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PubMed2002

The association of erythromycin and infantile hypertrophic pyloric stenosis: causal or coincidental?

The safety profile of erythromycin is notable for the frequent occurrence of intolerable gastrointestinal effects. One of the more serious of these is infantile hypertrophic pyloric stenosis (IHPS). A recent cluster of IHPS cases prompted an epidemiological investigation which identified oral erythromycin chemoprophylaxis of pertussis as the major risk factor. Evidence suggests an association between early postnatal erythromycin exposure and IHPS. There is no substantive evidence of a risk associated with prenatal exposure, with the single published case-control study to date producing negative findings. The epidemiological investigations of the association with early postnatal exposure have reported significantly elevated odds ratios but have a variety of methodological limitations that prevent definitive conclusions being made. Nevertheless, the concordance of findings across studies increases the strength of evidence favouring an association. The prominent gastrokinetic properties of erythromycin have been postulated as the mechanism behind this phenomenon. A comprehensive assessment of this potential adverse effect should consider its biological plausibility in light of known gastrointestinal physiology, its modulation by erythromycin, and the known pathophysiology of IHPS. Gastrointestinal motor activity in the fasted mammal consists of three phases, phase III being large amplitude contractions called migrating motor complexes (MMC) that can be initiated by motilin and erythromycin. The gastrokinetic effects of erythromycin are variable and complex and include effects on the timing, duration, amplitude and distribution of MMCs. It has been speculated that the motilinomimetic effects of erythromycin on antral smooth muscle function, such as the MMC, may mediate the effect via work hypertrophy. Although intuitively plausible and consistent with hypertrophic obstructive changes similar to IHPS observed in hyperplastic rat ileum after artificially induced mechanical obstruction, there is no direct evidence of this phenomenon. Further complicating the association is the limitations of our knowledge about the pathophysiology of IHPS, including numerous genetic abnormalities, increased parietal cell mass, and gastric hyperacidity. The implications of the reported findings with erythromycin on the benefit-risk profiles of newer macrolides and azalides must be considered. The available data on the comparative gastrokinetic properties of macrolides are significant for the potent gastrokinetic properties and its acid degradation products, the marked variation in gastrokinetic properties associated with macrolide ring size, and the requirement for specific glycosidic linkages at the C-3 and C-5 carbons of the macrolide ring. The variation in gastrokinetic properties associated with variations in molecular structure suggests that if the association between erythromycin and IHPS is causal it may not be a class effect.

Adverse Drug Reaction Reporting Systems↗

PubMed2004

MMR vaccination and autism : what is the evidence for a causal association?

It has been suggested that vaccination with the measles-mumps-rubella (MMR) vaccine causes autism. The wide-scale use of the MMR vaccine has been reported to coincide with the apparent increase in the incidence of autism. Case reports have described children who developed signs of both developmental regression and gastrointestinal symptoms shortly after MMR vaccination.A review of the literature revealed no convincing scientific evidence to support a causal relationship between the use of MMR vaccines and autism. No primate models exist to support the hypothesis. The biological plausibility remains questionable and there is a sound body of epidemiological evidence to refute the hypothesis. The hypothesis has been subjected to critical evaluation in many different ways, using techniques from molecular biology to population-based epidemiology, and with a vast number of independent researchers involved, none of which has been able to corroborate the hypothesis.

Animals↗

PubMed2006

Reye's syndrome: the case for a causal link with aspirin.

Reye's syndrome is a serious, acute encephalopathy that has been linked with aspirin (acetylsalicylic acid) use in children and teenagers <18 years of age. Although others may disagree, it is my belief that any objective analysis of published material in the last 20 years must conclude that there is a close link between the devastating encephalopathy Reye's syndrome and ingestion of aspirin during the febrile prodrome. The drug appears to act as a co-factor in susceptible individuals. Although some of the epidemiological data indicate an association between the two, the burden of evidence suggests actual causality and is both consistent and specific as well as strong and time related. Some of the evidence points to illness severity being dose related although it seems that in the presence of a viral infection, no dose of aspirin can be considered safe. No published work, using methodology that can be critically evaluated, has shown evidence to contradict these conclusions and they have been widely accepted. Since government health warnings were appended to aspirin-containing formulations, the decline in case numbers on both sides of the Atlantic has been nothing short of remarkable. Recent in vitro findings have pinpointed the site of action of the drug on the long chain hydroxyacyl-CoA dehydrogenase enzyme (a component of the mitochondrial trifunctional enzyme) and, even at therapeutic concentrations, oxidation is impaired in cultured fibroblasts from patients who have recovered from the disorder. This is quite unlike that seen in cells from normal controls. Even when major influenza outbreaks occur in the future, Reye's syndrome is preventable provided government health warnings are heeded and the cogent evidence set forth here is acted upon by the parents of feverish children and self-medicating teenagers.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2001

Quality-of-life assessment in comparative therapeutic trials and causal structure considerations in peripheral occlusive arterial disease.

When considering the use of quality of life as a primary end-point in phase III to IV comparative trials, the trial designer generally faces some unresolved questions. These include: How does one explain that some dimensions [quality-of-life (QOL) instruments usually have more than 1 dimension] are directly influenced by the studied treatments whereas others are not? How can one interpret conflicting results between conventional clinical measurements and QOL measurements, when the relationships between conventional clinical measurement and quality of life are not known? In this paper, we consider the use of Structural Equation Modelling (SEM) as a methodological alternative to answer these problems. As an example, we analyse the internal causal structure of the Claudication Scale (CLAU-S), a specific QOL 5-dimensional instrument for peripheral occlusive arterial disease. In applying SEM to different studies and different types of calculation, we suggest that CLAU-S is based on a stable, simple and comprehensive QOL model, is compatible with the general International Classification of Impairments, Disabilities and Handicaps (ICIDH) classification, is coherent and complementary with clinical data measurements and, using differences in a prospective study, considerably improves specificity. We suggest that SEM can help in QOL scale validation, in providing a unified scheme of the inter-relationships between internal dimensions and with external variables, in particular, clinical measurements.

Arterial Occlusive Diseases↗

PubMed2003

Is there a causal relationship between exposure to diesel exhaust and multiple myeloma?

This article presents a comprehensive critical review of the epidemiology of multiple myeloma in relation to occupational diesel exhaust exposure. The review includes cohort and proportional mortality studies of workers exposed to diesel exhaust, and population-based case-control studies of multiple myeloma. None of the cohort or proportional mortality studies reported a significant increase of multiple myeloma in relation to diesel exhaust, with the exception of a study of Danish truck drivers. Several limitations in this Danish study (such as inadequate cohort identification, small number of multiple myeloma deaths and inappropriate analytical method) made the result unreliable. Furthermore, the data in this study of Danish truck drivers were part of and, hence, superseded by a large study in Denmark, which did not find any increased risk of multiple myeloma. Similarly, none of the case-control studies reported a significant increase of multiple myeloma in relation to diesel exhaust, with the exception of the smallest case-control study based on multiple myeloma patients in central and southeast Sweden. The result of this small Swedish study was not reliable because of incomplete case ascertainment, inappropriate controls and confounding. Furthermore, the data in this small Swedish study were part of and, hence, superseded by a large national study of workers exposed to diesel exhaust in Sweden, which did not find any increased risk of multiple myeloma. Other than the study of Danish truck drivers and the small case-control study of multiple myeloma patients in central and southeast Sweden, all other epidemiological investigations consistently reported no increase of multiple myeloma in relation to occupational diesel exhaust exposure. Furthermore, none of the studies reported a positive exposure-response relationship between diesel exhaust and multiple myeloma. Several studies that analysed data by jobs or occupations according to level of exposure and by duration of exposure did not find any upward trend. In addition to the review, a formal causation analysis based on an application of the Hill criteria confirms that there is no causal relationship between diesel exhaust and multiple myeloma.

Denmark↗

PubMedDate not supplied

Causal attribution and life-threatening disease.

When individuals are confronted with a diagnosis of serious disease, they try to understand why it has happened to them. The degree to which any individual can control his or her susceptibility to disease is not clear, but different diseases carry with them varying degrees of implied personal responsibility. For example, certain diseases (heart attack, stroke, cancer) have associated risk factors. Presumably, avoiding these risk factors will have some effect on a person's chance of developing those diseases. The purpose of this secondary analysis was to describe patients' attributed causes for two groups of individuals recently diagnosed with either lung cancer or myocardial infarction. Content analysis was done on the responses to an open-ended question about the cause of their disease for 108 subjects at Interview 1 and for 100 subjects at Interview 2. The most frequent causal explanations given by post myocardial infarction subjects in this study were related to life style, which could be interpreted as self-blame or self responsibility for what had happened to them. In contrast, the subjects with lung cancer more consistently said that they did not know what caused their disease, or mentioned a combination of life style (smoking) and external factors (exposure to noxious fumes or asbestos).

Adult↗

PubMed2004

A general causal model to guide alcohol, tobacco, and illicit drug prevention: assessing the research evidence.

The problems associated with the use of alcohol, tobacco, and other drugs (ATOD) extract a significant health, social, and economic toll on American society. While the field of substance abuse prevention has made great strides during the past decade, two major challenges remain. First, the field has been disorganized and fragmented with respect to its research and prevention practices; that is, there are often separate ATOD prevention "specialists." Second, both the prevention researchers who test the efficacy of specific prevention strategies and the practitioners who implement prevention efforts often lack an overall perspective to guide strategy selection. To address these limitations, we present an ATOD causal model that seeks to identify those variables (Domains) that are theoretically salient and empirically connected across alcohol, tobacco, and illicit drugs. For the researcher, the model demonstrates important commonalities, as well as gaps, in the literature. For the practitioner, the model is a means to recognize both the complexity of the community system that produces ATOD problems and the multiple intervention points that are possible within this system. Researchers and practitioners are thus challenged to work synergistically to find effective and cost-effective approaches to change or reduce ATOD use and associated problems.

Advertising↗

PubMedDate not supplied

Widowhood and well-being: an examination of sex differences within a causal model.

National survey data (NCOA/Harris and Associates, 1974) are analyzed in a causal model to discern differences in the effects of widowhood on the well-being of older men and women. Based on previous research on mental illness, mortality differentials, and the quality of life, it is hypothesized that widowhood has an adverse impact on well-being, and that this relation is stronger for men than women. While the data support an overall decline in well-being of persons who are widowed, a direct effect of widowhood is substantial only for the negative dimension of the well-being of women. Widowed persons experience lower levels of well-being largely because they tend to be older, in poorer health, and less active in social life than their married counterparts. In the case of widowed women, low economic resources is also a key factor. A consistent pattern of greater reductions in levels of social participation in widowhood for men was not evident.

Affect↗

PubMed1997

The "jump" and "release" effects: some observations on the perception of causality.

Two experiments studied the "release" and "jump" effects. Suppose that--on a homogeneous background--a single object moving on a straight trajectory has a constant physical velocity along all its path except in the middle where this velocity is higher or lower for a short time. The release effect occurs when this velocity is lower and the jump effect when it is higher. In the release effect, the object appears to be released from something that held it back. In the jump effect, the object appears to make a jump forward. In line with Premack's 1990 view, these effects suggest a reclassification of causal phenomena in terms of the perceived origin of the change in movement. This origin is perceived as external in Michotte's launching effect and as both internal and external in the release effect and as internal in the jump effect.

Color Perception↗

PubMed1989

A causal model of mathematics performance in early adolescence: the role of sex.

Using path analysis, the present investigation was done to clarify possible causal linkages among general scholastic aptitude, academic achievement in mathematics, self-concept of ability, and performance on a mathematics examination. Subjects were 122 eighth-grade students who completed a mathematics examination as well as a measure of self-concept of ability. Aptitude and achievement measures were obtained from school records. Analysis showed sex differences in prediction of performance on the mathematics examination. For boys, this performance could be predicted from scholastic aptitude and previous achievement in mathematics. For girls, performance only could be predicted from previous achievement in mathematics. These results indicate that the direction, strength, and magnitude of relations among these variables differed for boys and girls, while mean levels of performance did not.

Achievement↗

PubMed1992

Effects of narcissistic personality organization on causal attributions.

The present study addressed a central, although neglected, aspect of research into narcissism and attributions, the role of cognitive-perpetual processes and cognitive styles of individuals with narcissistic personality disorder in their causal explanation of events. The extent to which narcissistic personality organization may be a determinant of attributional style was examined. The sample consisted of 20 individuals with narcissistic personality disorders and 20 with neurotic disorders. Participants completed the Narcissistic Personality Inventory-40 and the Attributional Style Questionnaire. A significant association between narcissistic personality disorder and internal, stable attributions for positive outcomes was observed. The reformulated learned helplessness model of depression was used to interpret the attributional style of the narcissists as means to obliterate experience of helplessness. The results are discussed in terms of the role of self-esteem and maintenance of self-presentation in the skewed attributional biases of narcissists.

Adult↗

PubMed1993

Causal attributions and coronary heart disease in women.

The relationship between coronary heart-disease endpoints and attributional style in women has been previously unexamined. This study examined the attributions of 73 postmyocardial infarction (MI) women about their heart disease and explored the relationship between attributions and nonfatal coronary recurrence. Women's primary causal attributions included personal behavior (9.6%), blaming others (19.3%), stress (28.8%), luck (12.3%), and family history (13.7%). The largest proportion of recurrences occurred in women attributing their infarcts to marital problems. Of the attributional ratings, ascriptions involving spouses were the only attributions that met entry criteria for logistic regression (p = .019) after controlling for severity of first infarction.

Arousal↗

PubMed1994

Cross-validating a causal model relating attributional style, self-esteem, and depression: an heuristic study.

Pillow, West, and Reich, using path analysis in 1991, were unable to confirm the causal model predicted from the reformulated learned helplessness theory of Abramson, Seligman, and Teasdale which links the dimensions of attributional style with self-esteem and depression. Because their failure to confirm the model may have been due to their using normal subjects instead of psychiatric patients, the model was retested in the present study on psychiatric patients, many of whom had been diagnosed as depressed. Although the Abramson, et al. model was once again not confirmed, neither was the alternative model proposed by Pillow, et al. The model that fitted the data best in this study differed from both of these models and indicated that all three attributional dimensions affect depression solely through the mediation of self-esteem.

Adult↗

PubMed1994

Causal attribution and affective response as mediated by task performance and self-acceptance.

Predictions derived from cognitive consistency theories, self-esteem theories, and ego-serving-bias theory concerning how students would make attributional and affective responses to their academic performance were investigated. 202 university students completed a measure of self-acceptance of their college ability and made attributional and affective responses to an hypothetical examination performance. Analyses showed that students receiving positive feedback perceived greater internal causality and responded with greater positive affect than students receiving negative feedback. Self-acceptance did not moderate the attributions or affective reactions. The results supported the ego-serving-bias theory and provided partial support for self-esteem theory. Findings did not support predictions from cognitive-consistency theory.

Adult↗

PubMed1997

Narcissism and causal attribution.

This study examined the relationship between scores on narcissistic personality traits and causal attributions to positive and negative events. 119 undergraduate students in psychology as participants completed the Narcissistic Personality Inventory-40, the Attributional Style Questionnaire, and several Self-referencing Closed-ended Vignettes. Analyses indicated that men who scored higher on the Narcissistic Personality Inventory-40 made more internal and stable attributions to positive events and more external and unstable attributions to negative events than did men who scored lower on the Narcissistic Personality Inventory-40. Also scores on the Self-referencing Closed-ended Vignettes correlated significantly and positively with the Attributional Style Questionnaire, providing evidence for the validity of the vignettes.

Adolescent↗

PubMed1997

Political identification and perceptions of homelessness: attributed causality and attitudes on public policy.

The study investigated relationships between political orientation, causal perceptions of poverty, and attitudes toward government programs for the poor. The test sample of 200 women and 200 men were recruited from introductory psychology classes. In support of hypotheses based on previous research and Weiner's attribution-emotion-action theory, when compared with self-identified Democrats, self-identified Republicans (a) were significantly more inclined to attribute homelessness to internal vs external factors and (b) expressed significantly less favorable attitudes toward publically funded programs for the homeless. Sex differences were nonsignificant. Conceptual-empirical and methodological implications are discussed. Limitations on inferences from these data and directions for inquiry into the development of individual difference in political cognitions and public policy attitudes are considered.

Adult↗

PubMed1989

Self-serving biases in causal attributions as a function of altered activation asymmetry.

The method of induced lateral orientation of attention was selectively used to alter the balance of activation of the brain toward one cerebral hemisphere or the other. The goal was to extend earlier research which showed greater personal optimism for future events during left hemisphere activation to the related phenomenon of causal attributions. As predicted, there was significantly greater self-serving bias (attribution of internal, stable, and global causes for positive events and external, unstable, and specific causes for negative events) during left hemisphere than during right hemisphere relative activation. This was true for achievement but not for affiliation events. These effects were explained in terms of the increased positive affect which correlates with greater left hemisphere activation. Selective activation of the left hemisphere as a means temporarily to alter attributional style was discussed as a possible tool in the treatment of learned helplessness and depression.

Adolescent↗

PubMed1979

Testing a causal model of environmental influences on the early drug involvement of inner city junior high school youths.

The present study examines a causal model explaining inner city youths' drug involvement using environmental variables which previously have been investigated singly or in various combinations and shown to influence drug use: the availability of drugs in the neighborhood and at school, a view of the neighborhood as tough, the esteem given to drug using, gang-involved persons by peers, friends' substance use, and participation in drug/street culture spare-time activities. The results show friends' use of alcohol and marijuana and participation in drug/street culture out-of-school activities have strong direct effects on personal drug involvement for the Black and Puerto Rican junior high school males and females who were studied; further, friends' use of alcohol and marijuana and the status peers give to drug using, gang-involved persons have respectable indirect effects on drug involvement for the four groups. In addition to these common features, a number of differences in the factors relating to drug involvement are found in the four groups. Implications of the results for alternative methods of drug abuse prevention and treatment are discussed, as is the necessity of utilizing an environmental, sociocultural view of drug use to adequately explain youth drug taking.

Adolescent↗