Evidence Of Other Risk Factors Research Articles

Environmental Risk Factors for Schizophrenia and Bipolar Disorder and Their Relationship to Genetic Risk: Current Knowledge and Future Directions.

Schizophrenia (SZ) and bipolar disorder (BD) are severe psychiatric disorders which result from complex interplay between genetic and environmental factors. It is well-established that they are highly heritable disorders, and considerable progress has been made identifying their shared and distinct genetic risk factors. However, the 15–40% of risk that is derived from environmental sources is less definitively known. Environmental factors that have been repeatedly investigated and often associated with SZ include: obstetric complications, infections, winter or spring birth, migration, urban living, childhood adversity, and cannabis use. There is evidence that childhood adversity and some types of infections are also associated with BD. Evidence for other risk factors in BD is weaker due to fewer studies and often smaller sample sizes. Relatively few environmental exposures have ever been examined for SZ or BD, and additional ones likely remain to be discovered. A complete picture of how genetic and environmental risk factors confer risk for these disorders requires an understanding of how they interact. Early gene-by-environment interaction studies for both SZ and BD often involved candidate genes and were underpowered. Larger samples with genome-wide data and polygenic risk scores now offer enhanced prospects to reveal genetic interactions with environmental exposures that contribute to risk for these disorders. Overall, although some environmental risk factors have been identified for SZ, few have been for BD, and the extent to which these account for the total risk from environmental sources remains unknown. For both disorders, interactions between genetic and environmental risk factors are also not well understood and merit further investigation. Questions remain regarding the mechanisms by which risk factors exert their effects, and the ways in which environmental factors differ by sex. Concurrent investigations of environmental and genetic risk factors in SZ and BD are needed as we work toward a more comprehensive understanding of the ways in which these disorders arise.

Ten-Year Trend and Correlates of Reported Posttraumatic Stress Disorder among Young Male Veteran Suicide Decedents-Results from the National Violent Death Reporting System, 16 U.S. States, 2005-2014.

This study examined trends and correlates of reported post-traumatic stress disorder (PTSD) among young male Veteran suicide decedents, using data from the National Violent Death Reporting System from 2005-2014 on 1,362 male U.S. Veteran suicide decedents aged 18-34years. Prevalence of reported PTSD (i.e., diagnosis/symptoms) was determined by mental health diagnostic fields and narratives and examined by year. Demographic, incident, and precipitating circumstance characteristics correlated with reported PTSD were identified. One-hundred ninety-eight (15%) decedents had PTSD evidence. A 30-fold increase in reported PTSD prevalence occurred among decedents aged 25-34years; however, no increase was observed among younger decedents. Reported PTSD was associated with past deployments (odds ratio (OR): 14.5, 95% confidence interval (95% CI): 9.0-23.4); depression (OR: 1.8, 95% CI: 1.2-2.6); and divorce (OR: 1.7, 95% CI: 1.0-2.7). Recent crisis (OR: 0.6, 95% CI: 0.3-0.9) was inversely associated with reported PTSD. Reported PTSD prevalence substantially increased among Veteran suicide decedents aged 25-34years suggesting it is beginning to play a larger role in suicide for this group. Few correlated suicide risk factors were found, suggesting that if symptoms of PTSD are present, heightened vigilance by providers for suicide risk might be warranted, irrespective of evidence of other risk factors.

Which Risk Factors Causally Influence Dementia? A Systematic Review of Mendelian Randomization Studies.

Background:Numerous risk factors for dementia are well established, though the causal nature of these associations remains unclear.Objective:To systematically review Mendelian randomization (MR) studies investigating causal relationships between risk factors and global cognitive function or dementia.Methods:We searched five databases from inception to February 2017 and conducted citation searches including MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes. Two reviewers independently assessed titles and abstracts, full-texts, and study quality.Results:We included 18 MR studies investigating education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length. Studies were of predominantly good quality, however eight received low ratings for sample size and statistical power. The most convincing causal evidence was found for an association of shorter telomeres with increased risk of Alzheimer’s disease (AD). Causal evidence was weaker for smoking quantity, vitamin D, homocysteine, systolic blood pressure, fasting glucose, insulin sensitivity, and high-density lipoprotein cholesterol. Well-replicated associations were not present for most exposures and we cannot fully discount survival and diagnostic bias, or the potential for pleiotropic effects.Conclusions:Genetic evidence supported a causal association between telomere length and AD, whereas limited evidence for other risk factors was largely inconclusive with tentative evidence for smoking quantity, vitamin D, homocysteine, and selected metabolic markers. The lack of stronger evidence for other risk factors may reflect insufficient statistical power. Larger well-designed MR studies would therefore help establish the causal status of these dementia risk factors.

A SYSTEMATIC REVIEW OF MENDELIAN RANDOMIZATION STUDIES INVESTIGATING CAUSAL ASSOCIATIONS BETWEEN RISK FACTORS AND DEMENTIA

Very little is known about the causal nature of the associations between established risk factors, e.g. education and smoking and dementia risk. We have therefore conducted a systematic review of Mendelian randomization (MR) studies investigating causal links between risk factors and dementia or dementia-related outcomes. We searched five databases from inception to March 2016 using a search strategy including subject headings and free text terms relevant to dementia, cognition and MR. Forward and backward citation searches of included publications were also conducted. We included MR studies investigating the association between any risk factor and global cognitive function, all-cause dementia or dementia subtypes, excluding non-genetic studies, genetic studies other than MR and animal studies. Two reviewers independently screened titles and abstracts, reviewed full-texts and assessed the quality of included studies. Fourteen MR studies investigating a variety of risk factors (education, lifestyle factors, cardiovascular factors and related biomarkers, diabetes related and other endocrine factors, and telomere length) and dementia-related outcomes met our inclusion criteria. Most studies received an overall rating of good quality, however sample size and statistical power were rated low in half of the studies. Shorter telomeres were causally associated with an increased risk of Alzheimer's disease (AD, odds ratio per standard deviation decrease of telomere length = 1.36 (1.12, 1.67), p = 0.002). There was also some suggestion of a causal association with smoking quantity and metabolic risk factors including systolic blood pressure, fasting glucose, insulin sensitivity and high-density lipoprotein cholesterol. Causal associations between several risk factors and dementia-related outcomes were investigated in one study only. Moreover, survival and diagnostic bias or pleiotropic effects cannot be excluded. There was convincing genetic evidence to support a causal association between telomere length and AD. Inconclusive evidence for other risk factors or tentative evidence for smoking quantity and selected metabolic markers may result from insufficient statistical power. Further well designed MR studies are needed to investigate the causality of the associations between risk factors and dementia where randomised controlled trials are unethical or impractical.

Infections Caused by Vibrionaceae

Vibrionaceae is a bacterial family of motile facultative gram-negative bacilli. Several species can be pathogenic to humans and cause severe disease, especially in patients with risk factors. Vibrio-mediated diseases have been reported worldwide and are usually associated with exposure to brackish or saltwater and seafood. The most common infections depending on the species are gastroenteritis, wound and soft-tissue infections including necrotizing fasciitis, and primary sepsis. The most common risk factors for severe infection include chronic liver disease, diabetes mellitus, malignancy, immunocompromise including HIV infection, iron storage disorders, heart disease including heart failure, and chronic renal failure. Depending on the species, occasional cases of severe infection may occur in immunocompetent patients without evidence of other risk factors. Several antibiotics are usually active against most pathogenic species in both families. Increasing resistance in various locations worldwide has been reported to tetracyclines, trimethoprim-sulfamethoxazole, and ciprofloxacin especially for toxigenic Vibrio cholerae.

Multi-Dimensional Risk Factor Patterns Associated with Non-Use of Highly Active Antiretroviral Therapy among Human Immunodeficiency Virus-Infected Women

Objectives Relationships between non-use of highly active antiretroviral therapy (HAART), race/ethnicity, violence, drug use, and other risk factors are investigated using qualitative profiles of five risk factors (unprotected sex, multiple male partners, heavy drinking, crack, cocaine or heroin use, and exposure to physical violence) and association of the profiles and race/ethnicity with non-use of HAART over time. Methods A hidden Markov model was used to summarize risk factor profiles and changes in profiles over time in a longitudinal sample of HIV-infected women enrolled in the Women's Interagency HIV Study with follow-up from 2002 to 2005 ( n = 802). Results Four risk factor profiles corresponding to four distinct latent states were identified from the five risk factors. Trajectory analysis indicated that states characterized by high probabilities of all risk factors or by low probabilities of all risk factors were both relatively stable over time. Being in the highest risk state did not significantly elevate the odds of HAART non-use (odds ratio [OR], 1.05; 95% confidence interval [CI], 0.6–1.8). However, being in a latent state characterized by elevated probabilities of heavy drinking and exposure to physical violence, along with slight elevations in three other risk factors, significantly increased odds of HAART non-use (OR, 1.4; 95% CI, 1.1–1.9). Conclusion The research suggests that HAART use might be improved by interventions aimed at women who are heavy drinkers with recent exposure to physical violence and evidence of other risk factors. More research about the relationship between clustering and patterns of risk factors and use of HAART is needed.

Panmucositis and chemosensitisation associated with betel quid chewing during dose-dense adjuvant breast cancer chemotherapy

The severity of chemotherapy-induced oral mucositis has previously been reported to be greater in patients who chew betel quid (areca), an addictive habit shared by hundreds of millions of individuals worldwide. Here, we report a case of fulminant panmucositis complicating dose-dense adjuvant breast cancer treatment in a betel-chewing patient without evidence of other risk factors. Grade IV mucositis was triggered by the initial use of standard-dose anthracycline chemotherapy, and involved not only the mouth but also the genital and anal mucosa, as well as other severe non-mucosal toxicities. Despite subsequent treatment with dose-reduced CMF and docetaxel regimens-which are seldom associated with mucosal toxicity at these dose intensities in the absence of neutropenia-high-grade oral mucositis continued to complicate the therapeutic course. These observations suggest that the potentiation of chemotherapy-induced mucositis by quid chewing may not be mediated solely by local effects on the oral epithelium, but also involves the systemic absorption of toxic chemosensitising molecules.

New Generation Antipsychotic Drugs and QTc Interval Prolongation.

BACKGROUND: Recent regulatory and clinical concerns have brought into sharp focus antipsychotic drug-induced QTc interval prolongation, torsades de pointes, and sudden cardiac death. Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns. Because torsades de pointes is rarely found, QTc interval prolongation serves as a surrogate marker for this potentially life-threatening arrhythmia. Current methods of calculating this electrocardiographic parameter have limitations. The primary care physician is a key member of the team managing a patient who requires administration of antipsychotic drugs. This article focuses on new generation antipsychotic drugs and principles useful to both the primary care physician and the psychiatrist. METHOD: PubMed was searched in September 2002 using the terms antipsychotic drug and QT interval. References were examined from review articles describing antipsychotic drugs and the QT interval. The author's files gathered over the past 20 years on the QT interval were also reviewed. RESULTS: Nine cases were available in which drug-induced QTc interval prolongation was associated with new generation antipsychotic drug administration. Eight cases were taken from the literature, and the author added one additional report. The newer agents involved were risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. In one case frequently referenced in the literature, the authors misunderstood their own data showing that QTc interval prolongation did not relate to delayed ventricular repolarization. In another instance, 2 authors reported on the same patient, with important information missing from both articles. No evidence of torsades de pointes appeared in any of the 9 cases. CONCLUSIONS: No evidence is currently available in the literature implicating new generation antipsychotic drugs in the production of torsades de pointes. However, the absence of such evidence does not prove that newer antipsychotic drugs do not cause torsades de pointes. Among patients free of risk factors for QTc interval prolongation and torsades de pointes, current literature does not dictate any specific consultative or laboratory intervention before administering new generation antipsychotic drugs. When risk factors are present, evaluation and intervention specific to those risk factors should dictate the clinician's course of action. More specific guidelines for monitoring the QT interval and risk of torsades de pointes await improved methods of measuring the QTc interval relevant to each patient.

Family risk factors for child and adolescent suicidal behavior.

In this review, the author evaluates the empirical support for the claims that various aspects of family dysfunction are risk factors for completed suicide or suicidal symptoms in childhood or adolescence. There is consistent evidence that a history of physical or sexual abuse is a risk factor and some evidence for other risk factors, including poor family or parent-child communication, loss of caregiver to separation or death, and psychopathology in first-degree relatives. However, the researchers of the vast majority of studies did not attend to whether the putative risk factors preceded the development of suicidal symptoms; thus, most of the claims regarding family risk factors are not justified by their research designs and findings.

Reduced high density lipoproteins as a risk factor after acute myocardial infarction.

In a group of normocholesterolemic, non-diabetic middle-aged males surviving an acute myocardial infarction for 4 +/- 2 years (mean +/- SD), we have previously described a low apolipoprotein A-I and a deficient fibrinolytic activity as two major characteristics. In the present study we have followed morbidity and mortality risk factors for five years in these males. Mortality was 40% in a hypertensive group and 16% in a normotensive group. In the normotensive group mortality was related to reinfarction. Furthermore, patients with a poor prognosis in the normotensive group had lower high density lipoprotein (HDL) cholesterol and lower apolipoprotein A-I concentration in plasma than patients with a good prognosis. Unexpectedly, in the hypertensive group death was related to a low (p less than 0.05) cortisol concentration in urine. It is concluded that a low HDL level may be a bad prognostic sign in males who have sustained an acute myocardial infarction and show no evidence of other risk factors, such as diabetes, hypercholesterolemia or hypertension.