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Analysis of chicken TLR4, CD28, MIF, MD-2, and LITAF genes in a Salmonella enteritidis resource population.

Salmonella enteritidis is a foodborne pathogen that negatively affects both animal and human health. Genetic variations in response to pathogenic SE colonization or to SE vaccination were measured in a chicken resource population. Outbred broiler sires and 3 diverse, highly inbred dam lines produced 508 F1 progeny that were evaluated for either bacterial colonization after pathogenic SE inoculation or circulating antibody level after SE vaccination. Five candidate genes were selected for study, based on their biological function as possibly affecting response to SE: toll-like receptor 4 (TLR4), T-cell specific surface protein (CD28), macrophage migration inhibitory factor (MIF), MD-2, and lipopolysaccharide-induced tumor necrosis factor (TNF)-alpha factor (LITAF). Gene fragments were sequenced from the founder lines of the resource population. The LITAF and MIF genes were homozygous for all sires. Single nucleotide polymorphisms (SNP) were identified in 3 genes (TLR4, CD28, and MD-2) and were used to test for associations of sire SNP with SE response. Linear mixed models were used for statistical analyses. The CD28 broiler sire SNP was associated with both bacterial load in the cecum (P < 0.003) and vaccine antibody response (P < 0.05). The MD-2 SNP was associated (P < 0.04) with the bacterial load in the spleen. The use of these SNP in these genes in marker-assisted selection may result in enhancement of disease resistance.

Animals↗

Circadian patterns of sleep, sleepiness, and performance in older and younger adults.

STUDY OBJECTIVE: To compare circadian patterns of sleep, subjective sleepiness, and psychomotor performance in older and younger adults. DESIGN: Controlled experimental laboratory study. SETTING: General Clinical Research Center. PARTICIPANTS: Healthy older adults (n = 17, mean age 76 years) and healthy younger adults (n = 19, mean age 23 years). INTERVENTIONS: Subjects lived for 60 consecutive hours on a 90-minute sleep-wake cycle (30 minutes in bed, 60 minutes awake). Electroencephalographic recordings were conducted during bedrest periods. Self-ratings and psychomotor performance tests were conducted during 60-minute wake periods. MEASUREMENTS AND RESULTS: Data were analyzed with cosinor and linear mixed models. Amplitude and phase of the core body temperature rhythm did not significantly differ by age group. Older adults had significantly reduced mean levels and amplitude of rhythms in total sleep time and sleep efficiency and increased mean levels and amplitude of rhythms in sleep latency and wake after sleep onset. Age groups did not differ in mean level of subjective sleepiness, but older adults had reduced amplitude. Older adults had worse overall psychomotor performance, with evidence of larger circadian amplitude in some of these rhythms. Age groups did not differ on the phase position of any rhythm. CONCLUSIONS: Older adults had a lower level and smaller circadian variation of sleep propensity compared with younger adults, whereas wakefulness and psychomotor performance rhythms tended to show increased circadian variation among older subjects. These findings likely result from a combination of age-related changes in cortical function, homeostatic sleep mechanisms, and circadian regulation.

Adult↗

Methods for combining phenological time series: application to bud burst in birch (Betula pendula) in Central Finland for the period 1896-1955.

We compared four methods for combining separate fragmentary phenological time series into a single long reliable series. The systematic linear effect of differences in observers, genotypes, geography and climate at the observation points produces disturbing variation in the observations and bias in the means of some time points. The three methods based on the adjustment of individual series eliminated the disturbing variation and bias. The methods were compared based on phenological observations of bud burst in birch (Betula pendula Roth). The method based on a linear mixed model of analysis of variance and the maximum likelihood estimation was considered preferable to the other methods.

Journal Article↗

Regeneration patterns in boreal Scots pine glades linked to cold-induced photoinhibition.

Regeneration patterns of Pinus sylvestris L. juveniles in central Siberian glades were studied in relation to cold-induced photoinhibition. Spatial distribution of seedlings in different height classes revealed higher seedling densities beneath the canopy than beyond the canopy, and significantly higher densities of seedlings < 50 cm tall on the north side of the trees. These patterns coincided with differences in light conditions. Compared with plants on the north side of canopy trees (north-exposed), photosynthetic photon flux (PPF) received by plants on the south side of canopy trees (south-exposed) was always higher, making south-exposed plants more susceptible to photoinhibition, especially on cool mornings. Chlorophyll fluorescence data revealed lower photochemical efficiency and increased non-photochemical quenching of small (20-50 cm in height), south-exposed seedlings from spring to early autumn, indicating increased excitation pressure on photosynthesis. Maximum rate of oxygen evolution was less in south-exposed plants than in north-exposed plants. Increased pools of xanthophyll cycle pigments and formation of the photoprotective zeaxanthin provided further evidence for the higher susceptibility to photoinhibition of south-exposed seedlings. A linear mixed model analysis explained many of the physiological differences observed in seedlings according to height class and aspect with early morning temperature and PPF as predictors. The link between photoinhibition and differential distribution of seedlings by height class suggests that photoinhibition, together with other environmental stresses, decreases the survival of small, south-exposed P. sylvestris seedlings, thereby significantly affecting the regeneration pattern of central Siberian pine glades.

Chlorophyll↗

Leaf and wood carbon isotope ratios, specific leaf areas and wood growth of Eucalyptus species across a rainfall gradient in Australia.

Leaves and samples of recent wood of Eucalyptus species were collected along a rainfall gradient parallel to the coast of Western Australia between Perth in the north and Walpole in the south and along a southwest to northeast transect from Walpole in southwestern Australia, to near Mount Olga in central Australia. The collection included 65 species of Eucalyptus sampled at 73 sites and many of the species were collected at several sites along the rainfall gradient. Specific leaf area (SLA) and isotopic ratio of 13C to 12C (delta 13C) of leaves that grew in 2002, and tree ring growth and delta 13C of individual cell layers of the wood were measured. Rainfall data were obtained from the Australian Bureau of Meteorology for 29 locations that represented one or a few closely located collection sites. Site-averaged data and species-specific values of delta 13C decreased with decreasing annual rainfall between 1200 and 300 mm at a rate of 1.63 per thousand per 1000 mm decrease in rainfall. Responses became variable in the low rainfall region (< 300 mm), with some species showing decreasing delta 13C with rainfall, whereas delta 13C increased or remained constant in other species. The range of delta 13C values in the low rainfall region was as large as the range observed at sites receiving > 300 mm of annual rainfall. Specific leaf area varied between 2 and 6 m2 kg(-1) and tended to increase with decreasing annual rainfall in some species, but not all, whereas delta 13C decreased with SLA. The relationship between delta 13C and SLA was highly species and soil-type specific. Leaf-area-based nitrogen (N) content varied between 2 and almost 6 g m(-2) and decreased with rainfall. Thus, thicker leaves were associated with higher N content and this compensated for the effect of drought on delta 13C. Nitrogen content was also related to soil type and species identity. Based on a linear mixed model, statistical analysis of the whole data set showed that 27% of the variation in delta 13C was associated with changes in SLA, 16% with soil type and only 1% with rainfall. Additionally, 21% was associated with species identity. For a subset of sites with > 300 mm rainfall, 43% of the variation was explained by SLA, 13% by soil type and only 3% by rainfall. The species effect decreased to 9% because there were fewer species in the subset of sites. The small effect of rainfall on delta 13C was further supported by a path analysis that yielded a standardized path coefficient of 0.38 for the effect of rainfall on SLA and -0.50 for the effect of SLA on delta 13C, but an insignificantly low standardized path coefficient of -0.05 for the direct effect of rainfall on delta 13C. Thus, in contrast to our hypothesis that delta 13C decreases with rainfall independent of soil type and species, we detected no statistically significant relationship between rainfall and delta 13C in leaves of trees growing at sites receiving < 300 mm of rainfall annually. Rainfall affected delta 13C indirectly through soil type (a surrogate for water-holding capacity) across the rainfall gradient. Annual tree rings are not clearly visible in evergreen Eucalyptus species, even in the seasonally cool climate of SW Australia. Generally, visible density transitions in the wood are related not to a strict annual cycle but to periods of growth associated mainly with rainfall. The relationship between delta 13C of leaves and the width of these stem increments was not statistically significant. Analysis of stem growth periods showed that delta 13C in wood responded to rainfall events, but carbohydrate storage and reallocation also affected the isotopic signature. Although delta 13C in wood of any one species varied over a range of 2 to 4 per thousand, there was a general relationship between delta 13C of the leaves and the annual range of delta 13C in wood. We conclude that species-specific traits are important in understanding the response of Eucalyptus to rainfall and that the diversity of the genus may reflect its response to the large climatic gradient in Australia and to the large annual and interannual variations in rainfall at any one location.

Australia↗

Effects of prenatal cocaine/polydrug use on maternal-infant feeding interactions during the first year of life.

The effects of prenatal cocaine use on quality of maternal-infant interactions were evaluated using the Nursing Child Assessment Feeding Scale (NCAFS). A total of 341 (155 cocaine using; 186 non-cocaine using) low socioeconomic, primarily African-American dyads were evaluated longitudinally at birth, 6.5, and 12 months. Group differences over time were examined, controlling for covariates, using a mixed-model linear approach. Women who used cocaine during pregnancy were less sensitive to their infants than non-cocaine-using women at 6.5 and 12 months. At 6.5 months, heavier prenatal cocaine users were less responsive to their infants than lighter users. In infants, prenatal cocaine exposure was related to poorer clarity of cues. There were no significant cocaine effects on maternal social-emotional growth fostering, cognitive growth fostering, or infant responsiveness to mother. Controlling for covariates, concentration of cocaine metabolites predicted maternal sensitivity to infant cues and infant clarity of cues at 1 year. Maternal cocaine use during pregnancy and other pre- and postnatal factors adversely affect maternal-infant interactions during the first year of life.

Black People↗

Impact of Helicobacter pylori infection on growth of children: a prospective cohort study.

OBJECTIVE: The aim of this study was to prospectively follow a cohort of children without Helicobacter pylori infection and to compare growth velocity in the children who become infected during follow-up with that of children who remained infection-free. METHODS: Three hundred forty-seven children in general good health, aged 12 to 60 months, who tested negative for H. pylori by the 13C-urea breath test, from three daycare centers in a lower-middle class borough of Cali, Colombia, were monitored for 2.5 years. Anthropometric measurements were performed every 2 months and breath tests every 4 months. Linear mixed models were used to analyze growth velocity in relation to onset of H. pylori infection. RESULTS: One hundred five (30.3%) children who were uninfected at the start of the study became infected during follow-up. Growth velocity in infected children was reduced by 0.042 +/- 0.014 cm/mo (P = 0.003) (approximately 0.5 cm/yr) after adjusting for age. The rate of deceleration in growth velocity was relatively constant over time. CONCLUSIONS: Among these lower-middle class children aged 12 to 60 months from a population with high prevalence of H. pylori infection, a new and sustained infection was followed by significant growth retardation.

Body Height↗

Consistency of swimming performance within and between competitions.

PURPOSE: The consistency of performance between events impacts how athletes should specialize in events, how competitions should be structured, and how changes in performance affect an athlete's placing in an event. We have therefore determined the consistency of swimming performance in events within and between two national-level competitions. METHODS: We used mixed linear modeling to analyze official performance times of 149 male and 162 female swimmers at a junior national championship, and of 117 male and 104 female swimmers at an open national championship 20 d later. The events differed in stroke (backstroke, breaststroke, butterfly, freestyle, and individual medley) or distance (50-1500 m). RESULTS: Swimmers were most consistent in their performance for the same event between the two competitions (typical variation between competitions, 1.4%; 95% likely range of true value, 1.3-1.5%). They were less consistent between distances of a given stroke within each competition (1.7%; 1.5-1.9%) and least consistent between strokes for a given distance (2.7%; 2.3-3.1%). Variation in performance between the longest continuous freestyle distances (400, 800, and 1500 m) in the open competition was half that between widely spaced freestyle distances (50, 200, and 800 m). Faster swimmers were more consistent (1.1%; 0.9-1.4%) for the same event between competitions than slower swimmers (1.5%; 1.3-1.9%). CONCLUSIONS: (a) Swimmers are stroke specialists rather than distance specialists; with the present set of events in competitions, they should concentrate training and competing on a particular stroke rather than a particular distance. (b) More swimmers would have a chance of winning a medal if events of a given stroke differed more widely in distance. (c) Factors that affect performance time by as little as 0.5% will affect the placing of a top junior swimmer.

Adolescent↗

A review and reanalysis of Bruno Schulz's "Erkrankungsalter schizophrener Eltern und Kinder [Age at onset of illness in schizophrenic parents and offspring]:" Zeitschrift für die gesamte Neurologie und Psychiatrie, 168, 709-721, 1940.

Nearly all previous evidence of the familial transmission of age at onset of schizophrenia has been in siblings and twins. In his paper, Bruno Schulz examined the age at onset distribution of schizophrenia in affected parent and offspring pairs, using a systematic series of ascertained cases (n = 106), as well as a second series of chronic in-patients (n = 36). The parent-offspring correlation in age at onset, for cases with a definite diagnosis in the systematically ascertained series, was estimated at 0.346 (95% confidence interval 0.134, 0.528). Schulz did not test for differences between the two series and between males and females, but our reanalysis, using correlational methods and a mixed linear model, did not detect any significant differences. These results are consistent with previous findings that age at onset of schizophrenia is influenced by familial factors which may be genetic.

Adult↗

Improvement of anemia among HIV-infected injection drug users receiving highly active antiretroviral therapy.

Although anemia is common during HIV infection, it is unclear whether potent antiretroviral therapy would improve or worsen anemia. We conducted a study to examine the impact of highly active antiretroviral therapy (HAART) on anemia in a cohort of HIV-positive injection drug users (IDUs) in Baltimore, Maryland. At baseline, the overall prevalence of anemia was 40%. During mean follow-up of one year, among 102 subjects who received HAART, there was a mean increase in hemoglobin of 3.6 +/- 1.7 g/L (p =.0003) [corrected] and a mean decrease in log(10) plasma HIV load of 0.25 +/- 0.06 copies/ml (p <.0002) [corrected]. Among 103 control subjects who were not receiving antiretroviral medications, there was a mean decrease in hemoglobin of 4.2 +/- 1.1 g/L (p <.04) [corrected] and mean increase in log(10) plasma HIV load of 0.78 +/- 0.17 copies/ml (p <.0001) [corrected]. Multivariate analysis using mixed linear models showed that HAART was associated with an increase of hemoglobin of 0.223 g/L per month (p <.0001) after adjusting for body mass index, opportunistic infections, and gender. HAART was associated with an improvement in anemia, and potential mechanisms that may be involved include a reduction in opportunistic infections and the anemia of chronic disease and an improvement in nutritional status.

AIDS-Related Opportunistic Infections↗

Long-term hepatitis B virus dynamics in HIV-hepatitis B virus-co-infected patients treated with tenofovir disoproxil fumarate.

BACKGROUND: The long-term impact of tenofovir disoproxil fumarate (TDF) on hepatitis B virus (HBV) replication has not yet been studied in HIV-HBV-co-infected patients. METHODS: We conducted a prospective study of HBV-DNA decay kinetics in 28 HIV-HBV-co-infected patients treated by TDF. HBV dynamics were studied using mixed linear models, and baseline factors affecting them were analysed using Cox models. RESULTS: The HBV-DNA load declined by a mean of 4.6 log copies/ml during follow-up (mean 71 weeks), and fell below the detection limit (200 copies/ml) in 21 patients. Inhibition of viral replication by TDF was associated with a decrease in alanine aminotransferase levels (125 versus 68 IU, P < 0.05). HBV-DNA decay was biphasic, with an rapid fall followed by a gradual decline. Baseline factors associated with a steeper first slope in the HBV-DNA decrease were high HBV load, positive hepatitis B e antigen (HBeAg) and YMDD mutations. Baseline factors increasing the time to reach an HBV-DNA level less than 200 copies/ml were high HBV load (150 days when HBV-DNA < 10 log, 316 days when HBV-DNA > 10 log) and positive HBeAg. Previous exposure to lamivudine or TDF-lamivudine did not modify HBV-DNA decrease under therapy in this population with a high prevalence of YMDD mutations. CONCLUSION: The long-term decline in HBV DNA under TDF is biphasic and is primarily influenced by the initial HBV load. However, the clinical significance of such an association remains moderate, and TDF can be efficiently included in the highly active antiretroviral therapy regimen of HIV-HBV-co-infected patients, regardless of HBV strains and their degree of replication.

Adenine↗

Effect of long-cycle structured intermittent versus continuous HAART on quality of life in patients with chronic HIV infection.

OBJECTIVE: To examine the effect of repeated, long-cycle structured intermittent versus continuous HAART on health-related quality of life (HRQL) and symptom distress in patients with chronic HIV infection and plasma HIV RNA of less than 50 copies/ml. DESIGN: Prospective survey of adult patients (n = 46) enrolled in a randomized clinical trial evaluating intermittent versus continuous HAART on immunological and virologic parameters. Patients (n = 23) randomized to structured intermittent therapy received serial cycles of 4 weeks on/8 weeks off HAART. OUTCOME MEASURES: HRQL was measured by the physical and mental health summary scores of the Medical Outcomes Study HIV Health Survey (MOS-HIV). Symptom distress was measured by the Symptom Distress Scale. Patients completed initial questionnaires prior to randomization and at weeks 4, 12, and 40 of the trial via a touch screen computer in an outpatient clinic. RESULTS: Baseline demographic and clinical characteristics were equivalent in both treatment groups. Although the mental health summary score declined significantly over time for the structured intermittent group, linear mixed modeling ANOVA indicated no significant difference across time for MOS-HIV summary and Symptom Distress Scale scores between the two treatment arms. CONCLUSION: In this small sample, repeated long-cycle structured intermittent therapy may not provide HRQL or symptom distress advantage compared to continuous HAART in patients with chronic HIV infection over 10 months of treatment. Further research in a heterogenous chronic HIV population and longer follow-up period is warranted.

Adult↗

Association of outcomes with organizational characteristics of neonatal intensive care units.

OBJECTIVE: Health outcomes may be influenced by organizational and management characteristics. We hypothesized that neonatal intensive care unit managerial practices and organizational processes could affect outcomes of births 500-1499 g, and we assessed this in eight neonatal intensive care units. DESIGN: Multiple-center cohort. SETTING: Eight acute care neonatal intensive care units in Washington, DC. PATIENTS: Infants weighing 500-1499 g, born from October 1, 1994, to February 19, 1997, to a resident of Washington, DC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Outcomes included 28-day survival/death, bronchopulmonary dysplasia (BPD), periventricular/intraventricular hemorrhage or periventricular leukomalacia (PIVH/PVL), retinopathy of prematurity (ROP), length of hospital stay, and days of mechanical ventilation. Managerial practices and organizational processes were rated by nurses (n = 218), physicians (n = 73), and respiratory therapists (n = 77). Risk-adjusted logistic and linear mixed models were used to assess the association of outcomes with the caregiver ratings. A lower incidence of PIVH/PVL was associated with better overall scores (p =.0036) and better subscores for leadership (p <.0001), coordination (p =.047), and conflict resolution (p =.020). Better values of the respiratory therapists', nurses', and physicians' scores were associated with lower mortality rates (p =.045) and BPD (p =.0057), PIVH/PVL (p <.0001), and ROP (p =.049), respectively. In multivariate analysis, the joint effects of the professional groups' scores were associated with the incidence of PIVH/PVL (p =.0047); the nurses' scores were associated with lower incidence of PIVH/PVL (p =.0051). The association between the respiratory therapists' scores and lower mortality rate (p =.025) also remained significant in multivariate analysis. CONCLUSIONS: We found that the organizational processes and managerial practices as rated by healthcare professionals in neonatal intensive care units were associated with the development of mortality and chronic, severe morbidity. We did not identify specific processes or practices that accounted for our results.

Cohort Studies↗

Is sternal skin conductance monitoring a valid measure of hot flash intensity or distress?

OBJECTIVE: To examine the validity of using sternal skin conductance monitoring as a measure of hot flash intensity and hot flash distress. DESIGN: Descriptive, prospective, longitudinal data from the 2-week baseline of a larger hot flash intervention study; 73 breast cancer survivors with daily hot flashes wore a hot flash monitor and completed a hot flash diary during two 24-hour assessment periods that were separated in time by 1 week. RESULTS: Data consisted of 569 diary rated hot flashes; 46.9% had magnitude of less than 2.0 micromhos (insufficient to meet objective hot flash criterion) and 26.3% had magnitude of 0.0 micromho (no change in skin conductance). Results from mixed-linear modeling indicated that, although magnitude significantly predicted hot flash intensity and distress, effect sizes were very small: less than 2% when using all observations, and less than 1% when using only the subset meeting objective hot flash criteria. Even after adjusting for covariates that were associated with intensity or distress, magnitude explained very little variance in intensity or distress (<2.2%). Scatterplots and locally weighted smooth regression curves also revealed very little relationship between magnitude and either intensity or distress. CONCLUSIONS: Findings indicate that objective change in sternal skin conductance, an indicator of sweat gland activity, should not be used as a proxy measure of subjective hot flash intensity or distress. Future research should continue to subjectively measure hot flash intensity and distress when these are important outcome variables to consider.

Female↗

Immunologic changes during unplanned treatment interruptions of highly active antiretroviral therapy in children with human immunodeficiency virus type 1 infection.

BACKGROUND: There are few data on the decline of CD4 cells or percentage during unplanned treatment interruptions in HIV-infected children. METHODS: Data were analyzed on children undergoing interruptions of three or four drug antiretroviral therapy (HAART) in the United Kingdom and Irish Collaborative HIV Paediatric Study and from Sophia Children's Hospital, Rotterdam. Children were included if they had taken HAART continuously for 3 months or longer before interruption and stopped for at least 4 weeks. The effects of CD4 at treatment initiation and of age, CD4, HIV RNA and disease stage at interruption on the CD4 decline during interruption were explored with linear mixed models. RESULTS: Seventy-one children (median age, 7.0 years) had experienced 82 unplanned interruptions of median duration 4.1 (interquartile range, 2.3 to 7.6) months. HAART was restarted after 59 (72%) interruptions (17 with the same and 42 with a new regimen). In children restarting HAART, median CD4% increased toward preinterruption levels by 6 months, when 46% had HIV RNA <400 copies/ml (vs. 15% at interruption). The rate of CD4% decline in 51 children with a median of 3 (range, 2 to 10) CD4 measurements was 0.52% per month (6.2% annually); it was independent of age, CD4 at HAART, preinterruption CD4 or HIV RNA or previous AIDS. CONCLUSIONS: Although the average CD4 decline after stopping HAART appears similar to that in adults, large variability suggests that when designing pediatric trials of planned treatment interruptions, interruption length could be determined by time taken for CD4 to decline below a threshold, rather than by imposing interruptions of fixed duration.

Antiretroviral Therapy, Highly Active↗

Growth of human immunodeficiency virus-uninfected children exposed to perinatal zidovudine for the prevention of mother-to-child human immunodeficiency virus transmission.

BACKGROUND: Perinatal human immunodeficiency virus (HIV) prevention programs have been implemented in several countries, and many children have been or will be exposed to antiretrovirals in utero and during their first weeks of life. Although reducing substantially the number of infected children, the potential adverse consequences of these treatments on the health of HIV-uninfected children need to be assessed. OBJECTIVE: To investigate the impact of in utero and postnatal zidovudine exposure on the growth of HIV-uninfected children born to HIV-infected women. METHODS: We used data prospectively collected in 1408 live born children participating in a clinical trial comparing zidovudine regimens of different durations to prevent perinatal transmission in Thailand (PHPT-1). We used a linear mixed model to analyze the anthropometric measurements (weight for age, height for age and weight for height Z-scores) until 18 months of age according to zidovudine treatment duration (mothers, <7.5 weeks versus more; infants, 3 days versus >4 weeks). RESULTS: Children exposed in utero for >7.5 weeks had a slightly lower birth weight (Z-score difference, 0.08; P = 0.003). However, zidovudine exposure had no effect on the evolution of Z-scores from 6 weeks to 18 months of age. CONCLUSIONS: Although a longer in utero zidovudine exposure may have had a negative impact on birth weight, the magnitude of this effect was small and faded over time. Neither the total nor the postnatal duration of exposure was associated with changes in infant Z-scores from 6 weeks to 18 months of age.

Anti-HIV Agents↗

Drug interactions between lamotrigine and psychoactive drugs: evidence from a therapeutic drug monitoring service.

We present a systematic study on the interaction potential of lamotrigine, with focus on psychoactive drugs. A review of routine serum concentration measurements of lamotrigine performed in our laboratory yielded a total of 1733 serum samples from 829 patients (530 women, 299 men) suitable for statistical analysis. Main results for the whole study population were (median; interquartile range in parentheses): dose, 200 (100-300) mg; serum concentration, 2.97 (1.82-4.74) microg/mL; Lamotrigine serum concentration-to-dose ratio (LTG-CDR), 14.8 (9.9-24.6) (ng/mL)/(mg/d). A linear mixed model, allowing multiple observations from the same patient, was used to identify and quantitate the effect of factors influencing the LTG-CDR. In addition to age and gender, a total of 35 different comedications (25 drugs used in psychiatry as well as 10 other drugs) were evaluated. With women younger than 70 years as the reference group, factors found to lower the LTG-CDR significantly were: male gender and comedication with carbamazepine, ethinylestradiol, fluoxetine, lithium, phenytoin, phenobarbital, or topiramate. Factors associated with a significantly higher LTG-CDR were: age > or =70 years, and cotreatment with valproate. No antidepressants other than fluoxetine and none of the antipsychotic drugs included were associated with an altered LTG-CDR. Concerning pharmacokinetic drug interactions, we conclude that lamotrigine can be safely combined with most psychotropic drugs.

Adolescent↗

Homeless chronicity and health-related quality of life trajectories among adults with addictions.

BACKGROUND: New federal initiatives target funds toward chronically homeless as distinct from other homeless persons. Few data exist, however, to substantiate the implications of chronic homelessness for major health outcomes. OBJECTIVES: Using data from a 2-year cohort of addicted persons, we tested whether changes in mental and physical health-related quality of life (HRQOL) differed according to homeless chronicity. METHODS: Using self-reported homelessness, we classified subjects as chronically homeless (CH; n = 60), transitionally homeless (TRANS; n = 108), or as housed comparison subjects (HSD; n = 106). The Short Form-36 Health Survey, administered at baseline and 2 follow-ups over a period of 2 years, provided a Mental Component Summary (MCS) and a Physical Component Summary (PCS) for HRQOL. Mixed model linear regression was used to test the association between housing status, MCS, and PCS. Additional models assessed whether medical, psychiatric, addiction, and social support measures could account for HRQOL differences. RESULTS: All subjects had low MCS scores at study entry (mean, 31.2; SD, 12.6). However, there was a significant housing status-by-time interaction (P = 0.01). At final follow-up, CH and TRANS subjects had lower adjusted MCS scores than HSD subjects (33.4, 38.8, and 43.7 for the 3 groups, respectively; all P < or = 0.01). By contrast, housing status and PCS were not significantly associated (P = 0.19). Medical, psychiatric, addiction, and social support variables had significant associations with MCS, and their inclusion in the regression reduced the apparent effect of housing status on MCS. CONCLUSIONS: Chronic homelessness was associated with especially poor mental but not physical HRQOL over time. These findings reinforce a new typology of homelessness.

Adult↗