Causation in evidence based medicine

Randomized controlled trials (RCTs) have long been recognized as the gold standard for establishing causal relationships in clinical research. Despite that, various limitations of RCTs prevent its widespread implementation, ranging from the ethicality of withholding potentially-lifesaving treatment from a group to relatively poor external validity due to stringent inclusion criteria, amongst others. However, with the introduction of propensity score matching (PSM) as a retrospective statistical tool, new frontiers in establishing causation in clinical research were opened up...

PURPOSE: RNA interference (RNAi)-based therapies that target specific gene products have impacted clinical medicine with 16 FDA approved drugs. RNAi therapy focused on reducing plasma lipoprotein(a) [Lp(a)] levels are under evaluation. FINDINGS: RNAi-based therapies have made significant progress over the past 2 decades and currently consist of antisense oligonucleotides (ASO) and small interfering RNA (siRNA). Chemical modification of the RNA backbone and conjugation of siRNA enables efficient gene silencing in hepatocytes allowing development of effective cholesterol lowering therapies...

Multiple Sclerosis (MS) is an immune-related disease and the relationship between MS and cancer has raised attention. Previous studies of the relationship between MS and cancer have reached conflicting conclusions. In this study, the two-sample MR method is used to investigate whether MS has a causal correlation with cancers and offer scientific evidence for cancer prevention. Single nucleotide polymorphisms (SNPs) related to MS were obtained from the genome-wide association study (GWAS) based on International Multiple Sclerosis Genetics Consortium (IMSGC) and SNPs related to 15 types of cancers were obtained from the GWASs based on UK Biobank...

Beef × dairy crossbred cattle (n=615) were used to evaluate the effect of pre-harvest indicator traits and genotypes on accuracy of estimated breeding values (EBV) of seedstock candidates for selection. Genotypes for 100,000 single nucleotide polymorphisms (SNP) were provided by the American Simmental Association of purebred and crossbred seedstock animals (n=2,632). Five hundred ninety-five of the 615 beef x dairy cattle had carcass camera and ultrasound data. Phenotypes were not used for any of the seedstock animals even though some may have had performance and ultrasound data...

BACKGROUND: Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits. METHODS: The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480)...

OBJECTIVES: Nonalcoholic fatty liver disease is one of the emerging liver diseases affecting 20%-30% of the population creating a burden on public health worldwide and has been associated with the causation of multiple diseases. Besides exercise, several drugs are being used in patients based on clinical evidence especially vitamin E, a potent antioxidant to reduce the oxidative stress responsible for the development and progression of nonalcoholic fatty liver disease. This study aims at evaluating the effect of exercise and pharmacotherapy on nonalcoholic fatty liver disease...

OBJECTIVE: to assess the causal role of the relationship between loading and the onset of non-specific low back pain (NSLBP) and persistence of NSLBP (CLBP). DESIGN: Scoping review. LITERATURE SEARCH: We searched the literature from 2010 until May 2021 using a combination of terms related to (spinal) load and the Bradford-Hill (BH) criteria. STUDY SELECTION CRITERIA: Operational definitions were developed for every criterion of the BH framework for causality. Study selection was based on the causal role of load in the onset of NSLBP and persistence of CLBP...

BACKGROUND: Most government efforts to control the COVID-19 pandemic revolved around non-pharmaceutical interventions (NPIs) and vaccination. However, many respiratory diseases show distinctive seasonal trends. In this manuscript, we examined the contribution of these three factors to the progression of the COVID-19 pandemic. METHODS: Pearson correlation coefficients and time-lagged analysis were used to examine the relationship between NPIs, vaccinations and seasonality (using the average incidence of endemic human beta-coronaviruses in Sweden over a 10-year period as a proxy) and the progression of the COVID-19 pandemic as tracked by deaths; cases; hospitalisations; intensive care unit occupancy and testing positivity rates in six Northern European countries (population 99...

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating, and multi-faceted illness. Heterogenous onset and clinical presentation with additional comorbidities make it difficult to diagnose, characterize, and successfully treat. Current treatment guidelines focus on symptom management, but with no clear target or causative mechanism, remission rates are low, and fewer than 5% of patients return to their pre-morbid activity levels. Therefore, there is an urgent need to undertake robust clinical trials to identify effective treatments...

In 2017, highly fatal canine leptospirosis emerged in Sydney, Australia. Based on results of microscopic agglutination testing (MAT), serovar Copenhageni appeared to be the most common causative serovar. Prior to this, no clinical cases had been reported since 1976. In a serosurvey of healthy dogs in Australian shelters in 2004, 2.4% of 431 New South Wales dogs had serological evidence of exposure to Copenhageni, the most prevalent serovar. The aim of this study was to estimate the current prevalence of Leptospira exposure and associated serovars in healthy Sydney dogs, previously unvaccinated against Leptospira...

Background There has been a marked increase in the global prevalence of obesity over recent decades with an estimated 1.9 billion adults who are overweight or living with obesity. This is associated with a sharp rise in the prevalence of cardiorenal metabolic diseases such as type 2 diabetes mellitus, chronic kidney disease, and heart failure. Given recent evidence of the efficacy of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists on cardiorenal protection and weight reduction, it is reasonable to investigate common causative pathways for cardiorenal metabolic diseases...

AIMS: This protocol describes a forthcoming systematic review of the question: 'What are the long-term effects of historical influenza pandemics on mental health, resulting either from illness itself or the social or economic effects of pandemics and public health responses?' METHODS: We will review studies that investigate associations between influenza pandemics and long-term mental-health impacts. Following the PICO framework, populations (P) may include those with and without pre-existing mental-health symptoms or conditions...

Purpose  This report is intended to analyze the root causes for the current gap between the nursing workforce and population needs in the United States. It aims to consolidate what is known about these contributing reasons and provide evidence-based recommendations for action. Methods  The report utilized the Sample, Phenomenon of Interest, Design, Evaluation, Research type framework to develop the research question and the 5 Whys methodology for the root cause analysis. Results  This report highlighted six major causative problems, including workforce market mismatch, poor financing design, inadequate governance, flawed technologies, insufficient research, and suboptimal service delivery...

The objective of anti-aging medicine is to decelerate the aging process and mitigate its associated effects, such as susceptibility to cancer, diabetes, and cardiovascular and neurodegenerative diseases. This review provides an overview of the latest advancements in this field, considering both pharmaceutical and non-pharmaceutical approaches. Electronic literature search involved three databases: MEDLINE, Cochrane, and Google Scholar, supplemented by other available literature. Strategies for delaying aging and related diseases comprise pharmaceutical interventions and lifestyle choices...

BACKGROUND: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship. METHODS: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants...

PURPOSE: The relationship between diabetes mellitus and keratoconus remains controversial. This study aimed to assess the potential causal relationships among type 2 diabetes, glycemic traits, and the risk of keratoconus. METHODS: We used a two-sample Mendelian randomization (MR) design based on genome-wide association summary statistics. Fasting glucose, proinsulin levels, adiponectin, hemoglobin A1c (HbA1c) and type 2 diabetes with and without body mass index (BMI) adjustment were used as exposures and keratoconus was used as the outcome...

Fibrinogen and homocysteine (HCY) are molecules known to play a role in vascular homeostasis, and their blood levels are often elevated in patients with metabolic syndrome. Recent evidence suggests that sudden sensorineural hearing loss (SSHL) may have a vascular origin. This has led many authors to advocate that fibrinogen, homocysteine, and metabolic syndrome (MetS) may play a direct role in SSHL. The aim of this brief review is to examine the role and influence of these molecules and MetS on the mechanisms of SSHL...

Occupational medical research involves the collection and analysis of data to draw conclusions about the causes and prevention of workplace injuries and diseases. However, there has been criticism that some studies lack rigour in determining causation. This article examines the similarities and differences between occupational medical research and particle physics in terms of their approach to hypothesis testing, statistical methods, and confounder control. The article also explores the use of criteria such as the Bradford Hill criteria to determine causation in occupational medical research...

BACKGROUND: Chronic kidney disease (CKD) is a significant risk factor for cardiovascular disease (CVD) and death. Increased oxidative stress in people with CKD has been implicated as a potential causative factor. Antioxidant therapy decreases oxidative stress and may consequently reduce cardiovascular morbidity and death in people with CKD. This is an update of a Cochrane review first published in 2012. OBJECTIVES: To examine the benefits and harms of antioxidant therapy on death and cardiovascular and kidney endpoints in adults with CKD stages 3 to 5, patients undergoing dialysis, and kidney transplant recipients...

IMPORTANCE: Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested. OBJECTIVE: To examine the association between adult ADHD and the risk of dementia. DESIGN, SETTING, AND PARTICIPANTS: This prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020...