A reader's guide to the evaluation of prognostic studies

In this article, we review guidelines which may be used to evaluate studies documenting prognosis. We describe a clinical problem involving the prognosis of a patient in an intensive care unit. An approach to the literature search is then outlined. The results of the literature search are described and criteria for the appraisal of articles describing prognosis and prognostic factors are discussed using one article as an example.     

Agents, vehicles, and causal inference in bacterial foodborne disease outbreaks: 82 reports (1986-1995)

OBJECTIVE: To examine the study design of, and the practice of causal inference in, investigations of bacterial foodborne disease outbreaks occurring in the United States and to summarize agents and vehicles identified. DESIGN: Retrospective study. PROCEDURE: An online medical reference database was searched for reports of bacterial foodborne disease outbreak investigations published between 1986 and 1995. Reports were retrieved and reviewed for use of 9 causal criteria in investigations. Information on etiologic agents, vehicles, seasonality, and primary study design from each outbreak was also retrieved. RESULTS: 82 reports were retrieved and reviewed. Coherence, consistency, temporality, and strength of association were the causal criteria most commonly used in foodborne disease outbreak investigations. Coherence was used in all investigations. The number of criteria used ranged from 3 to 7. Meat (n = 20) and eggs (12) were the most commonly implicated vehicles. Salmonella sp and Escherichia coli O157:H7 accounted for 55% of agents reportedly isolated. Cohort and case-control methods were the most common study designs. CLINICAL RELEVANCE: Patterns were found in the use of causal criteria in foodborne disease outbreak investigations. These criteria can provide veterinarians and other public health practitioners with a means to effectively conceptualize, communicate, and summarize causal conclusions. The 4 most commonly used criteria may represent core criteria that investigators consider most useful in explaining food-borne disease outbreaks.     

Causal inference and related statistical methods

Statistical approaches for evaluating causal effects and for discovering causal networks are discussed in this paper.A causal relation between two variables is different from an association or correlation between them.An association measurement between two variables and may be changed dramatically from positive to negative by omitting a third variable,which is called Yule-Simpson paradox.We shall discuss how to evaluate the causal effect of a treatment or exposure on an outcome to avoid the phenomena of Yule-Simpson paradox. Surrogates and intermediate variables are often used to reduce measurement costs or duration when measurement of endpoint variables is expensive,inconvenient,infeasible or unobservable in practice.There have been many criteria for surrogates.However,it is possible that for a surrogate satisfying these criteria,a treatment has a positive effect on the surrogate,which in turn has a positive effect on the outcome,but the treatment has a negative effect on the outcome,which is called the surrogate paradox.We shall discuss criteria for surrogates to avoid the phenomena of the surrogate paradox. Causal networks which describe the causal relationships among a large number of variables have been applied to many research fields.It is important to discover structures of causal networks from observed data.We propose a recursive approach for discovering a causal network in which a structural learning of a large network is decomposed recursively into learning of small networks.Further to discover causal relationships,we present an active learning approach in terms of external interventions on some variables.When we focus on the causes of an interest outcome, instead of discovering a whole network,we propose a local learning approach to discover these causes that affect the outcome.     

Impact of anesthesia on the cognitive functioning of the elderly

Exposure to general anesthesia has been suggested as a possible cause of long-term cognitive impairment in elderly subjects. The present study reviews the literature in this field in order to describe postoperative cognitive impairment in elderly populations, to determine to what extent this may be attributed to anesthetic agents, and to consider evidence of a causal relationship between anesthesia and onset of senile dementia. A systematic literature search was conducted using five bibliographic databases (PASCAL, Medline, Excerpta Medica, Psychological Abstracts, and Science Citation Index). Significant cognitive dysfunction was found to be common in elderly persons 1 to 3 days after surgery, but reports of longer-term impairment are inconsistent due to the heterogeneity of the procedures used and populations targeted in such studies. Incidence rates vary widely according to type of surgery, suggesting that factors other than anesthesia explain a significant proportion of the observed variance. Anesthesia appears to be associated with longerterm cognitive disorder and the acceleration of senile dementia, but only in a small number of cases, suggesting the existence of other interacting etiological factors.     

Relationship between estrogen levels, use of hormone replacement therapy, and breast cancer

We sought to determine the strength of the evidence suggesting that estrogen and postmenopausal replacement hormones play a role in the development of breast cancer. We reviewed the existing English language literature in MEDLINE on hormones and breast cancer, including reports on cell proliferation and endogenous hormone levels, as well as epidemiologic studies of the relationship between the use of postmenopausal hormones and the risk of breast cancer in women. A factor that increases the probability that cancer will develop in an individual has been defined as a cancer cause. The Hill criteria for demonstrating a link between environmental factors and disease were used to review the evidence for a causal relationship between female hormones and breast cancer. We found evidence of a causal relationship between these hormones and breast cancer, based on the following criteria: consistency, dose-response pattern, biologic plausibility, temporality, strength of association, and coherence. The magnitude of the increase in breast cancer risk per year of hormone use is comparable to that associated with delaying menopause by a year. The positive relationship between endogenous hormone levels in postmenopausal women and risk of breast cancer supports a biologic mechanism for the relationship between use of hormones and increased risk of this disease. The finding that the increase in risk of breast cancer associated with increasing duration of hormone use does not vary substantially across studies offers further evidence for a causal relationship. We conclude that existing evidence supports a causal relationship between use of estrogens and progestins, levels of endogenous estrogens, and breast cancer incidence in postmenopausal women. Hormones may act to promote the late stages of carcinogenesis among postmenopausal women and to facilitate the proliferation of malignant cells. Strategies that do not cause breast cancer are urgently needed for the relief of menopausal symptoms and the long-term prevention of osteoporosis and heart disease.     

Refining hollow obturator base using light-activated resin

Inclusion body myositis (IBM) is a separate class of the inflammatory myopathies with recently proposed clinical and pathological diagnostic criteria. An association between inflammatory myopathies and malignancy has been questioned in the literature. Recent reviews of the inflammatory myopathies suggest that only dermatomyositis is associated with malignancy. The largest study to date of patients with IBM found that 15% had a malignancy (6 of 40). We report the first documented case of IBM and concurrent transitional cell carcinoma of the bladder. We suggest that a causal relationship between IBM and malignancy may exist because of significantly improved functional strength gained after tumor removal.     

Elevated CEA in breast cancer patients with overlooked medullary thyroid carcinoma

After mastectomy and radiation for breast cancer, two patients were found to have persistent elevated CEA in their serum. This finding was erroneously attributed to occult metastases for the first patient and to local recurrence for the second. Overlooked medullary thyroid carcinoma (MTC) was the causal disease in both patients. A review of the literature stresses the frequency of CEA elevation in serum of MTC patients. A thorough search for any possible cause of elevated levels of CEA is advocated, particularly by thyroid sonogram with a needle aspiration biopsy when a nodule is discovered and by calcitonin assay in the serum.     

The causal role for genital ulcer disease as a risk factor for transmission of human immunodeficiency virus. An application of the Bradford Hill criteria

BACKGROUND AND OBJECTIVES: Genital ulcer disease (GUD) has been reported to increase the risk for the acquisition of human immunodeficiency virus (HIV). Although many investigators have reported an increased risk for HIV infection in persons with concurrent or previous GUD, not all studies have been designed to determine whether GUD causes an increased risk for HIV infection or acts only as a risk marker for infection. The evidence from the literature is discussed, and the criteria for causal inference proposed by Sir Austin Bradford Hill are applied. GOAL: To evaluate the strength of the association between GUD and infection by HIV. STUDY DESIGN: Case-control, cross-sectional, and cohort studies that examined the association between HIV seroconversion and GUD were chosen from the literature. Twenty-seven epidemiologic studies were selected for analysis, many of which reported separate analyses of the association between HIV infection and herpes simplex virus infection, syphilis, or nonspecified GUD. The studies were analyzed to investigate the magnitude of association between GUD and HIV, and the evidence evaluated using Hill's criteria. RESULTS: Approximately two thirds of the analyses reported a statistically significant association between GUD and HIV infection. Fourteen studies reported 29 separate analyses using a case-control design, 18 of which reported a statistically significant association between GUD (GUD, herpes, and syphilis) and HIV infection, four analyses were of varying significance depending on the analytical technique used, and seven were nonsignificant. Thirteen studies reported 23 separate longitudinal analyses that used a nested case-control or cohort design: 11 reported a significant association, 11 had nonsignificant findings, and results of one study varied. No study reported a statistically significant negative association. When applying the literature to Hill's criteria, all nine criteria for causal inference were met, providing additional evidence that genital ulcers are associated with an increased risk for the development of HIV infection. CONCLUSIONS: The published evidence suggests that GUD increases the risk for HIV acquisition. Few studies, however, have examined carefully the temporal association between preexisting GUD and subsequent HIV acquisition. The analyses that simultaneously controlled for additional risks for HIV infection, such as lifetime sex partners or history of injection drug use, report a generally lower risk for HIV associated with GUD. It is likely that studies that adequately control for risk factors will find a lower risk associated with GUD than was reported in the literature earlier in the HIV epidemic. Future research needs and the problems associated with conducting these types of studies are discussed.     

Late-onset multiple sclerosis and serum monoclonal gammopathy: an incidental association?

Four patients older than 45 years with a central nervous system demyelinating disease associated to a monoclonal gammopathy are reported. The neurologic disease met the diagnostic criteria of multiple sclerosis, with the particularity of a late onset. Monoclonal paraproteinemia was also present in the cerebrospinal fluid, associated with an intrathecal immunoglobulin synthesis. The clinical data and the course of the disease were comparable to the previous reports of late onset multiple sclerosis. A causal link between the dysglobulinemia and the neurological disease may not be demonstrated. However, such an association may underline the role of humoral processes in multiple sclerosis.     

Increased general practice workload due to a primary care led National Health Service: the need for evidence to support rhetoric

Recent policy initiatives have focused on shifts in the balance of care from secondary care to primary care. A consequence of such shifts is increased workload in primary care. The aim of this paper is to appraise the literature critically to assess whether changes in the balance of care have led to additional work for general practices. In particular, the implications of this literature for the measurement of workload in general practice are highlighted. After an extensive, systematic literature search, only 12 studies that met the review criteria were identified. Although the studies pointed to negligible effects on the number of general practitioner (GP) visits, they failed to capture the many other attributes of a practice's work that are likely to be influenced by a shift in the balance of care. These include both qualitative (e.g. stress and mental effort) and quantitative (i.e. the use of resources in the practice, such as GPs, nurses and other staff's time and administration) measures of workload. The studies may therefore have under-estimated the effect on practice workload. To identify correctly the impact on workload of shifts in the balance of care, studies evaluating shifts need to improve their measurement of general practice workload. Furthermore, an extended definition of workload needs to be developed and tested, and workload monitored over time.     

Peroxidative and glutathione status in uterus and placenta after normal and pathological pregnancy

The content and amount of the allergologic diagnostic measures differs more and more in comparison to the causal treatment and consulting of the patient during care. The tasks of quality assurance may include the development of criteria for evaluated diagnostic measures and the resulting treatment concepts with respect to an interdisciplinary approach. The cooperation with patient groups should be integrated in such a concept. The basic allergologic care, the interaction with allergologic centers, the supervision and coordination with facilities of in-patient care have to be newly defined in the frame of a structural discussion.     

On problems with the cause–reason distinction in attribution theory.

A. R. Buss's (see record 1980-09652-001) statement on causal and reason explanations of behavior involves a contribution regarding a necessary distinction in attribution theory. In the present paper, it is argued that despite his reformulation of previous analyses of lay attribution, Buss fails to provide substantive guidance for empirically testing the major assumptions of his hypothesized cause–reason distinction. Most important, Buss's analysis does not yield unambiguous theoretical criteria for operationally distinguishing intentional actions and unintentional occurrences and for judging the content of actors' and observers' explanations as causal or reason in nature. Without such specifications, it is concluded that Buss's central ideas may be empirically untestable. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of inference necessity and reading goal on children's inferential generation.

Examined inferential processing during reading. Adults and 3rd, 5th, and 8th graders read stories implying a consequence and answered questions. Some of the inferences were more necessary than others for comprehension according to T. Trabasso and P. Van den Broek's (see record 1987-18271-001) causal criteria, and the readers engaged in either superficial or integrative reading. Results showed that elaborative inferences were not as likely to be generated as those more necessary for comprehension. The necessity manipulation also produced a similar pattern of responding among the 4 groups, suggesting that even the young children were sensitive to the causal criteria. In addition, the integrative reading condition prompted a general slowdown for the 2 younger groups, whereas the 2 older groups were not as affected by reading condition. This pattern was interpreted in terms of differences in attention demands and working memory capacity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contact interactions method: a new algorithm for protein folding simulations

Computer simulations of simple exact lattice models are an aid in the study of protein folding process; they have sometimes resulted in predictions experimentally proved. The contact interactions (CI) method is here proposed as a new algorithm for the conformational search in the low-energy regions of protein chains modeled as copolymers of hydrophobic and polar monomers configured as self-avoiding walks on square or cubic lattices. It may be regarded as an extension of the standard Monte Carlo method improved by the concept of cooperativity deriving from nonlocal contact interactions. A major difference with respect to other algorithms is that criteria for the acceptance of new conformations generated during the simulations are not based on the energy of the entire molecule, but cooling factors associated with each residue define regions of the model protein with higher or lower mobility. Nine sequences of length ranging from 20 to 64 residues were used on the square lattice and 15 sequences of length ranging from 46 to 136 residues were used on the cubic lattice. The CI algorithm proved very efficient both in two and three dimensions, and allowed us to localize energy minima not localized by other searching algorithms described in the literature. Use of this algorithm is not limited to the conformational search, because it allows the exploration of thermodynamic and kinetic behavior of model protein chains.     

The relationship between eating disorder not otherwise specified (EDNOS) and officially recognized eating disorders: Meta-analysis and implications for DSM.

Eating disorder not otherwise specified (EDNOS) is the most prevalent eating disorder (ED) diagnosis. In this meta-analysis, the authors aimed to inform Diagnostic and Statistical Manual of Mental Disorders revisions by comparing the psychopathology of EDNOS with that of the officially recognized EDs: anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). A comprehensive literature search identified 125 eligible studies (published and unpublished) appearing in the literature from 1987 to 2007. Random effects analyses indicated that whereas EDNOS did not differ significantly from AN and BED on eating pathology or general psychopathology, BN exhibited greater eating and general psychopathology than EDNOS. Moderator analyses indicated that EDNOS groups who met all diagnostic criteria for AN except for amenorrhea did not differ significantly from full syndrome cases. Similarly, EDNOS groups who met all criteria for BN or BED except for binge frequency did not differ significantly from full syndrome cases. Results suggest that EDNOS represents a set of disorders associated with substantial psychological and physiological morbidity. Although certain EDNOS subtypes could be incorporated into existing Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) categories, others—such as purging disorder and non-fat-phobic AN—may be best conceptualized as distinct syndromes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Concerns regarding the traditional paradigm for causal research: The unified paradigm and causal research in scientific psychology.

The traditional paradigm refers to the assumption held by most methodologists and researchers that causal research must be defined in terms of the causal powers evident in a closed system. The traditional paradigm does not concord, however, with the nature of scientific theories often cited in the methodological and research literature. The unified paradigm is introduced and causal research defined in terms of the causal powers evident in an open system. Notable implications of the unified paradigm are that experimental methods do not provide a better opportunity than modeling methods to conduct a causal analysis and that the nomenclature often used to describe the validity of causal conclusions must be amended. Additional implications of the unified paradigm are discussed and includes a comparison of the traditional paradigm and the unified paradigm when applied to treatment-outcome research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lambda repressor N-terminal DNA-binding domain as an assay for protein transmembrane segment interactions in vivo

OBJECTIVE: To critically review the English-language literature and describe the current diagnosis, prevalence, etiology, and treatment of antisperm antibodies (ASA). DESIGN: A comprehensive literature search of the English-language literature published between 1966 and December 1997 was performed on MEDLINE. Articles were also located via bibliographies of published works. RESULT(S): Data were excerpted from articles identified by MEDLINE search. The diagnosis, prevalence, etiology, and treatment of ASA are described. CONCLUSION(S): There is sufficient evidence that ASA impair fertility in couples with unexplained infertility. A number of different methodologies are available, which may be used in their detection. However, in many cases, test interpretation is subjective. Although there is not enough evidence to support systemic treatment for ASA, application of a variety of assisted reproductive technologies improves outcome.