were compared between these 2 groups. RESULTS: Serum anti-topo I antibody disappeared during the period of followup in 6 patients (group 1), but persisted in 22 patients (group 2). Loss of anti-topo I antibody occurred within 10 years after the first visit and independently of treatment. Group 1 patients had less extensive skin and lung involvement and better survival rates than did group 2 patients. Complete loss of anti-topo I antibody followed a reduction in isotype expression and epitope reactivities. The kinetics of in vitro T cell proliferation induced by topo I were delayed and circulating topo I-reactive T cells were less frequently detected in group 1 versus group 2 patients, suggesting that the disappearance of anti-topo I antibody was due to loss of activation of topo I-reactive T cells. In vitro production of anti-topo I antibody in peripheral blood mononuclear cell cultures in response to antigenic stimulation in both group 1 and group 2 patients indicated persistence of anti-topo I antibody-producing "memory" B cells even after the loss of serum anti-topo I antibody. CONCLUSION: Our results indicate that there is a distinct subset of anti-topo I-positive SSc patients who lose anti-topo I antibody during the disease course and have a favorable outcome. In vivo production of anti-topo I autoantibody may require antigenic stimulation that activates topo I-reactive T and B cells.

Antibody Formation↗

Hospitalizations for critically ill children with traumatic brain injuries: a longitudinal analysis.

OBJECTIVE: This study examines the incidence, utilization of procedures, and outcomes for critically ill children hospitalized with traumatic brain injury over the period 1988-1999 to describe the benefits of improved treatment. DESIGN: Retrospective analysis of hospital discharges was conducted using data from the Health Care Cost and Utilization Project Nationwide Inpatient Sample that approximates a 20% sample of U.S. acute care hospitals. SETTING: Hospital inpatient stays from all types of U.S. community hospitals. PARTICIPANTS: The study sample included all children aged 0-21 with a primary or secondary ICD-9-CM diagnosis code for traumatic brain injury and a procedure code for either endotracheal intubation or mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Deaths occurring during hospitalization were used to calculate mortality rates. Use of intracranial pressure monitoring and surgical openings of the skull were investigated as markers for the aggressiveness of treatment. Patients were further classified by insurance status, household income, and hospital characteristics. Over the 12-yr study period, mortality rates decreased 8 percentage points whereas utilization of intracranial pressure monitoring increased by 11 percentage points. The trend toward more aggressive management of traumatic brain injury corresponded with improved hospital outcomes over time. Lack of insurance was associated with vastly worse outcomes. An estimated 6,437 children survived their traumatic brain injury hospitalization because of improved treatment, and 1,418 children died because of increased mortality risk associated with being uninsured. Improved treatment was valued at approximately dollar 17 billion, whereas acute care hospitalization costs increased by dollar 1.5 billion (in constant 2000 dollars). Increased mortality in uninsured children was associated with a dollar 3.76 billion loss in economic benefits. CONCLUSIONS: More aggressive management of pediatric traumatic brain injury appears to have contributed to reduced mortality rates over time and saved thousands of lives. Additional lives could be saved if mortality rates could be equalized between insured and uninsured children.

Adolescent↗