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Long-term effects of aerosolised rhDNase on pulmonary disease progression in patients with cystic fibrosis.

BACKGROUND: After multiple studies, including clinical trials, suggested some mild clinical benefits from the use of rhDNase by patients with cystic fibrosis, a widespread acceptance of the drug has followed. However, long-term effects, specifically on lung disease progression, have not been demonstrated. Experience with the use of this drug in a single cystic fibrosis centre is presented and compared with the trends seen in the patient population of the centre before the introduction of the drug. METHODS: Patients with cystic fibrosis routinely followed at the University of Minnesota Cystic Fibrosis Center and prescribed rhDNase for at least two years were included in this retrospective study. Data on spirometric parameters (FEV1 and FEV1/FVC), allometric index, and admissions to hospital were retrieved from the centre's database for the two years preceding the prescription of rhDNase and the two years that followed. Trends in pulmonary function and allometric index were analysed by mixed linear modelling, and hospital admission rates for both periods were calculated and compared. RESULTS: One hundred and ninety patients met the inclusion criteria for the study. In the two years preceding the prescription of rhDNase the trends noted were those of a mild decline in FEV1, a stable FEV1/FVC, and a mild improvement in allometric index. In the two years that followed the prescription of rhDNase a mild decline in all these parameters occurred which was a significant change from the previous period (all p < 0.009). There was no difference between females and males in the trends experienced after the start of rhDNase. By logistic regression analysis only the presence of malnutrition at the time of prescription was associated with a positive trend after the introduction of rhDNase. No significant change in the hospital admission rates occurred, with rates of 0.52 (0.16) and 0.56 (0.21) admissions/patient/year for the periods before and after the prescription of rhDNase, respectively. CONCLUSIONS: The introduction of rhDNase to the regimen of patients with cystic fibrosis cared for at this centre has not been followed by a positive trend in lung function and nutritional parameters. There are some differences between this patient population and those who participated in previous studies which may help to explain the contrasting findings of this study. However, it is also possible that factors other than mucus clearance need to be improved to achieve a favourable response in disease progression. Patients on this treatment should be followed closely and the benefit judged on an individual basis. More studies are needed to define better the specific indications and use of this form of treatment.

Adolescent↗

Prevalence and associations between bacterial isolates from dry mammary glands of dairy cows.

To assess the prevalence and patterns of bacterial isolates, cultures were made from the dry mammary glands of dairy cows in six commercial dairy herds in the UK. Milk samples were taken from all four quarters of 480 cows at drying off and at weekly intervals from 14 days before to seven days after calving. A major mastitis pathogen was isolated from at least one quarter of 220 (45.8 per cent) of the cows and from more than one quarter of 90 (18.8 per cent) of them. During the late dry to calving period, of the 957 quarters with three culture results, a major mastitis pathogen was cultured from 236 (24.7 per cent) quarters of 186 (38.8 [corrected] per cent) cows. The most commonly isolated major pathogen was Escherichia coli, followed by Streptococcus uberis and coagulase-positive staphylococci. There were significant differences between the patterns of isolates from different farms and in different calving months, suggesting that the rate of infection was partially dependent on external conditions. The isolation of E. coli, S. uberis or coagulase-positive staphylococci from a cow during the late dry/periparturient period was associated with an increased risk of that cow being culled in the next lactation. Bayesian general linear mixed models were used to assess the associations between the different bacterial species. The probability of isolating either E. coli or S. uberis was significantly greater when the other organism was cultured in a milk sample; this was also true of coagulase-positive staphylococci and S. uberis. When Corynebacterium species were isolated from a milk sample, the probability of isolating coagulase-positive staphylococci or S. uberis decreased significantly, and when coagulase-negative staphylococci were isolated the probability of isolating coagulase-positive staphylococci was reduced.

Animals↗

Experimental clonorchiasis in dogs: CT findings before and after treatment.

PURPOSE: To determine whether disease activity in clonorchiasis can be assessed with dynamic computed tomography (CT). MATERIALS AND METHODS: Ten dogs infected with metacercariae of Clonorchis sinensis underwent serial dynamic CT examinations. Five dogs were sacrificed 14 weeks after infection, and another five infected dogs were treated with praziquantel at the 14th week and continued to undergo CT examinations until death or sacrifice at the 25th (n = 1) or 40th week (n = 4). CT images were evaluated for dilatation of the bile ducts, contrast enhancement of bile duct walls and adjacent hepatic parenchyma, visualization of flukes within the bile ducts, and presence of calcifications. Changes in CT findings were analyzed statistically by using a mixed linear model and a generalized estimating equations model. RESULTS: Dilatation of the bile ducts, contrast enhancement of the ductal walls, transient hepatic attenuation differences, and flukes per se were observed at CT from the 2nd through the 5th week, were most apparent between the 5th and 13th weeks, and disappeared or decreased markedly in degree after treatment in all dogs (P <.05). Nodular calcifications were observed at CT after treatment in two dogs. Histopathologic examination revealed proliferation and enlargement of arteries in the periductal area and the portal tracts and congestion of hepatic sinusoids during the acute phase. Treatment was associated with periductal hyalinization, degeneration of the periductal arteries, and calcification of the ductal epithelium. CONCLUSION: Disease activity in experimental canine clonorchiasis can be assessed with dynamic CT.

Animals↗

Importance of comparison of current and prior mammograms in breast cancer screening.

PURPOSE: To retrospectively determine the influence of comparing current mammograms with prior mammograms on breast cancer detection in screening and to investigate a protocol in which prior mammograms are viewed only when necessary. MATERIALS AND METHODS: Institutional review board approval was not required. Participants gave written informed consent. Twelve experienced screening radiologists read 160 soft-copy screening mammograms twice, once with and once without prior mammograms. Eighty mammograms were obtained in women in whom breast cancer was diagnosed later; the other 80 mammograms had been reported as normal or benign. All cancers were visible in retrospect. Readers located potential abnormalities, estimated likelihood of malignancy for each finding, and indicated whether prior mammograms were considered necessary. The effect of prior mammograms on detection was determined by computing the mean lesion localized fraction in a range of low fractions of nonlesion locations corresponding to operating points in screening. Scores for both reading sessions were combined to assess the effect of making prior mammograms available only when requested. Data were analyzed by comparing the number of localized lesions between the two reading conditions with a paired two-tailed Student t test and applying a linear mixed model to test differences in average mean lesion localized fraction between reading conditions. P values less than .05 indicated statistical significance. RESULTS: Without prior mammograms, significantly more annotations were made. When only positive cases were considered, no difference was observed. Reading performance was significantly better when prior screening mammograms were available. At fixed lesion localized fraction, nonlesion localized fraction was reduced by 44% (P<.001) on average when prior mammograms were read. Performance was also increased for combined reading mode (ie, when prior mammograms were available on request only). However, this increase was smaller than that when prior mammograms were always available. Prior mammograms were requested in 24%-33% of all cases and were requested more often in positive cases. CONCLUSION: Comparison with prior mammograms significantly improves overall performance and can reduce referrals due to nonlesion locations. Limiting the availability of prior mammograms to cases selected by the reader reduces the beneficial effect of prior mammograms.

Aged↗

Normal fetal pelvis: important factors for morphometric characterization with US.

PURPOSE: To prospectively evaluate iliac angle and iliac length in a large number of normal fetuses and to identify factors that may influence these measurements. MATERIALS AND METHODS: At antenatal ultrasonography (US) in 356 fetuses, the iliac angle and iliac length were measured at two axial levels (superior and inferior). In mixed linear models, the statistical significance and magnitude of effect on the measurement of iliac angle and iliac length were estimated for gestational age, fetal sex, maternal diabetes status, axial level, and spine position relative to the transducer. RESULTS: Statistically significant effects were found for gestational age, axial level, and spine orientation but not for fetal sex or maternal diabetes status. The iliac angle was found to decrease by 15.7 degrees from the superior to inferior portion of the pelvis, decrease by approximately 0.37 degrees /wk, and decrease by as much as 15.6 degrees when the spine is directed to the side. Iliac length was found to increase by 0.8 mm/wk from 13 weeks to term, decrease by 1.2 mm from the superior to the inferior portion of the pelvis, and increase by as much as 1.29 mm when the spine is not directly subjacent to the transducer. CONCLUSION: The axial level of measurement, gestational age, and spine orientation must be accounted for if these morphometric indexes are used to discriminate fetuses with and those without Down syndrome.

Amniocentesis↗

Scale-space analysis of time series in circulatory research.

Statistical analysis of time series is still inadequate within circulation research. With the advent of increasing computational power and real-time recordings from hemodynamic studies, one is increasingly dealing with vast amounts of data in time series. This paper aims to illustrate how statistical analysis using the significant nonstationarities (SiNoS) method may complement traditional repeated-measures ANOVA and linear mixed models. We applied these methods on a dataset of local hepatic and systemic circulatory changes induced by aortoportal shunting and graded liver resection. We found SiNoS analysis more comprehensive when compared with traditional statistical analysis in the following four ways: 1) the method allows better signal-to-noise detection; 2) including all data points from real time recordings in a statistical analysis permits better detection of significant features in the data; 3) analysis with multiple scales of resolution facilitates a more differentiated observation of the material; and 4) the method affords excellent visual presentation by combining group differences, time trends, and multiscale statistical analysis allowing the observer to quickly view and evaluate the material. It is our opinion that SiNoS analysis of time series is a very powerful statistical tool that may be used to complement conventional statistical methods.

Analysis of Variance↗

Constitutive pro- and anti-inflammatory cytokine and growth factor response to exercise in leukocytes.

Leukocytosis following exercise is a well-described phenomenon of stress/inflammatory activation in healthy humans. We hypothesized that, despite this increase in circulating inflammatory cells, exercise would paradoxically induce expression of both pro- and anti-inflammatory cytokines and growth factors within these cells. To test this hypothesis, 11 healthy adult men, 18-30 yr old, performed a 30-min bout of heavy cycling exercise; blood sampling was at baseline, end-exercise, and 60 min into recovery. The percentage of leukocytes positive for intracellular cytokines and growth factors and mean fluorescence intensity was obtained by flow cytometry. Proinflammatory cytokines (IL-1alpha, IL-2, IFN-gamma, and TNF-alpha), a pleiotropic cytokine (IL-6), and anti-inflammatory cytokines and growth factors [IL-4, IL-10, growth hormone (GH), and IGF-I] were examined. Median fluorescence intensity was not affected by exercise; however, we found a number of significant changes (P < 0.05 by mixed linear model and modified t-test) in the numbers of circulating cells positive for particular mediators. The pattern of expression reflected both pro- and anti-inflammatory functions. In T-helper lymphocytes, TNF-alpha, but also IL-6, and IL-4 were significantly increased. In monocytes, both IFN-gamma and IL-4 increased. B-lymphocytes positive for GH and IGF-I increased significantly. GH-positive granulocytes also significantly increased. Collectively, these observations indicate that exercise primes an array of pro- and anti-inflammatory and growth factor expression within circulating leukocytes, perhaps preparing the organism to effectively respond to a variety of stressors imposed by exercise.

Adolescent↗

Common leptin receptor polymorphisms do not modify the effect of alcohol ingestion on serum leptin levels in a controlled feeding and alcohol ingestion study.

We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys109Arg), Q223R (Gln223Arg), S343S [Ser(T)343Ser(C)], and K656N (Lys656Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P > or = 0.26).

Adult↗

A retrospective evaluation of 1,25-dihydroxyvitamin D(3) and its potential effects on renal allograft function.

BACKGROUND/AIMS: 1,25-Dihydroxyvitamin D(3) (1,25-(OH)(2)D(3)) plays an important role in regulating immunologic responsiveness in addition to its effects on bone metabolism. This is potentially beneficial in the transplant setting. Animal studies have demonstrated the utility of 1,25-(OH)(2)D(3) in prolonging allograft survival. Therefore, we evaluated the effects of 1,25-(OH)(2)D(3) (oral calcitriol) in human renal transplant recipients. METHODS: A case-control study was undertaken assessing the effects of calcitriol on transplant function. The effect of calcitriol on renal function was analyzed using general linear mixed modeling of the change in slope of serum creatinine (Scr) prior to and following the start of calcitriol therapy. RESULTS: There was a significant increase in baseline Scr (p < 0.001) prior to starting calcitriol. Following initiation of calcitriol, there was a deceleration in the rate of loss of graft function (p = 0.031 at day 300 of therapy). Graft survival was also prolonged in calcitriol-treated patients compared to a control population with evidence of chronic allograft nephropathy but no calcitriol therapy (p < 0.03). Overall, there were no adverse or harmful effects related to calcitriol therapy. 1,25-(OH)(2)D(3) therapy was associated with (1) a deceleration in the rate of loss of renal function in transplant recipients with more than one year of allograft function, and (2) no significant change in allograft function early after transplantation. CONCLUSION: These data suggest that short- and long-term prospective trials evaluating 1,25-(OH)(2)D(3) or 1,25-(OH)(2)D(3) analogs in human kidney transplantation are warranted. Such trials may help us elucidate mechanism and duration of action, as well as safety issues related to these novel immunomodulatory agents.

Adult↗

Detoxifying capacity and kinetics of prometheus--a new extracorporeal system for the treatment of liver failure.

BACKGROUND/AIMS: Extracorporeal liver support therapies have been used for several decades as a bridging therapy prior to liver transplantation or as an addendum to standard medical therapy. The Prometheus system represents a cell-free, extracorporeal, liver assist method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the removal capacity and selectivity of the different inbuilt dialyzers and adsorption columns during a single 6-hour treatment. METHODS: Nine patients with acute on chronic liver failure were included (6 females, age 49+/- 4 years). Levels of endogenous toxins (urea nitrogen [UN, mg/dl], creatinine [Cr, mg/dl], total bilirubin [tB, mg/dl], and bile acids [BA, mumol/l]) and albumin [Alb, g/l] were monitored in blood sampled at different sites (arterial line, venous line and between the absorbers and the high-flux dialyzer) and at various time points (time 0, 30, 60, 120, 240, and 360 min). RESULTS: A significant decrease of the serum level of all toxins was observed (UN 108.7+/- 23.2 vs. 38.1+/- 14.9, Cr 2.4+/- 0.7 vs. 1.2+/- 0.3, tB 31.1+/- 4.1 vs. 17.0+/- 1.6, BA 155.7+/- 32.5 vs. 66.0+/- 15.4; mean+/- SEM, time 0 vs. time 360, signed rank rest, all p< 0.005). The reduction rate of UN, Cr, tB and BA amounted to 68.1+/- 5.1, 45.9+/- 6.2, 41.2+/- 5.1, and 58.2+/- 5.0%, respectively. Blood clearances [Cl, ml/min] of all, but especially of the protein-bound toxins declined over time (Cl UN 171.5+/- 4.3 vs. 142.9+/- 16.8; Cl Cr 135.7+/- 10.0 vs. 111.8+/- 9.1; Cl tB 29.3+/- 5.1 vs. 13.7+/- 3.7; Cl BA 84.9+/- 4.8 vs. 45.1+/- 13.3; time 30 vs. time 360; linear mixed models, all p< 0.005). Serum albumin levels decreased by 2.9+/- 0.9 g/l (signed rank test, p=0.055). Not unexpectedly, tB was almost uniquely cleared by the adsorbers (UN 0.2+/-1.1, Cr 6.9+/- 5.7, tB 92.3+/- 4.2, BA 62.9+/- 3.9% of total Cl). CONCLUSION: Both albumin-bound and water-soluble toxins are adequately removed by the Prometheus system. Our data suggest that the rate and efficacy of removal of albumin-bound toxins is related to both the strength of the albumin binding and the saturation of the adsorption columns. Limited losses of albumin occur during treatment with the Prometheus system.

Bile Acids and Salts↗

Micellar phytosterols effectively reduce cholesterol absorption at low doses.

BACKGROUND: The objective of this study was to evaluate the effects of micellar phytosterols on cholesterol absorption in humans. METHODS: 24 healthy adults (mean age 37 years, 16 women and 8 men) underwent four cholesterol-absorption tests to compare the effects of micellar phytosterols supplement containing 500, 300, 200 mg phytosterols and placebo on cholesterol absorption in a cross-over design. Individual absorption tests were separated by 2 weeks. Using the single oral isotope method, inhibition of cholesterol absorption was determined by gas-chromatography mass spectrometry measurement of the differences in plasma hexadeuterated cholesterol enrichment 4 days after test meals with or without phytosterols. Each test meal provided 500 kcal and 89 mg cholesterol including 40 mg tracer cholesterol. We used a general linear mixed model with SAS to test the significance of treatment effect. RESULTS: Micellar phytosterols had a significant overall effect on cholesterol absorption (p = 0.0002), reduced cholesterol absorption by 23.3% at a dose of 300 mg phytosterols (p = 0.0004) and by 32.0% at a dose of 500 mg phytosterols (p = 0.0001) compared with the placebo. The effect of 200 mg treatment did not reach statistical significance but there was a tendency (p = 0.052). CONCLUSION: Water-dispersible, micellar phytosterols reduced cholesterol absorption effectively at very low doses.

Adult↗

Effects of rapid versus slow infusion of sodium bicarbonate on cerebral hemodynamics and oxygenation in preterm infants.

BACKGROUND: Sodium bicarbonate (NaHCO3) is often used for correction of metabolic acidosis in preterm infants. The effects of NaHCO3 administration on cerebral hemodynamics and oxygenation are not well known. Furthermore, there is no consensus on infusion rate of NaHCO3. OBJECTIVES: To evaluate the effects of rapid versus slow infusion of NaHCO3 on cerebral hemodynamics and oxygenation in preterm infants. METHODS: Twenty-nine preterm infants with metabolic acidosis were randomized into two groups (values are mean +/-SD): In group A (GA 30.5 +/- 1.7 weeks, b.w. 1,254 +/- 425 g) NaHCO3 4.2% was injected as a bolus. In group B (GA 30.3 +/- 1.8 weeks, b.w. 1,179 +/- 318 g) NaHCO3 4.2% was administered over a 30-min period. Concentration changes of oxyhemoglobin (cO2Hb) and deoxyhemoglobin (cHHb) were assessed using near infrared spectrophotometry. Changes in HbD (= cO2Hb - cHHb) represent changes in cerebral blood oxygenation and changes in ctHb (= cO2Hb + cHHb) reflect changes in cerebral blood volume. Cerebral blood flow velocity was intermittently measured using Doppler ultrasound. Longitudinal data analysis was performed using linear mixed models (SAS procedure MIXED), to account for the fact that the repeated observations in each individual were correlated. RESULTS: Administration of NaHCO3 resulted in an increase of cerebral blood volume which was more evident if NaHCO3 was injected rapidly than when infused slowly. HbD and cerebral blood flow velocity did not show significant changes in either group. CONCLUSION: To minimize fluctuations in cerebral hemodynamics, slow infusion of sodium bicarbonate is preferable to rapid injection.

Acidosis↗

Effects of midazolam and morphine on cerebral oxygenation and hemodynamics in ventilated premature infants.

BACKGROUND: Midazolam sedation and morphine analgesia are commonly used in ventilated premature infants. OBJECTIVES: To evaluate the effects of midazolam versus morphine infusion on cerebral oxygenation and hemodynamics in ventilated premature infants. METHODS: 11 patients (GA 26.6-33.0 weeks, BW 780-2,335 g) were sedated with midazolam (loading dose 0.2 mg/kg, maintenance 0.2 mg/kg/h) and 10 patients (GA 26.4-33.3 weeks, BW 842-1,955 g) were sedated with morphine (loading dose 0.05 mg/kg, maintenance 0.01 mg/kg/h). Changes in oxyhemoglobin (Delta cO2Hb) and deoxyhemoglobin (Delta cHHb) were assessed using near infrared spectrophotometry. Changes in cHbD (= Delta cO(2)Hb - Delta cHHb) reflect changes in cerebral blood oxygenation and changes in concentration of total hemoglobin (Delta ctHb = Delta cO2Hb + Delta cHHb) represent changes in cerebral blood volume (DeltaCBV). Changes in cerebral blood flow velocity (DeltaCBFV) were intermittently measured using Doppler ultrasound. Heart rate (HR), mean arterial blood pressure (MABP), arterial oxygen saturation (saO2) and transcutaneous measured pO2 (tcpO2) and pCO2 (tcpCO2) were continuously registered. Statistical analyses were carried out using linear mixed models to account for the longitudinal character study design. RESULTS: Within 15 min after the loading dose of midazolam, a decrease in saO2, tcpO2 and cHbD was observed in 5/11 infants. In addition, a fall in MABP and CBFV was observed 15 min after midazolam administration. Immediately after morphine infusion a decrease in saO2, tcpO2 and cHbD was observed in 6/10 infants. Furthermore, morphine infusion resulted in a persistent increase in CBV. CONCLUSIONS: Administration of midazolam and morphine in ventilated premature infants causes significant changes in cerebral oxygenation and hemodynamics, which might be harmful.

Blood Flow Velocity↗

Genetic and environmental contributions to platelet aggregation: the Framingham heart study.

BACKGROUND: Platelet aggregation plays an important role in arterial thrombosis in coronary heart disease, stroke, and peripheral arterial disease. However, the contribution of genetic versus environmental influences on interindividual variation in platelet aggregability is poorly characterized. METHODS AND RESULTS: We studied the heritability of platelet aggregation responses in 2413 participants in the Framingham Heart Study. The threshold concentrations of epinephrine and ADP required to produce biphasic platelet aggregation and collagen lag time were determined. Mixed-model linear regression was used to calculate correlation coefficients within sibships and within spouse pairs. Variance and covariance component methods were used to estimate the proportion of platelet aggregation attributable to measured covariates versus additive genetic effects. After accounting for environmental covariates, the adjusted sibling correlations for epinephrine, ADP, and collagen lag time were 0.24, 0.22, and 0.31, respectively (P=0.0001 for each). In contrast, adjusted correlations for spouse-pairs were -0.01, 0.05, and -0.02, respectively (all P>0.30). The estimated heritabilities were 0.48, 0.44, and 0.62, respectively. Measured covariates accounted for only 4% to 7% of the overall variance in platelet aggregation, and heritable factors accounted for 20% to 30%. The platelet glycoprotein IIIa Pl(A2) polymorphism and the fibrinogen Hind III beta-148 polymorphism contributed <1% to the overall variance. CONCLUSIONS: In our large, population-based sample, heritable factors play a major role in determining platelet aggregation, and measured covariates play a lesser role. Future studies are warranted to identify the key genetic variants that regulate platelet function and to lay the groundwork for rational pharmacogenetic approaches.

Adenosine Diphosphate↗

Treatment variation in older black and white patients undergoing aortic valve replacement.

BACKGROUND: Most prior studies of racial differences in the delivery of cardiac care have focused on potential differences in treatment by individual physicians and hospitals. However, differential use of hospitals with variable practice patterns might also contribute to variations in care. METHODS AND RESULTS: We compared the use of bioprosthetic valves (BPVs) in 78,154 black and white Medicare beneficiaries > or =65 years of age undergoing aortic valve replacement in 904 US hospitals during 1999 through 2001. Generalized linear mixed models were used to account first for differences in patient characteristics and then for differences in hospitals used by black and white patients. BPV use was lower in black patients relative to white patients after adjustment for patient characteristics (relative risk, 0.93; 95% CI, 0.91 to 0.95; P<0.001). However, black patients were more likely to undergo surgery in hospitals in the lowest quintile of BPV use overall (29% versus 20% of white patients; P<0.001). After hospital-level variability in BPV use was accounted for, the use of BPVs was actually somewhat higher in black patients (relative risk, 1.06; 95% CI, 1.04 to 1.09; P<0.001). Model discrimination as measured by the c statistic was markedly higher after the addition of hospital effects (0.80 versus 0.59 for patient characteristics alone; P<0.001). CONCLUSIONS: Accounting for differences in hospitals preferentially used by black and white patients had a major impact on estimating racial differences in the use of BPVs in patients undergoing aortic valve replacement. Hospital-level effects explained a larger proportion of the variation in BPV use than race and other patient characteristics alone.

Adult↗

Analysis of the patient-therapist relationship in dynamic psychotherapy: an experimental study of transference interpretations.

OBJECTIVE: The purpose of this study was to measure the effects of transference interpretations (the assumed core active ingredient) in dynamic psychotherapy, using an experimental design. METHOD: One hundred patients were randomly assigned to two groups. One group received dynamic psychotherapy over 1 year, with a moderate level of transference interpretations, while the other group received dynamic psychotherapy with no transference interpretations. The most common axis I disorders were depression and anxiety disorders. Forty-six patients fulfilled the general criteria for personality disorder. Seven experienced psychotherapists treated patients in both groups. Five full sessions from each treatment were rated by two evaluators with process measures in order to document treatment integrity. Outcome variables were the Psychodynamic Functioning Scales, Inventory of Interpersonal Problems Scale-Circumplex version, Global Assessment of Functioning Scale, and Symptom Checklist-90-R. Quality of Object Relations Scale (lifelong pattern) and personality disorders were preselected as possible moderators of treatment effects. Change was assessed using linear-mixed models. Clinically significant change was also calculated. RESULTS: The authors could not demonstrate differential treatment effects between the groups. However, the moderator analyses showed that transference interpretations were more helpful for patients with a lifelong history of less mature object relations. Small negative effects were observed for patients with mature object relations. CONCLUSIONS: The authors could not show differences in average effectiveness between treatments. However, the moderator analyses indicated that treatment worked through different active ingredients for different patients. Contrary to common expectation, patients with poor object relations profited more from therapy with transference interpretations than from therapy with no transference interpretations.

Adult↗

A double-blind, placebo-controlled study of memantine in the treatment of major depression.

OBJECTIVE: This study was designed to assess possible antidepressant effects of memantine, a selective N-methyl-D-aspartate (NMDA) receptor antagonist in humans. METHOD: In a double-blind, placebo-controlled study, 32 subjects with major depression were randomly assigned to receive memantine (5-20 mg/day) (N=16) or placebo (N=16) for 8 weeks. Primary efficacy was assessed by performance on the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: The linear mixed models for total MADRS scores showed no treatment effect. CONCLUSIONS: In an 8-week trial, the low-to-moderate-affinity NMDA antagonist memantine in doses of 5-20 mg/day was not effective in the treatment of major depressive disorder.

Major Depressive Disorder↗

Household income histories and child mental health trajectories.

Although it is widely accepted that low household income is associated with worse child mental health, less is known about whether income histories, often differentiated into stable and dynamic components, also matter. Using longitudinal data from the Child Supplement of the National Longitudinal Study of Youth, comprising the repeated measures of children ages 4 to 14 from 1986 to 1998 inclusive, I estimate generalized linear mixed models to evaluate the influence of household income histories on child depression and antisocial behavior over time. Results indicate that, at initial interview, low household income is associated with higher levels of depression and antisocial behavior; subsequent improvements in household income reduce child mental health problems. Further, the effect of initial household income on the rate of change in child depression attenuates as children grow older, whereas for antisocial behavior the effect of initial household income becomes stronger over time. These findings highlight the importance of understanding the ways in which children are influenced by their families' income histories.

Adolescent↗