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At least 19 recordsLinked to original sources

Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship.

The causal relationship between iron deficiency and physical work capacity is evaluated through a systematic review of the research literature, including animal and human studies. Iron deficiency was examined along a continuum from severe iron-deficiency anemia (SIDA) to moderate iron-deficiency anemia (MIDA) to iron deficiency without anemia (IDNA). Work capacity was assessed by aerobic capacity, endurance, energetic efficiency, voluntary activity and work productivity. The 29 research reports examined demonstrated a strong causal effect of SIDA and MIDA on aerobic capacity in animals and humans. The presumed mechanism for this effect is the reduced oxygen transport associated with anemia; tissue iron deficiency may also play a role through reduced cellular oxidative capacity. Endurance capacity was also compromised in SIDA and MIDA, but the strong mediating effects of poor cellular oxidative capacity observed in animals have not been demonstrated in humans. Energetic efficiency was affected at all levels of iron deficiency in humans, in the laboratory and the field. The reduced work productivity observed in field studies is likely due to anemia and reduced oxygen transport. The social and economic consequences of iron-deficiency anemia (IDA) and IDNA have yet to be elucidated. The biological mechanisms for the effect of IDA on work capacity are sufficiently strong to justify interventions to improve iron status as a means of enhancing human capital. This may also extend to the segment of the population experiencing IDNA in whom the effects on work capacity may be more subtle, but the number of individuals thus affected may be considerably more than those experiencing IDA.

Algorithms↗

Investigation of the causal relationship between tracheotomy and aspiration in the acute care setting.

OBJECTIVE: To investigate the causal relationship, if any, between tracheotomy and incidence of aspiration in the acute care setting. STUDY DESIGN: Prospective, consecutive. PATIENTS AND METHODS: Twenty adult patients evaluated between February 1997 and October 1999 participated. Criteria for inclusion were a dysphagia evaluation before tracheotomy, subsequent tracheotomy and placement of a tracheotomy tube, and then a repeat dysphagia evaluation after tracheotomy prior to decannulation. This permitted the causal relationship between tracheotomy and incidence of aspiration to be investigated. Differences between duration of tracheotomy placement and age were analyzed with the Student t test and for non-parametric nominal data the chi2 test was applied. RESULTS: No causal relationship between tracheotomy and aspiration was exhibited, as 19 of 20 (95%) subjects exhibited the same aspiration status before and after tracheotomy. All 12 (100%) subjects who aspirated before tracheotomy also aspirated after tracheotomy and 7 of 8 (88%) subjects who did not aspirate before tracheotomy also did not aspirate after tracheotomy (P > .05). In addition, no significant differences were observed between aspiration status and days since tracheotomy or age (P > .05). CONCLUSION: In the acute care setting, no causal relationship between tracheotomy and aspiration status was exhibited.

Adult↗

Human agency and associative learning: Pavlovian principles govern social process in causal relationship detection.

Estimates of a worker's causal relationship (CR) to production obeyed associative principles, despite the participants' a priori beliefs that workers are responsible or "at cause" for production. In three experiments, social analogues of conditioned stimuli (workers) and unconditioned stimuli (company production information) were manipulated in familiar Pavlovian paradigms. The findings included (1) CR acquisition, (2) unconditioned stimulus-intensity effects, and (3) CR blocking. The research plan employed an approach that Neal Miller (1959) termed "extension of liberalized S-R theory" and drew on the Rescorla-Wagner model to integrate the experimental results, to illuminate the empirical data of social attribution research, and to guide the study of causal relationship detection using social stimuli.

Adult↗

Causal relationship between frailty and diabetes subtypes: A bidirectional Mendelian randomization study.

Frailty and diabetes mellitus (DM) are closely linked, but their causal relationship remains unclear. This study aims to determine the bidirectional causal relationship between frailty and different DM subtypes using Mendelian randomization (MR). We performed a 2-sample MR analysis using summary statistics from large-scale genome-wide association studies. The inverse-variance weighting method was the primary analytical approach, with MR-Egger regression and weighted median methods for sensitivity analysis. Horizontal pleiotropy and heterogeneity were assessed using MR-PRESSO and Cochran Q test. Genetically predicted frailty was significantly associated with an increased risk of type 2 diabetes (T2DM) and gestational diabetes (GDM) (odds ratio [OR]&#x2005;=&#x2005;2.142, 95% confidence interval [CI]: 1.751-2.621, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;2.280, 95% CI: 1.368-3.800, P&#x2005;=&#x2005;.002), but no causal relationship was observed for type 1 diabetes or glycemic traits (P&#x2005;>&#x2005;.05). Conversely, genetically predicted type 1 diabetes, T2DM, GDM, and postprandial glucose levels (2-hour post-load glucose) increased the risk of frailty (OR&#x2005;=&#x2005;1.026, 95% CI: 1.014-1.038, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;1.046, 95% CI: 1.033-1.058, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;1.068, 95% CI: 1.040-1.096, P&#x2005;<&#x2005;.001; OR&#x2005;=&#x2005;1.095, 95% CI: 1.049-1.144, P&#x2005;<&#x2005;.001). Sensitivity analyses confirmed the robustness of these findings. This study provides genetic evidence supporting a bidirectional causal relationship between frailty and diabetes, particularly T2DM and GDM. These findings highlight the need for early frailty screening in diabetic patients and better metabolic management in frail populations.

Humans↗

Path analysis: a strategy for investigating multivariate causal relationships in communication disorders.

This tutorial paper explains, illustrates, and discusses path analysis, a powerful strategy for examining the plausibility and degree of causal relationships which are postulated to exist among a set of variables. In addition to its strength as a method of theory testing, path analysis is highly compatible with the kind of retrospective research which is so often used to study speech and language pathologies. One of its major advantages is that it allows explicit recognition of multiple, interacting causes of communication disorders and allows the researcher to evaluate the logical consequences of assumptions made about the specific nature of those causal relationships. A summary of the meaning of causal relationships is followed by a presentation of the principles underlying path analysis, as well as an outline of its basic procedures. Also presented is an illustrative example of the application of path analysis to the evaluation of some competing causal theories of a communication disorder. Finally, the general advantages of path analysis and its applicability to the investigation of causal relationships in speech and language pathologies are summarized and discussed.

Humans↗

Causal relationship between albumin, total protein, and colorectal cancer risk: A 2-sample Mendelian randomization study.

Albumin (ALB) and total protein (TP) are vital constituents of the blood, and their levels and roles in the risk of colorectal cancer (CRC) are of significance. Previous observational studies have reported correlations among ALB, TP, and CRC. However, the existence of a causal relationship between ALB and CRC in European populations has not been adequately investigated and the causal link between TP and CRC remains unexplored. To address these gaps, we applied Mendelian randomization (MR) to investigate the potential causal relationship between ALB, TP, and CRC. Two-sample MR analysis was used to investigate whether there was a causal relationship between ALB, TP, and CRC. Our exposure data were extracted from genome-wide association study (GWAS) databases sourced from the UK Biobank, containing 315,268 and 314,921 Europeans participants for ALB and TP analyses, respectively. Single nucleotide polymorphisms that were significantly associated with ALB and TP were assessed using GWAS datasets. Our data were derived from the FinnGen Consortium CRC GWAS, which contained 6509 CRC cases and 28,7137 controls. Causal inference between ALB, TP, and CRC was performed using 3 MR methods: inverse variance weighting (IVW), MR-Egger, and weighted median. The IVW analysis showed no significant causal association between ALB and CRC (OR&#x2005;=&#x2005;1.04, 95% CI&#x2005;=&#x2005;0.89-1.21, P&#x2005;=&#x2005;.65). In contrast, the IVW analysis for TP and CRC showed a significant causal association (OR&#x2005;=&#x2005;0.78, 95% CI&#x2005;=&#x2005;0.66-0.92, P&#x2005;=&#x2005;.003), suggesting a reduced risk of CRC. Through a 2-sample MR study investigating the causal relationship between ALB, TP, and CRC in a European population, our findings revealed a significant causal relationship between TP and a reduced risk of CRC.

Humans↗

Using path analysis to examine causal relationships among balanced scorecard performance indicators for general hospitals: the case of a public hospital system in Taiwan.

Examining whether the causal relationships among the performance indicators of the balanced scorecard (BSC) framework exist in hospitals is the aim of this article. Data were collected from all twenty-one general hospitals in a public hospital system and their supervising agency for the 3-year period, 2000-2002. The results of the path analyses identified significant causal relationships among four perspectives in the BSC model. We also verified the relationships among indicators within each perspective, some of which varied as time changed. We conclude that hospital administrators can use path analysis to help them identify and manage leading indicators when adopting the BSC model. However, they should also validate causal relationships between leading and lagging indicators periodically because the management environment changes constantly.

Delivery of Health Care↗

Is there a causal relationship between the receipt of blood transfusions and the development of chronic lung disease of prematurity?

The number and total volume of blood transfusions received by premature babies is, after gestational age and birth weight a good predictor of the likelihood of developing chronic lung disease of prematurity (CLD) and retinopathy of prematurity (ROP). Oxidative damage, inflammation and pulmonary infections are also strongly associated with the development of CLD. It is currently not clear whether there is a causal relationship between the receipt of blood transfusions and oxidative damage, infection, inflammation and CLD in these babies. Strong arguments may be made both for and against a causal relationship. The babies who receive blood transfusions are usually smaller than those who do not, and are ventilated, often with high oxygen levels, for a longer period of time. The longer the baby is on a ventilator the more likely it is to develop pulmonary infection and inflammation. All these factors will promote free radical production and oxidative damage irrespective of the receipt of blood transfusion. This would argue against a causal relationship. On the other hand, an argument may be presented which is based on iron promoted free radical generation, infection and fibrosis consequent to the breakdown of haeme released from transfused erythrocytes. Haeme is broken down by haeme oxygenase (HO) to iron, CO and bilirubin. Under normal circumstances the products of HO activity are beneficial to the organism, but when HO activity is excessive, the products are potentially damaging. Free iron, (in the Fe2+ form) if not sequestered with protein or urate, will generate highly toxic free radicals via the Fenton and Heber-Wiess reactions, predispose the tissue to infection and promote fibrosis. The iron chelating ability of the premature baby appears to be limited so that it would be difficult to deal with any increase in free iron production. Free iron will in turn induce HO activity leading to a potentially serious positive feedback process. The lung is particularly sensitive to iron induced HO activity. In addition, HO activity may be enhanced by other events occurring in the premature lung such as the production of proinflammatory cytokines and the reduced level of glutathione. Thus, the possibility of a causal relationship clearly exists and needs to be examined. This can be attempted by measuring the products of HO activity in relation to the receipt of blood transfusions.

Chronic Disease↗

Scleroderma and augmentation mammoplasty--a causal relationship?

BACKGROUND: The studies implicating a causal relationship between silicone and scleroderma, other autoimmune disease, and fibromyalgia-like symptoms have been largely descriptive with absence of appropriate controls and no consideration of potential confounders. This case control study of augmentation mammoplasty and scleroderma represents an attempt to answer these deficiencies. AIMS: To compare the frequency and temporal relationship of augmentation mammoplasty in interviewed and deceased cases and interviewed controls. To determine the frequencies of exposure to non-augmentation mammoplasty silicone, and to determine the frequencies of mastectomy and breast lumpectomy in interviewed cases and controls. METHODS: Scleroderma cases and age-stratified general practice controls were interviewed using a prepilotted telephone questionnaire. Self-reported date/s of augmentation mammoplasty were ascertained, as were dates of onset of first and second scleroderma symptom/s and scleroderma diagnosis, where relevant. Comparison of socioeconomically adjusted rates was expressed in terms of rate ratios. RESULTS: Augmentation mammoplasty rates were comparable between interviewed cases and controls. No augmentation mammoplasty procedures were documented in deceased scleroderma patients' medical records. Rates of exposure to non-mammoplasty silicone, mastectomy and breast lumpectomy were comparable in interviewed cases and controls. CONCLUSIONS: This study failed to demonstrate an association between silicone breast implantation and the subsequent development of scleroderma, to a relative risk level as low as 4.5 with 90% power.

Adult↗

Causal relationship between cannabis use and psychotic symptoms or depression. Should we wait and see? A public health perspective.

The aim of this paper is to update and critically analyze the public health relevance of available evidence about the causal relationship between cannabis use and psychosis or depression. There are conflicting views about this causal relationship. Two systematic reviews of existing evidence assessed this association and were published in 2004, but they came to different conclusions. From a public health perspective a thorough discussion is warranted before attributing any observed effect to potential biases. First, the impact of residual confounding in this causal relationship is discussed. We consider that the attenuation of estimates after controlling for confounding factors cannot be interpreted as evidence to support the claim that residual confounding fully explains this link. Secondly, taking into account the results of recent studies, the time-sequence and dose-response criteria of causality are discussed. The fact that unreported or subclinical psychological problems might have preceded and precipitated cannabis use is a very unlikely explanation when the cannabis-psychosis outcome link is assessed from different longitudinal studies. And finally, available evidence is interpreted with a broad view of public health and by taking into account the precautionary principle. We therefore provide reasons to support the case that stronger preventive actions against cannabis are still required in order to avoid the potential increased incidence of psychosocial health problems in the future.

Depression↗

Plasma metabolites mediate the causal relationship between gut microbiota and erectile dysfunction: insights from Mendelian randomization study.

BACKGROUND: While the relationship between gut microbiota and erectile dysfunction (ED) has been reported, the specific pathways involved remain unclear. AIM: This study aims to investigate the causal relationship between gut microbiota and ED, and to identify the potential role of plasma metabolites as mediators. METHODS: Utilizing aggregated genome-wide association study (GWAS) data, a comprehensive two-sample Mendelian randomization (MR) analysis was performed involving 196 gut microbiota taxa, 1400 plasma metabolites and ED. Causal relationships between gut microbiota, plasma metabolites and ED were explored. In addition, mediation analysis was applied to identify the pathway from gut microbiota to ED mediated by plasma metabolites. OUTCOMES: This study reveals that plasma metabolites act as mediators regulating the influence of gut microbiota on ED. RESULTS: MR analysis identified causal relationships between six gut microbial taxa and ED, with Butyrivibrio increasing the risk of ED, while Alistipes, Prevotella 9, Dialister, Marvinbryantia, and LachnospiraceaeUCG010 exhibited protective effects. Additionally, 45 plasma metabolites demonstrated causal associations with ED. Finally, mediation analysis revealed four mediation relationships. Sensitivity analysis indicated no heterogeneity or pleiotropy in this study. CLINICAL IMPLICATIONS: Modulating gut microbiota or targeting specific metabolites may offer new therapeutic approaches for ED, highlighting the potential for microbiome-based interventions. STRENGTHS AND LIMITATIONS: The MR approach and large-scale GWAS data provide robust causal evidence, but the findings are limited by their focus on European populations and lack of experimental validation. Further studies are needed to confirm these mechanisms in diverse cohorts and functional models. CONCLUSION: This study establishes a causal link between gut microbiota, plasma metabolites, and ED, identifying specific microbial taxa and metabolites as key contributors to ED risk. The mediating role of plasma metabolites highlights potential therapeutic strategies, such as probiotics or dietary interventions targeting harmful metabolites.

Mendelian randomization↗

[Assessment of causal relationship in work-related pulmonary diseases. An epidemiological approach].

A competent assessment of causal relationships in the case of work-related lung disorders depends on correct diagnosis, a detailed occupational history and updated epidemiological knowledge about causal relationships, obtained from the literature. Assessments for purposes of compensation demand, in addition, an explicit choice of methods for calculating causes, before a meaningful attempt can be made to weight the various factors in and outside the working environment. If adequate epidemiological knowledge is available, the causal probability, based on the etiological fraction among the exposed persons (attributable risk) may be a useful tool for apportioning the different causal factors.

Disability Evaluation↗

Menière's symptoms resulting from bilateral otosclerotic occlusion of the endolymphatic duct: an analysis of a causal relationship between otosclerosis and Menière's disease.

An association between otosclerosis and Menière's disease has been proposed on both a clinical and temporal bone histopathologic basis for well over three-quarters of a century. Controversy persists over a causal relationship between these two entities, however, and the underlying pathophysiologic mechanisms relating capsular otosclerosis with Menière's disease remain speculative. The first case of total, bilateral endolymphatic duct occlusion resulting from extensive capsular otosclerosis is presented in a woman manifesting Menière's symptoms. The severe endolymphatic hydrops resulting from otosclerotic endolymphatic duct occlusion is given as histopathologic proof of a causal relationship between these two entities. Analysis of 18 of our own temporal bone cases of extensive capsular otosclerosis without endolymphatic hydrops and review of the literature indicates the uniqueness of such a firm causal relationship in the present case.

Adult↗

On doing the "impossible": inferring that a putative causal relationship does not exist.

A simple heuristic is proposed for drawing a warranted inference that a causal relationship does not exist between two events. It is illustrated by a study of the putative indirect causal relationship between Autistic Disorder and the Fragile X syndrome. This study was designed to ensure that a failure to find such a relationship provided good reasons for concluding that it was unlikely there was a relationship between Autistic Disorder and the Fragile X syndrome.

Autistic Disorder↗

Elucidation of causal relationships for multi-sourced activities in the human brain by directed transinformation between time series of equivalent dipoles.

Visualizing the causal relationships among multi-sourced activities in the human brain non-invasively is important for the elucidation of the processing mechanism and for clinical application of the diagnosis of disease. We will show our preliminary results of estimating equivalent dipoles to show the multi-sourced brain activities and analyse directed transinformation through time series of dipoles with three-dimensional display. First, we estimated the equivalent dipoles from evoked potentials via a three-layered concentric spherical model and two-dipole estimation. Second, we analysed the directed transinformation between two time series of the first and second dipole moments by use of the derived two dipole positions and moments as the loci and magnitude of brain activities. Therefore, we obtained bi-directional information flow between the neuronal activities localized in three-dimensional space of the brain with respect to 21-ch somatosensory evoked potentials (SEPs). Our preliminary results can be interpreted as showing that the information, calculated based on our method, flows from the first dipole cluster located in the thalamus, to the second dipole cluster located in the somatosensory area. This does not go against the neurophysiological knowledge of SEPs that the activities move from the thalamus to the somatosensory area. With the above, we show the potential possibility of realizing the elucidation of causal relationships.

Action Potentials↗

Causal relationship between white matter structural connectivity and epilepsy.

White matter structural connectivity has recently been linked to epilepsy pathogenesis, yet its causal role remains unclear. This study used Mendelian randomization (MR) to investigate the causal relationship between white matter structural connectivity and epilepsy. GWAS summary statistics for white matter structural connectivity were sourced from the UK Biobank, while epilepsy data were obtained from FinnGen R10 and the International League Against Epilepsy (ILAE). Our MR analysis revealed significant causal links between white matter structural connectivity and epilepsy risk. Increased connectivity between the right hemisphere visual and salience/ventral attention networks (RH Vis to RH Sal/VentAttn WMSC) was associated with higher epilepsy risk in FinnGen_R10_FE_STRICT (OR&#xa0;=&#xa0;2.25, 95&#xa0;% CI&#xa0;=&#xa0;1.43-3.56, p&#xa0;<&#xa0;0.01, FDR P&#xa0;=&#xa0;0.019). Conversely, increased connectivity between left and right hemisphere salience/ventral attention networks (LH Sal/VentAttn to RH Sal/VentAttn WMSC) was linked to reduced epilepsy risk in FinnGen_R10_GE_STRICT (OR&#xa0;=&#xa0;0.17, 95&#xa0;% CI&#xa0;=&#xa0;0.07-0.46, p&#xa0;<&#xa0;0.01, FDR P&#xa0;=&#xa0;0.033). A total of 15 nominally significant associations were identified across datasets. These findings suggest a causal relationship between white matter structural connectivity and epilepsy, offering insights into disease mechanisms and potential therapeutic targets.

Humans↗

[The causal relationship].

Only the controlled trial method, clinical equivalent to the experimental method, with its successive phases and randomization, is able to confirm a real causal relationship and quantify the risk of error (alpha). However, the study must have sufficient power and randomization must not have resulted in an unbalanced distribution of various parameters likely to influence the result. Other methods, particularly surveys and case studies, only provide presumptions of causality. This review article, illustrated by three examples from the urological literature, is designed to demonstrate the difficulties of establishing a causal relationship when possible biases and confounding factors are taken into account.

Causality↗

Causal relationships between antibody-mediated immune responses and acute pancreatitis: Evidence from a genetic study.

Certain specific antibody-mediated immune responses may be associated with acute pancreatitis (AP), but their causal relationship remains uncertain. Therefore, we used bidirectional two-sample Mendelian randomization (MR) to investigate their causal link and potential mediation by inflammatory cytokines. Data for this study were sourced from a large-scale Genome Wide Association Study (GWAS) communal data pool. To explore the causality between antibody-mediated immune responses and AP, we performed two-sample bidirectional MR analyses using 5 approaches: inverse-variance weighted (IVW), MR-Egger, weighted mode, weighted median, and simple mode. We also studied the potential mediating effect of 91 circulating inflammatory cytokines using a two-step MR method. Additionally, sensitivity analyses were conducted using MR-Egger intercept test and Cochran Q test to ensure the robustness of the outcomes. The results of forward MR analysis showed that anti-Epstein-Barr virus (anti-EBV) IgG seropositivity [OR&#x2005;=&#x2005;0.941; 95% CI, 0.893-0.992; P&#x2005;=&#x2005;.023] and human herpes virus (HHV) 6 IE1A antibody levels [OR&#x2005;=&#x2005;0.894; 95% CI, 0.816-0.981; P&#x2005;=&#x2005;.017] significantly reduced the risk of AP. The results of the reverse MR analysis revealed a negative correlation between AP and anti-EBV IgG seropositivity [OR&#x2005;=&#x2005;0.775; 95% CI, 0.605-0.992; P&#x2005;=&#x2005;.043]. Furthermore, none of the 91 circulating inflammatory cytokines could mediate the causal relationship between HHV-6 IE1A antibody levels and the risk of AP. The results of sensitivity analysis confirmed the robustness of these causalities. The current study suggests that HHV-6 IE1A antibody levels are a protective factor against AP, and there is a bidirectional causality between AP and anti-EBV IgG seropositivity. In addition, the mediation analysis results showed that the 91 circulating inflammatory cytokines could not serve as mediators between the 46 antibody-mediated immune responses and AP.

Humans↗