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PubMed1996

Induction of apoptosis by La Crosse virus infection and role of neuronal differentiation and human bcl-2 expression in its prevention.

La Crosse virus causes a highly cytopathic infection in cultured cells and in the murine central nervous system (CNS), with widespread neuronal destruction. In some viral infections of the CNS, apoptosis, or programmed cell death, has been proposed as a mechanism for cytopathology (Y. Shen and T. E. Shenk, Curr. Opin. Genet. Dev. 5:105-111, 1995). To determine whether apoptosis plays a role in La Crosse virus-induced cell death, we performed experiments with newborn mice and two neural tissue culture models. Newborn mice infected with La Crosse virus showed evidence of apoptosis with the terminal deoxynucleotidyl transferase-mediated nicked-end labeling (TUNEL) assay and, concomitantly, histopathological suggestion of neuronal dropout. Infection of tissue culture cells also resulted in DNA fragmentation, TUNEL reactivity, and morphological changes in the nuclei characteristic of apoptotic cells. As in one other system (S. Ubol, P. C. Tucker, D. E. Griffin, and J. M. Hardwick, Proc. Natl. Acad. Sci. USA 91:5202-5206, 1994), expression of the human proto-oncogene bcl-2 was able to protect one neuronal cell line, N18-RE-105, from undergoing apoptosis after La Crosse virus infection and prolonged the survival of infected cells. Nevertheless, expression of bcl-2 did not prevent eventual cytopathicity. However, a human neuronal cell line, NT2N, was resistant to both apoptosis and other types of cytopathicity after infection with La Crosse virus, reaffirming the complexity of cell death. Our results show that apoptosis is an important consequence of La Crosse virus infection in vivo and in vitro.

Animals↗
PubMedDate not supplied

Impact of study design and patient population on outcomes from cholinesterase inhibitor trials.

The authors conducted a comparative review of study designs and patient populations used in pivotal trials investigating various cholinesterase inhibitors (tacrine, donepezil, rivastigmine, galantamine, controlled-release physostigmine, and metrifionate) and their impact on outcomes reported. Study design parameters that were investigated included patient selection, definitions of adverse dropouts and serious adverse events, effective doses used, dosing flexibility (fixed versus flexible), forced titration, and titration rate. Population characteristics included medical comorbidity and disease severity. Data suggest that differences in study designs and patient populations affect outcomes. Therefore, caution should be taken before making decisions on relative efficacy, safety, and tolerability, because clinical studies are not always directly comparable.

Aged↗
PubMed1997

The Amsterdam Growth and Health Longitudinal Study. The past (1976-1996) and future (1997-?).

This article presents an overview of the Amsterdam Growth and Health Longitudinal Study (AGAHLS). This study was started in the 1970s, following a whole sample of 500 healthy 13-year-old boys and girls from two secondary schools. During the school period (12-17 years) annual measurements were performed with respect to anthropometrics, physiological and psychological parameters, lifestyle characteristics (activity, diet, smoking) and health parameters. A multiple longitudinal design was applied with overlapping birth cohorts and a cross-sectional measured control group to monitor for confounding factors such as time of measurement, cohort, dropout and testing effects. Emphasis is also placed on measures that enhance adherence of the subjects. The follow-up was extended with repeated measurements at age 21, 26 and 28. This enabled us to analyze the data with respect to tracking characteristics of biological and lifestyle variables over a period of 15 years between adolescence and adulthood and also to investigate quasi-causal relationships between the effects of a healthy lifestyle and indicators for cardiovascular diseases (CVD). Also new methods such as measurement of atherosclerosis and osteoporosis will be added and related to longitudinal measurements of the same subjects in the past. The main results that were obtained in the past are summarized and research questions for the near future are explained.

Adolescent↗
PubMed1993

Adolescent mothers and repeated childbearing: effects of a school-based intervention program.

This study examined the effectiveness of a public school program for pregnant teenagers in preventing rapid repeated childbearing. Students permitted to attend longer than seven weeks postpartum were much more likely to avoid having another child in the next five years than were students required to return to their regular schools. The results indicate the potential of school-based programs to improve life outcomes for adolescent mothers and their children.

Adolescent↗
PubMed1983

[3 osteosarcoma therapy dropouts. Clinical cases].

We report on 3 cases of male late-adolescent/young-adult osteogenic sarcoma patients who refused complete chemical therapy according to the treatment plan "COSS 80". They all originated from disturbed family situations. Characteristic was their early independence and autonomy, dominance tendency, low level of self control, and high level of sociability. Primary motivation for refusal was the experienced intolerability of the chemotherapeutical side-effects and extreme fear of medical procedures (e.g. injections).

Adolescent↗
PubMedDate not supplied

Dropout from brief psychotherapy in anorexia nervosa.

BACKGROUND: Dropout from psychotherapy is an important issue that has received little systematic attention. This study investigated the phenomenon of dropout from brief psychotherapy for anorexia nervosa (AN). METHODS: 99 outpatients suffering from AN of the restrictor type (n = 53) or binge/purging type (n = 46) were evaluated. Their clinical and personal characteristics were recorded, and body mass index was calculated for participants. They were administered the Eating Disorder Inventory-II (EDI-II), the State-Trait Anger Expression Inventory (STAXI) and the Temperament and Character Inventory (TCI). RESULTS: Significant differences in some baseline psychopathologic (EDI-II, STAXI) and personality (TCI) variables emerged from the comparison between dropouts and completers. Patients who dropped out of the treatment showed higher levels of anger temperament, anger expression-in and expression-out and lower scores for the dimensions of character (low self-directedness and low cooperativeness). No differences were found between the two groups regarding sociodemographic and clinical variables. CONCLUSIONS: Dropout from brief psychotherapy seems to be related to either psychopathologic or personality aspects, such as the tendency to repress anger, which is encountered also in psychosomatic disorders, and the presence of more compromised dimensions of character, typical of subjects with personality disorders. This study of dropout from brief psychotherapy in AN provided interesting results that will need further confirmation. Possible implications for treatment are addressed.

Adolescent↗
PubMed2006

Educational achievement and early school behavior as predictors of alcohol-use disorders: 35-year follow-up of the Woodlawn Study.

OBJECTIVE: Using prospectively gathered data across a 35-year follow-up interval, we assessed the association of educational achievement and school behaviors with risk for the development of an alcohol-use disorder in adulthood. METHOD: The baseline population consisted of 1242 first-grade students in 1966-1967 residing in the Woodlawn community of Chicago, Illinois. Follow-up interviews were completed for adolescents and their mothers (1975-1976), during young adulthood (1992-1993), and midlife (2002-2003). A total of 1052 individuals completed the young adult and/or midlife interviews and provided information to assess the presence of a lifetime alcohol-use disorder. Logistic regression with multiple imputation to account for missing information was used to assess the relationships between early-educational and school-behavior characteristics with onset of a DSM-III-R/DSM-IV alcohol-use disorder (defined using the Composite International Diagnostic Interview). RESULTS: Relatively few of the hypothesized educational predictors were associated with risk for alcohol-use disorders in adulthood. The measures found to be predictive of a subsequent alcohol-use disorder included the following: (1) math achievement among first-grade boys, (2) mothers' report of skipping school among adolescent males, (3) self-report of skipping school among adolescent girls, and (4) school dropout. Early shyness among first-grade boys was protective for later alcohol-use disorders. CONCLUSIONS: The current report supplies data on the association of educational characteristics and school behaviors with the development of an alcohol-use disorder in a population-based sample with an extended interval of follow-up. Gender-specific differences are discussed.

Achievement↗
PubMed2006

Duloxetine compared with fluoxetine and venlafaxine: use of meta-regression analysis for indirect comparisons.

BACKGROUND: Data comparing duloxetine with existing antidepressant treatments is limited. A comparison of duloxetine with fluoxetine has been performed but no comparison with venlafaxine, the other antidepressant in the same therapeutic class with a significant market share, has been undertaken. In the absence of relevant data to assess the place that duloxetine should occupy in the therapeutic arsenal, indirect comparisons are the most rigorous way to go. We conducted a systematic review of the efficacy of duloxetine, fluoxetine and venlafaxine versus placebo in the treatment of Major Depressive Disorder (MDD), and performed indirect comparisons through meta-regressions. METHODS: The bibliography of the Agency for Health Care Policy and Research and the CENTRAL, Medline, and Embase databases were interrogated using advanced search strategies based on a combination of text and index terms. The search focused on randomized placebo-controlled clinical trials involving adult patients treated for acute phase Major Depressive Disorder. All outcomes were derived to take account for varying placebo responses throughout studies. Primary outcome was treatment efficacy as measured by Hedge's g effect size. Secondary outcomes were response and dropout rates as measured by log odds ratios. Meta-regressions were run to indirectly compare the drugs. Sensitivity analysis, assessing the influence of individual studies over the results, and the influence of patients' characteristics were run. RESULTS: 22 studies involving fluoxetine, 9 involving duloxetine and 8 involving venlafaxine were selected. Using indirect comparison methodology, estimated effect sizes for efficacy compared with duloxetine were 0.11 [-0.14;0.36] for fluoxetine and 0.22 [0.06;0.38] for venlafaxine. Response log odds ratios were -0.21 [-0.44;0.03], 0.70 [0.26;1.14]. Dropout log odds ratios were -0.02 [-0.33;0.29], 0.21 [-0.13;0.55]. Sensitivity analyses showed that results were consistent. CONCLUSION: Fluoxetine was not statistically different in either tolerability or efficacy when compared with duloxetine. Venlafaxine was significantly superior to duloxetine in all analyses except dropout rate. In the absence of relevant data from head-to-head comparison trials, results suggest that venlafaxine is superior compared with duloxetine and that duloxetine does not differentiate from fluoxetine.

Antidepressive Agents↗
PubMed2004

[A pitfall in analyses of relevant factors concerning phenomena in the process of initiating dialysis: alterations in the characteristics of subjects diminish the significance of age].

In our previous studies, relevant factors concerning the main phenomena related to the process of initiating dialysis were examined in elderly patients with chronic renal failure. Examined phenomena were as follows: (1) the acceptance of dialysis; (2) the urgency of initiating dialysis; (3) short-term outcome; (4) returning home. Multivariate logistic regression analysis was used to determine relevant factors. Although we speculated that age should be a relevant factor for each phenomenon, the phenomenon on which age had some impact was only the first. We suspected the existence of a pitfall, through which the relation of age was lost in the second, the third, or the fourth phenomenon. The fact that every phenomenon had its own relevant factors was thought to be an important clue to the discovery of pitfalls. Relevant factors were derived from both the number of dropout-patients and their demographic and clinical status. From the viewpoint of nondropout-patients, the progression of the process of initiating dialysis might alter the characteristics of subjects for successive phenomena In this study, we set out to investigate whether alterations in the characteristics of subjects were pitfalls. Alterations were regarded as a fall of the mean age, an increment of the rate of the patients with ability to walk, and an increment of the rate of the patients with normal cognitive function. In addition, the old-old patients tended to have limited numbers of those who had the ability to walk and normal cognitive function. In other words, aging changes in ambulatory and cognitive function were not brought to subjects. These alterations may cause the loss of the relation of age to each phenomenon. Thus, we presumed these alterations to be pitfalls. We must clarify whether aging changes are brought to subjects beforehand in analyses that include the old-old patients as subjects.

Age Factors↗
PubMed2003

Resident physicians who continue Balint training: a longitudinal study 1982-1999.

BACKGROUND AND OBJECTIVES: Balint seminars began in London in 1950 on a voluntary basis for general practitioners wishing to explore psychological problems in their practice. By 1964, there was a 36% early dropout rate among the 223 physicians who participated. This study sought to determine if those who leave Balint training during their residency, versus those who continue, have different psychological characteristics. METHODS: A retrospective analysis of 206 Medical University of South Carolina family practice residents from 1982 to 1999 was completed. All residents participated in 6 months of required Balint training and then could leave the Balint group or continue for the remaining 2 years. We examined gender and personality attributes, comparing residents who completed 2 years of weekly Balint training and residents who left after 6 months. Personality attributes were measured with the Myers-Briggs Inventory, the Work Environmental Preference Schedule, the Internal-External Locus of Control, the Fundamental Interpersonal Relationship Orientation Behavior test, and the Personal Orientation Inventory. RESULTS: A total of 132 residents completed 2 years of weekly Balint training, and 74 discontinued training after 6 months. Two-year attendees were significantly more intuitive on the Myers-Briggs Personality Inventory (MBTI). There were no significant differences on other MBTI items, nor were there significant differences in gender or in scores on the other psychological tests. CONCLUSIONS: Based on the rate of discontinuation of Balint training in our sample, Balint work does not appear to be suited to all physicians. With the exception of one MBTI characteristic, no significant differences could be demonstrated between those who did and did not continue participating. Further study is necessary to define other attributes characterizing Balint group attendees and nonattendees.

Family Practice↗
PubMed2001

The placebo response in social phobia.

The placebo response forms a growing problem in randomized, placebo-controlled clinical trials in psychiatry. Research into the placebo response is on the increase, but remains very limited in relation to social phobia. Together with the dropout rate, the placebo effect is an important factor limiting the discriminative properties of any study. In this study, we reviewed 15 placebo-controlled studies in social phobia, focussing on patients and study characteristics. In social phobia, the placebo effect has turned out to be moderately large and has shown no increase over the past decade. Placebo response was highest in large, multicentred trials and was independent of study duration. No validation for a placebo run-in was found. Taking into account both response to placebo and active drug, as well as dropout rate, the most discriminative results are probably to be expected in a sample of patients who are moderately to severely impaired. More research in the field of the placebo response is needed.

Double-Blind Method↗