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JAMA Network Open Jan 2023Despite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the...
IMPORTANCE
Despite discrete etiologies leading to delirium, it is treated as a common end point in hospital and in clinical trials, and delirium research may be hampered by the attempt to treat all instances of delirium similarly, leaving delirium management as an unmet need. An individualized approach based on unique patterns of delirium pathophysiology, as reflected in predisposing factors and precipitants, may be necessary, but there exists no accepted method of grouping delirium into distinct etiologic subgroups.
OBJECTIVE
To conduct a systematic review to identify potential predisposing and precipitating factors associated with delirium in adult patients agnostic to setting.
EVIDENCE REVIEW
A literature search was performed of PubMed, Embase, Web of Science, and PsycINFO from database inception to December 2021 using search Medical Subject Headings (MeSH) terms consciousness disorders, confusion, causality, and disease susceptibility, with constraints of cohort or case-control studies. Two reviewers selected studies that met the following criteria for inclusion: published in English, prospective cohort or case-control study, at least 50 participants, delirium assessment in person by a physician or trained research personnel using a reference standard, and results including a multivariable model to identify independent factors associated with delirium.
FINDINGS
A total of 315 studies were included with a mean (SD) Newcastle-Ottawa Scale score of 8.3 (0.8) out of 9. Across 101 144 patients (50 006 [50.0%] male and 49 766 [49.1%] female patients) represented (24 015 with delirium), studies reported 33 predisposing and 112 precipitating factors associated with delirium. There was a diversity of factors associated with delirium, with substantial physiological heterogeneity.
CONCLUSIONS AND RELEVANCE
In this systematic review, a comprehensive list of potential predisposing and precipitating factors associated with delirium was found across all clinical settings. These findings may be used to inform more precise study of delirium's heterogeneous pathophysiology and treatment.
Topics: Adult; Humans; Male; Female; Disease Susceptibility; Delirium; Precipitating Factors; Prospective Studies; Case-Control Studies
PubMed: 36607634
DOI: 10.1001/jamanetworkopen.2022.49950 -
Current Protocols Dec 2021Mendelian randomization is a framework that uses measured variation in genes for assessing and estimating the causal effect of an exposure on an outcome. Multivariable...
Mendelian randomization is a framework that uses measured variation in genes for assessing and estimating the causal effect of an exposure on an outcome. Multivariable Mendelian randomization is an extension that can assess the causal effect of multiple exposures on an outcome, and can be advantageous when considering a set (>1) of potentially correlated candidate risk factors in evaluating the causal effect of each on a health outcome, accounting for measured pleiotropy. This can be seen, for example, in determining the causal effects of lipids and cholesterol on type 2 diabetes risk, where the correlated risk factors share genetic predictors. Similar to univariate Mendelian randomization, multivariable Mendelian randomization can be conducted using two-sample summary-level data where the gene-exposure and gene-outcome associations are derived from separate samples from the same underlying population. Here, we present a protocol for conducting a two-sample multivariable Mendelian randomization study using the 'MVMR' package in R and summary-level genetic data. We also provide a protocol for searching and obtaining instruments using available data sources in the 'MRInstruments' R package. Finally, we provide general guidelines and discuss the utility of performing a multivariable Mendelian randomization analysis for simultaneously assessing causality of multiple exposures. © 2021 Wiley Periodicals LLC. Basic Protocol: Performing a two-sample multivariable Mendelian randomization analysis using the 'MVMR' package in R and summarized genetic data Support Protocol 1: Installing the 'MVMR' R package Support Protocol 2: Obtaining instruments from the 'MRInstruments' R package.
Topics: Causality; Diabetes Mellitus, Type 2; Genetic Variation; Humans; Mendelian Randomization Analysis; Risk Factors
PubMed: 34936225
DOI: 10.1002/cpz1.335 -
European Heart Journal May 2023Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and...
AIMS
Perioperative myocardial infarction/injury (PMI) following non-cardiac surgery is a frequent cardiac complication. Better understanding of the underlying aetiologies and outcomes is urgently needed.
METHODS AND RESULTS
Aetiologies of PMIs detected within an active surveillance and response programme were centrally adjudicated by two independent physicians based on all information obtained during clinically indicated PMI work-up including cardiac imaging among consecutive high-risk patients undergoing major non-cardiac surgery in a prospective multicentre study. PMI aetiologies were hierarchically classified into 'extra-cardiac' if caused by a primarily extra-cardiac disease such as severe sepsis or pulmonary embolism; and 'cardiac', further subtyped into type 1 myocardial infarction (T1MI), tachyarrhythmia, acute heart failure (AHF), or likely type 2 myocardial infarction (lT2MI). Major adverse cardiac events (MACEs) including acute myocardial infarction, AHF (both only from day 3 to avoid inclusion bias), life-threatening arrhythmia, and cardiovascular death as well as all-cause death were assessed during 1-year follow-up. Among 7754 patients (age 45-98 years, 45% women), PMI occurred in 1016 (13.1%). At least one MACE occurred in 684/7754 patients (8.8%) and 818/7754 patients died (10.5%) within 1 year. Outcomes differed starkly according to aetiology: in patients with extra-cardiac PMI, T1MI, tachyarrhythmia, AHF, and lT2MI 51%, 41%, 57%, 64%, and 25% had MACE, and 38%, 27%, 40%, 49%, and 17% patients died within 1 year, respectively, compared to 7% and 9% in patients without PMI. These associations persisted in multivariable analysis.
CONCLUSION
At 1 year, most PMI aetiologies have unacceptably high rates of MACE and all-cause death, highlighting the urgent need for more intensive treatments.
STUDY REGISTRATION
https://clinicaltrials.gov/ct2/show/NCT02573532.
Topics: Humans; Female; Middle Aged; Aged; Aged, 80 and over; Male; Prospective Studies; Risk Factors; Biomarkers; Myocardial Infarction; Heart Diseases
PubMed: 36705050
DOI: 10.1093/eurheartj/ehac798 -
Cold Spring Harbor Perspectives in... Jan 2022Mendelian randomization (MR) is a method of studying the causal effects of modifiable exposures (i.e., potential risk factors) on health, social, and economic outcomes... (Review)
Review
Mendelian randomization (MR) is a method of studying the causal effects of modifiable exposures (i.e., potential risk factors) on health, social, and economic outcomes using genetic variants associated with the specific exposures of interest. MR provides a more robust understanding of the influence of these exposures on outcomes because germline genetic variants are randomly inherited from parents to offspring and, as a result, should not be related to potential confounding factors that influence exposure-outcome associations. The genetic variant can therefore be used as a tool to link the proposed risk factor and outcome, and to estimate this effect with less confounding and bias than conventional epidemiological approaches. We describe the scope of MR, highlighting the range of applications being made possible as genetic data sets and resources become larger and more freely available. We outline the MR approach in detail, covering concepts, assumptions, and estimation methods. We cover some common misconceptions, provide strategies for overcoming violation of assumptions, and discuss future prospects for extending the clinical applicability, methodological innovations, robustness, and generalizability of MR findings.
Topics: Causality; Mendelian Randomization Analysis; Risk Factors
PubMed: 34426474
DOI: 10.1101/cshperspect.a040501 -
European Journal of Heart Failure May 2015The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality. (Observational Study)
Observational Study
AIMS
The aim of this study was to investigate the clinical picture and outcome of cardiogenic shock and to develop a risk prediction score for short-term mortality.
METHODS AND RESULTS
The CardShock study was a multicentre, prospective, observational study conducted between 2010 and 2012. Patients with either acute coronary syndrome (ACS) or non-ACS aetiologies were enrolled within 6 h from detection of cardiogenic shock defined as severe hypotension with clinical signs of hypoperfusion and/or serum lactate >2 mmol/L despite fluid resuscitation (n = 219, mean age 67, 74% men). Data on clinical presentation, management, and biochemical variables were compared between different aetiologies of shock. Systolic blood pressure was on average 78 mmHg (standard deviation 14 mmHg) and mean arterial pressure 57 (11) mmHg. The most common cause (81%) was ACS (68% ST-elevation myocardial infarction and 8% mechanical complications); 94% underwent coronary angiography, of which 89% PCI. Main non-ACS aetiologies were severe chronic heart failure and valvular causes. In-hospital mortality was 37% (n = 80). ACS aetiology, age, previous myocardial infarction, prior coronary artery bypass, confusion, low LVEF, and blood lactate levels were independently associated with increased mortality. The CardShock risk Score including these variables and estimated glomerular filtration rate predicted in-hospital mortality well (area under the curve 0.85).
CONCLUSION
Although most commonly due to ACS, other causes account for one-fifth of cases with shock. ACS is independently associated with in-hospital mortality. The CardShock risk Score, consisting of seven common variables, easily stratifies risk of short-term mortality. It might facilitate early decision-making in intensive care or guide patient selection in clinical trials.
TRIAL REGISTRATION
NCT01374867.
Topics: Acute Coronary Syndrome; Aged; Coronary Angiography; Female; Heart Failure; Heart Valve Diseases; Humans; Male; Middle Aged; Prospective Studies; Risk Factors; Shock, Cardiogenic
PubMed: 25820680
DOI: 10.1002/ejhf.260 -
Cancer Causes & Control : CCC Oct 2014Research involving the discovery of novel anticancer drugs and treatments hold precedence among the general public. However, investigating the etiology and epidemiology...
BACKGROUND
Research involving the discovery of novel anticancer drugs and treatments hold precedence among the general public. However, investigating the etiology and epidemiology of malignancies can have a significant effect on reducing the prevalence of cancer in society. Understanding risk factors that drive neoplastic development can provide educated individuals the opportunity to avoid such catalysts.
METHODS
Literature searches were conducted on prominent magazine and newspaper sources to analyze the accuracy and relevance the material had toward cancer prevention. Additionally, two professionals involved in oncology were interviewed to gain a more personal view of the population's knowledge on cancer awareness and prevention.
RESULTS
The lack of attention paid to the understanding of cancer and its subsequent prevention has resulted in fundamental misconceptions that facilitate the development of neoplastic growths.
CONCLUSIONS
Addressing the lack of attention paid to cancer awareness and prevention through proper education can have a significant effect on limiting the impact cancer has on society.
Topics: Adult; Causality; Health Knowledge, Attitudes, Practice; Humans; Neoplasms; Prevalence; Public Opinion; Risk Factors
PubMed: 25011402
DOI: 10.1007/s10552-014-0428-9 -
Human Reproduction Update Sep 2023Endometriosis remains a poorly understood disease, despite its high prevalence and debilitating symptoms. The overlap in symptoms and the increased risk of multiple... (Review)
Review
BACKGROUND
Endometriosis remains a poorly understood disease, despite its high prevalence and debilitating symptoms. The overlap in symptoms and the increased risk of multiple other traits in women with endometriosis is becoming increasingly apparent through epidemiological data. Genetic studies offer a method of investigating these comorbid relationships through the assessment of causal relationships with Mendelian randomization (MR), as well as identification of shared genetic variants and genes involved across traits. This has the capacity to identify risk factors for endometriosis as well as provide insight into the aetiology of disease.
OBJECTIVE AND RATIONALE
We aim to review the current literature assessing the relationship between endometriosis and other traits using genomic data, primarily through the methods of MR and genetic correlation. We critically examine the limitations of these studies in accordance with the assumptions of the utilized methods.
SEARCH METHODS
The PubMed database was used to search for peer-reviewed original research articles using the terms 'Mendelian randomization endometriosis' and '"genetic correlation" endometriosis'. Additionally, a Google Scholar search using the terms '"endometriosis" "mendelian randomization" "genetic correlation"' was performed. All relevant publications (n = 21) published up until 7 October 2022 were included in this review. Upon compilation of all traits with published MR and/or genetic correlation with endometriosis, additional epidemiological and genetic information on their comorbidity with endometriosis was sourced by searching for the trait in conjunction with 'endometriosis' on Google Scholar.
OUTCOMES
The association between endometriosis and multiple pain, gynaecological, cancer, inflammatory, gastrointestinal, psychological, and anthropometric traits has been assessed using MR analysis and genetic correlation analysis. Genetic correlation analyses provide evidence that genetic factors contributing to endometriosis are shared with multiple traits: migraine, uterine fibroids, subtypes of ovarian cancer, melanoma, asthma, gastro-oesophageal reflux disease, gastritis/duodenitis, and depression, suggesting the involvement of multiple biological mechanisms in endometriosis. The assessment of causality with MR has revealed several potential causes (e.g. depression) and outcomes (e.g. ovarian cancer and uterine fibroids) of a genetic predisposition to endometriosis; however, interpretation of these results requires consideration of potential violations of the MR assumptions.
WIDER IMPLICATIONS
Genomic studies have demonstrated that there is a molecular basis for the co-occurrence of endometriosis with other traits. Dissection of this overlap has identified shared genes and pathways, which provide insight into the biology of endometriosis. Thoughtful MR studies are necessary to ascertain causality of the comorbidities of endometriosis. Given the significant diagnostic delay of endometriosis of 7-11 years, determining risk factors is necessary to aid diagnosis and reduce the disease burden. Identification of traits for which endometriosis is a risk factor is important for holistic treatment and counselling of the patient. The use of genomic data to disentangle the overlap of endometriosis with other traits has provided insights into the aetiology of endometriosis.
Topics: Mendelian Randomization Analysis; Endometriosis; Comorbidity; Humans; Female; Risk Factors
PubMed: 37159502
DOI: 10.1093/humupd/dmad009 -
Diabetologia May 2023Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the... (Review)
Review
Diabetes and its complications cause a heavy disease burden globally. Identifying exposures, risk factors and molecular processes causally associated with the development of diabetes can provide important evidence bases for disease prevention and spur novel therapeutic strategies. Mendelian randomisation (MR), an epidemiological approach that uses genetic instruments to infer causal associations between an exposure and an outcome, can be leveraged to complement evidence from observational and clinical studies. This narrative review aims to summarise the evidence on potential causal risk factors for diabetes by integrating published MR studies on type 1 and 2 diabetes, and to reflect on future perspectives of MR studies on diabetes. Despite the genetic influence on type 1 diabetes, few MR studies have been conducted to identify causal exposures or molecular processes leading to increased disease risk. In type 2 diabetes, MR analyses support causal associations of somatic, mental and lifestyle factors with development of the disease. These studies have also identified biomarkers, some of them derived from the gut microbiota, and molecular processes leading to increased disease risk. These studies provide valuable data to better understand disease pathophysiology and explore potential therapeutic targets. Because genetic association studies have mostly been restricted to participants of European descent, multi-ancestry cohorts are needed to examine the role of different types of physical activity, dietary components, metabolites, protein biomarkers and gut microbiome in diabetes development.
Topics: Humans; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Risk Factors; Causality; Disease Susceptibility; Mendelian Randomization Analysis; Genome-Wide Association Study
PubMed: 36786839
DOI: 10.1007/s00125-023-05879-7 -
The Lancet. Infectious Diseases Sep 2017The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides an up-to-date analysis of the burden of diarrhoeal diseases. This study assesses...
Estimates of global, regional, and national morbidity, mortality, and aetiologies of diarrhoeal diseases: a systematic analysis for the Global Burden of Disease Study 2015.
BACKGROUND
The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) provides an up-to-date analysis of the burden of diarrhoeal diseases. This study assesses cases, deaths, and aetiologies spanning the past 25 years and informs the changing picture of diarrhoeal disease worldwide.
METHODS
We estimated diarrhoeal mortality by age, sex, geography, and year using the Cause of Death Ensemble Model (CODEm), a modelling platform shared across most causes of death in the GBD 2015 study. We modelled diarrhoeal morbidity, including incidence and prevalence, using a meta-regression platform called DisMod-MR. We estimated aetiologies for diarrhoeal diseases using a counterfactual approach that incorporates the aetiology-specific risk of diarrhoeal disease and the prevalence of the aetiology in diarrhoea episodes. We used the Socio-demographic Index, a summary indicator derived from measures of income per capita, educational attainment, and fertility, to assess trends in diarrhoeal mortality. The two leading risk factors for diarrhoea-childhood malnutrition and unsafe water, sanitation, and hygiene-were used in a decomposition analysis to establish the relative contribution of changes in diarrhoea disability-adjusted life-years (DALYs).
FINDINGS
Globally, in 2015, we estimate that diarrhoea was a leading cause of death among all ages (1·31 million deaths, 95% uncertainty interval [95% UI] 1·23 million to 1·39 million), as well as a leading cause of DALYs because of its disproportionate impact on young children (71·59 million DALYs, 66·44 million to 77·21 million). Diarrhoea was a common cause of death among children under 5 years old (499 000 deaths, 95% UI 447 000-558 000). The number of deaths due to diarrhoea decreased by an estimated 20·8% (95% UI 15·4-26·1) from 2005 to 2015. Rotavirus was the leading cause of diarrhoea deaths (199 000, 95% UI 165 000-241 000), followed by Shigella spp (164 300, 85 000-278 700) and Salmonella spp (90 300, 95% UI 34 100-183 100). Among children under 5 years old, the three aetiologies responsible for the most deaths were rotavirus, Cryptosporidium spp, and Shigella spp. Improvements in safe water and sanitation have decreased diarrhoeal DALYs by 13·4%, and reductions in childhood undernutrition have decreased diarrhoeal DALYs by 10·0% between 2005 and 2015.
INTERPRETATION
At the global level, deaths due to diarrhoeal diseases have decreased substantially in the past 25 years, although progress has been faster in some countries than others. Diarrhoea remains a largely preventable disease and cause of death, and continued efforts to improve access to safe water, sanitation, and childhood nutrition will be important in reducing the global burden of diarrhoea.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Adolescent; Adult; Aged; Child; Child Nutrition Disorders; Child, Preschool; Diarrhea; Global Burden of Disease; Global Health; Humans; Incidence; Infant; Life Expectancy; Middle Aged; Mortality; Prevalence; Quality-Adjusted Life Years; Risk Factors; Sanitation
PubMed: 28579426
DOI: 10.1016/S1473-3099(17)30276-1 -
British Journal of Sports Medicine Nov 2019Achilles tendinopathy is a common problem, but its exact aetiology remains unclear.
BACKGROUND
Achilles tendinopathy is a common problem, but its exact aetiology remains unclear.
OBJECTIVE
To evaluate the association between potential clinical risk factors and Achilles tendinopathy.
DESIGN
Systematic review.
DATA SOURCES
The databases Embase, MEDLINE Ovid, Web of Science, Cochrane Library and Google Scholar were searched up to February 2018.
ELIGIBILITY CRITERIA
To answer our research question, cohort studies investigating risk factors for Achilles tendinopathy in humans were included. We restricted our search to potential clinical risk factors (imaging studies were excluded).
RESULTS
We included 10 cohort studies, all with a high risk of bias, from 5111 publications identified. There is limited evidence for nine risk factors: (1) prior lower limb tendinopathy or fracture, (2) use of ofloxacin (quinolone) antibiotics, (3) an increased time between heart transplantation and initiation of quinolone treatment for infectious disease, (4) moderate alcohol use, (5) training during cold weather, (6) decreased isokinetic plantar flexor strength, (7) abnormal gait pattern with decreased forward progression of propulsion, (8) more lateral foot roll-over at the forefoot flat phase and (9) creatinine clearance of <60 mL/min in heart transplant patients. Twenty-six other putative risk factors were not associated with Achilles tendinopathy, including being overweight, static foot posture and physical activity level.
CONCLUSION
From an ocean of studies with high levels of bias, we extracted nine clinical risk factors that may increase a person's risk of Achilles tendinopathy. Clinicians may consider ofloxacin use, alcohol consumption and a reduced plantar flexor strength as modifiable risk factors when treating patients with Achilles tendinopathy.
TRIAL REGISTRATION NUMBER
CRD42017053258.
Topics: Achilles Tendon; Alcohol Drinking; Cold Temperature; Foot; Gait; Heart Transplantation; Humans; Ofloxacin; Posture; Risk Factors; Tendinopathy
PubMed: 30718234
DOI: 10.1136/bjsports-2018-099991