Formulating causal questions and principled statistical answers

Although review papers on causal inference methods are now available, there is a lack of introductory overviews on what they can render and on the guiding criteria for choosing one particular method. This tutorial gives an overview in situations where an exposure of interest is set at a chosen baseline (“point exposure”) and the target outcome arises at a later time point. We first phrase relevant causal questions and make a case for being specific about the possible exposure levels involved and the populations for which the question is relevant. Using the potential outcomes framework, we describe principled definitions of causal effects and of estimation approaches classified according to whether they invoke the no unmeasured confounding assumption (including outcome regression and propensity score-based methods) or an instrumental variable with added assumptions. We mainly focus on continuous outcomes and causal average treatment effects. We discuss interpretation, challenges, and potential pitfalls and illustrate application using a “simulation learner,” that mimics the effect of various breastfeeding interventions on a child's later development. This involves a typical simulation component with generated exposure, covariate, and outcome data inspired by a randomized intervention study. The simulation learner further generates various (linked) exposure types with a set of possible values per observation unit, from which observed as well as potential outcome data are generated. It thus provides true values of several causal effects. R code for data generation and analysis is available on www.ofcaus.org , where SAS and Stata code for analysis is also provided.     

The anti-nausea effects of CB1 agonists are mediated by an action at the visceral insular cortex

BACKGROUND AND PURPOSE

Conditioned gaping reactions reflect nausea-induced behaviour in rats. Cannabinoid 1 receptor (CB₁) agonists interfere with the establishment of nausea-induced conditioned gaping; however, it is not known if their effects are mediated by an action at peripheral or central CB₁ receptors.

EXPERIMENTAL APPROACH

We utilized the conditioned gaping model of nausea to evaluate the effect of peripheral and central administration of the peripherally restricted CB₁ agonist, CB13, on the establishment of LiCl-induced gaping in rats. We further evaluated the ability of HU-210 administered to the gustatory insular cortex (GIC) or visceral insular cortex (VIC) to interfere with LiCl-induced conditioned gaping and determined if this effect was mediated by CB₁ receptors.

KEY RESULTS

Central, but not peripheral, CB13 suppressed LiCl-induced conditioned gaping. Central administration of the potent CB₁ agonist, HU-210, delivered to the VIC, but not the GIC, suppressed the establishment of LiCl-induced gaping reactions, but not LiCl-induced suppression of hedonic reactions or conditioned taste avoidance. This pattern of results suggests that HU-210 delivered to the VIC prevented LiCl-induced nausea, but not learning per se. The suppression of LiCl-induced conditioned gaping by HU-210 was mediated by CB₁ receptors because it was prevented by co-administration of CB₁ antagonist/inverse agonist, AM-251, into the VIC. A high dose of AM-251 (20 µg) administered alone into the VIC did not produce conditioned gaping reactions.

CONCLUSIONS AND IMPLICATIONS

The nausea-relieving effects of CB₁ agonists, but not the nausea-inducing effects of CB₁ inverse agonists, are mediated, at least in part, by their action at the VIC in rats.     

Bacteremia during double-contrast barium enema examination

Forty-five patients undergoing double-contrast barium enema examinations were studied to identify the incidence of transient bacteremia associated with the examination. Blood cultures were obtained immediately prior to the examination and at 5, 10, and 20 minutes after the start of the examination. Blood samples were cultured in both aerobic and anaerobic media, and four of these cultures were positive for organisms that are common skin contaminants. No bacteremia was identified from enteric pathogens. The data herein suggest that patients with cardiac valvular disease are not at greater risk of bacteremia during double-contrast barium enema examinations.     

Radiological assessment of dysphagia with endoscopic correlation

Four hundred fifty consecutive patients with dysphagia were evaluated radiologically over a 14-month period; 127 of these (28.2%) were also examined endoscopically. The most common abnormality seen was dysmotility (34%), followed by hiatal hernia, benign stricture, and esophagitis. Correlation with endoscopy was generally good. Radiologic study demonstrated all cases of esophageal malignancy; radiologic/endoscopic correlation was also strong in patients with moderate or severe esophagitis, though the radiologist had some difficulty detecting mild inflammation. Endoscopy failed to demonstrate some benign strictures. Radiologic study was relatively accurate in detecting significant organic disease; most motility disorders were not detected by endoscopy. For these reasons, as well as lower cost, increased convenience, and patient comfort, radiologic assessment is recommended as the primary method of evaluating patients with dysphagia.     

口服Carvedilol治疗心力衰竭多中心研究(MOCHA)

标题　Ｃａｒｖｅｄｉｌｏｌ对慢性心力衰竭患者左心室功能的改善和存活的提高呈剂量相关性作者　ＢｒｉｓｔｏｗＭＲ，ＧｉｌｂｅｒｔＥＭ，ＡｂｒａｈａｍＷＴ，等　　Ｃｉｒｃｕｌａｔｉｏｎ１９９６，９４：２８０７～２８１６　　研究疾病：充血性心力衰竭。目的：对Ｃａｒｖｅｄｉｌｏｌ治疗慢性心力衰竭患者剂量－疗效特征进行评价。　　设计：随机、双盲、安慰剂对照的多中心研究，剂量效应关系研究。病人资料：共３４５名心力衰竭患者，年龄１８～８５岁，左室射血分数≤０－３５，心力衰竭症状时间≥３月，研究前所有患者必须用利…     

Patient expectations of radiology in noninteractive encounters

Open-ended interviews with 107 patients documented specific patient expectations of radiologic procedures during which there was no direct radiologist-patient interaction. Patient expectations could be classified into those related to the facility and those related to interactions with radiology staff. Among facility-related expectations, waiting time far outweighed all other concerns. Interpersonal skills were the predominant expectation of radiology staff. The role of the radiologist in fulfilling patient expectations was less clear. Only 10% of unprompted patients cited the radiologist as a factor in their expectations. When patients were specifically prompted to discuss the radiologist's role, communication skills, accuracy of interpretation, and interpersonal skills were the predominant concerns.     

Pulmonary embolism after hip or knee replacement: postoperative changes on pulmonary scintigrams in asymptomatic patients

Serial pulmonary imaging has proved to be effective in the evaluation of patients undergoing total joint arthroplasty. A clinical dilemma arises in asymptomatic patients whose postoperative pulmonary images differ from the preoperative images. The authors prospectively evaluated 403 patients with serial imaging to determine the significance of changed postoperative images in asymptomatic patients undergoing total hip or knee arthroplasty. Twenty-two (5.5%) patients had significant changes on postoperative images. Seventeen were asymptomatic; all but one underwent pulmonary angiography. Documented pulmonary emboli were demonstrated in 100% of patients whose postoperative images changed to indicate a high probability of pulmonary embolism, 71% whose images changed to a moderate probability, and 0% whose images changed to indeterminate probability. Overall, pulmonary emboli occurred in 76% of all asymptomatic patients with significantly change postoperative images. Asymptomatic pulmonary embolism is a significant occurrence after total hip or knee repair, and a changed lung scan with appropriate clinical evaluation is an accurate indicator of pulmonary emboli in asymptomatic postarthroplasty patients.     

Anti-Sc1 in pregnancy

Anti-Sc1 was detected in a gravida-2 patient at 12 weeks' gestation. At 29 weeks, the antibody was found to be of the IgG3 subclass with a titer of 16, score 36, by the indirect antiglobulin test, and it produced 7 percent lysis by antibody-dependent cellular cytotoxicity (ADCC) assay, a finding that suggested an unaffected fetus. The titer remained constant throughout the pregnancy, as did the IgG subclass and activity in the ADCC assay. At delivery of the full-term infant, the cord hemoglobin was 13.5 g per dL and the direct antiglobulin test was positive (3+) with anti-IgG. The infant did not require transfusion. A sample taken 9 weeks after delivery showed 44 percent lysis in the ADCC assay. The anti-Sc1 titer was 32, score 65.