We compared the clinical characteristics and outcomes of young patients with myocardial infarction with nonobstructive coronary arteries (MINOCA) versus obstructive disease (myocardial infarction due ...to coronary artery disease MI-CAD) and among patients with MINOCA by sex and subtype.
Between 2008 and 2012, VIRGO (Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients) prospectively enrolled acute myocardial infarction patients aged 18 to 55 years in 103 hospitals at a 2:1 ratio of women to men. Using an angiographically driven taxonomy, we defined patients as having MI-CAD if there was revascularization or plaque ≥50% and as having MINOCA if there was <50% obstruction or a nonplaque mechanism. Patients who did not have an angiogram or who received thrombolytics before an angiogram were excluded. Outcomes included 1- and 12-month mortality and functional (Seattle Angina Questionnaire SAQ) and psychosocial status. Of 2690 patients undergoing angiography, 2374 (88.4%) had MI-CAD, 299 (11.1%) had MINOCA, and 17 (0.6%) remained unclassified. Women had 5 times higher odds of having MINOCA than men (14.9% versus 3.5%; odds ratio: 4.84; 95% confidence interval, 3.29-7.13). MINOCA patients were more likely to be without traditional cardiac risk factors (8.7% versus 1.3%;
<0.001) but more predisposed to hypercoaguable states than MI-CAD patients (3.0% versus 1.3%;
=0.036). Women with MI-CAD were more likely than those with MINOCA to be menopausal (55.2% versus 41.2%;
<0.001) or to have a history of gestational diabetes mellitus (16.8% versus 11.0%;
=0.028). The MINOCA mechanisms varied: a nonplaque mechanism was identified for 75 patients (25.1%), and their clinical profiles and management also varied. One- and 12-month mortality with MINOCA and MI-CAD was similar (1-month: 1.1% and 1.7%
=0.43; 12-month: 0.6% and 2.3%
=0.68, respectively), as was adjusted 12-month SAQ quality of life (76.5 versus 73.5, respectively;
=0.06).
Young patients with MINOCA were more likely women, had a heterogeneous mechanistic profile, and had clinical outcomes that were comparable to those of MI-CAD patients.
URL: http://www.clinicaltrials.gov. Unique identifier: NCT00597922.
Randomized clinical trials are the gold standard for evaluating interventions as randomized assignment equalizes known and unknown characteristics between intervention groups. However, when ...participants miss visits, the ability to conduct an intent-to-treat analysis and draw conclusions about a causal link is compromised. As guidance to those performing clinical trials, this review is a non-technical overview of the consequences of missing data and a prescription for its treatment beyond the typical analytic approaches to the entire research process. Examples of bias from incorrect analysis with missing data and discussion of the advantages/disadvantages of analytic methods are given. As no single analysis is definitive when missing data occurs, strategies for its prevention throughout the course of a trial are presented. We aim to convey an appreciation for how missing data influences results and an understanding of the need for careful consideration of missing data during the design, planning, conduct, and analytic stages.
Among patients with spondylolisthesis and lumbar spinal stenosis, laminectomy with fusion was associated with modestly greater improvement in physical health–related quality of life than laminectomy ...alone but not with significantly greater reduction in disability related to back pain.
The increased use of the lumbar spinal fusion procedure in the United States, along with the wide variation in practice, is attracting interest from multiple stakeholders, including patients, physicians, payers, and policymakers. In a report published in 2014, spinal fusion (465,000 hospital-based procedures in 2011) accounted for the highest aggregate hospital costs ($12.8 billion in 2011) of any surgical procedure performed in U.S. hospitals.
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The randomized, controlled Spine Patient Outcomes Research Trial (SPORT) showed that surgery was superior to nonoperative care for the management of lumbar degenerative spondylolisthesis.
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In SPORT, most patients in the surgical group were treated by means . . .
Clinical research in neurodevelopmental disorders remains reliant upon clinician and caregiver measures. Limitations of these approaches indicate a need for objective, quantitative, and reliable ...biomarkers to advance clinical research. Extant research suggests the potential utility of multiple candidate biomarkers; however, effective application of these markers in trials requires additional understanding of replicability, individual differences, and intra-individual stability over time. The Autism Biomarkers Consortium for Clinical Trials (ABC-CT) is a multi-site study designed to investigate a battery of electrophysiological (EEG) and eye-tracking (ET) indices as candidate biomarkers for autism spectrum disorder (ASD). The study complements published biomarker research through: inclusion of large, deeply phenotyped cohorts of children with ASD and typical development; a longitudinal design; a focus on well-evidenced candidate biomarkers harmonized with an independent sample; high levels of clinical, regulatory, technical, and statistical rigor; adoption of a governance structure incorporating diverse expertise in the ASD biomarker discovery and qualification process; prioritization of open science, including creation of a repository containing biomarker, clinical, and genetic data; and use of economical and scalable technologies that are applicable in developmental populations and those with special needs. The ABC-CT approach has yielded encouraging results, with one measure accepted into the FDA's Biomarker Qualification Program to date. Through these advances, the ABC-CT and other biomarker studies in progress hold promise to deliver novel tools to improve clinical trials research in ASD.
Americans of lower SES use tobacco products at disproportionately high rates and are over-represented as patients of emergency departments. Accordingly, emergency department visits are an ideal time ...to initiate tobacco treatment and aftercare for this vulnerable and understudied population. This research estimates the costs per quit of emergency department smoking-cessation interventions and compares them with those of other approaches.
Previously published research described the effectiveness of 2 multicomponent smoking cessation interventions, including brief negotiated interviewing, nicotine replacement therapy, quitline referral, and follow-up communication. Study 1 (collected in 2010–2012) only analyzed the combined interventions. Study 2 (collected in 2017–2019) analyzed the intervention components independently. Costs per participant and per quit were estimated separately, under distinct intervention with dedicated staff and intervention with repurposed staff assumptions. The distinction concerns whether the intervention used dedicated staff for delivery or whether time from existing staff was repurposed for intervention if available.
Data were analyzed in 2021–2022. In the first study, the cost per participant was $860 (2018 dollars), and the cost per quit was $11,814 (95% CI=$7,641, $25,423) (dedicated) and $227 per participant and $3,121 per quit (95% CI=$1,910, $7,012) (repurposed). In Study 2, the combined effect of brief negotiated interviewing, nicotine replacement therapy, and quitline cost $808 per participant and $6,100 per quit (dedicated) (95% CI=$4,043, $12,274) and $221 per participant and $1,669 per quit (95% CI=$1,052, $3,531) (repurposed).
Costs varied considerably per method used but were comparable with those of other smoking cessation interventions.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To examine whether delayed surgical intervention in adult patients with acute appendicitis is safe by correlating the interval from onset of symptoms to operation (total interval) with the degree of ...pathology and incidence of postoperative complications.
Prompt appendectomy has long been the standard of care for acute appendicitis because of the risk of progression to advanced pathology. This time-honored practice has been recently challenged by studies in pediatric patients, which suggested that acute appendicitis can be managed in an elective manner once antibiotic therapy is initiated. No such data are available in adult patients with acute appendicitis.
A retrospective review of 1081 patients who underwent an appendectomy for acute appendicitis between 1998 and 2004 was conducted. The following parameters were monitored and correlated: demographics, time from onset of symptoms to arrival at the emergency room (patient interval) and from arrival to the emergency room to the operating room (hospital interval), physical, computed tomography (CT scan) and pathologic findings, complications, length of stay, and length of antibiotic treatment. Pathologic state was graded 1 (G1) for acute appendicitis, 2 (G2) for gangrenous acute appendicitis, 3 (G3) for perforation or phlegmon, and 4 (G4) for a periappendicular abscess.
The risk of advanced pathology, defined as a higher pathology grade, increased with the total interval. When this interval was <12 hours, the risk of developing G1, G2, G3, and G4, was 94%, 0%, 3%, and 3%, respectively. These values changed to 60%, 7%, 27%, and 6%, respectively, when the total interval was 48 to 71 hours and to 54%, 7%, 26%, and 13% for longer than 71 hours. The odds for progressive pathology was 13 times higher for the total interval >71 hours group compared with total interval<12 hours (95% confidence interval = 4.7-37.1). Although both prolonged patient and hospital intervals were associated with advanced pathology, prehospital delays were more profoundly related to worsening pathology compared with in-hospital delays (P < 0.001). Advanced pathology was associated with tenderness to palpation beyond the right lower quadrant (P < 0.001), guarding (P < 0.001), rebound (P < 0.001), and CT scan findings of peritoneal fluid (P = 0.01), fecalith (P = 0.01), dilation of the appendix (P < 0.001), and perforation (P < 0.001). Increased length of hospital stay (P < 0.001) and antibiotic treatment (P < 0.001) as well as postoperative complications (P < 0.001) also correlated with progressive pathology.
In adult patients with acute appendicitis, the risk of developing advanced pathology and postoperative complications increases with time; therefore, delayed appendectomy is unsafe. As delays in seeking medical help are difficult to control, prompt appendectomy is mandatory. Because these conclusions are derived from retrospective data, a prospective study is required to confirm their validity.
Little is known about the environmental and public health impact of unconventional natural gas extraction activities, including hydraulic fracturing, that occur near residential areas.
Our aim was to ...assess the relationship between household proximity to natural gas wells and reported health symptoms.
We conducted a hypothesis-generating health symptom survey of 492 persons in 180 randomly selected households with ground-fed wells in an area of active natural gas drilling. Gas well proximity for each household was compared with the prevalence and frequency of reported dermal, respiratory, gastrointestinal, cardiovascular, and neurological symptoms.
The number of reported health symptoms per person was higher among residents living < 1 km (mean ± SD, 3.27 ± 3.72) compared with > 2 km from the nearest gas well (mean ± SD, 1.60 ± 2.14; p = 0.0002). In a model that adjusted for age, sex, household education, smoking, awareness of environmental risk, work type, and animals in house, reported skin conditions were more common in households < 1 km compared with > 2 km from the nearest gas well (odds ratio = 4.1; 95% CI: 1.4, 12.3; p = 0.01). Upper respiratory symptoms were also more frequently reported in persons living in households < 1 km from gas wells (39%) compared with households 1-2 km or > 2 km from the nearest well (31 and 18%, respectively) (p = 0.004). No equivalent correlation was found between well proximity and other reported groups of respiratory, neurological, cardiovascular, or gastrointestinal conditions.
Although these results should be viewed as hypothesis generating, and the population studied was limited to households with a ground-fed water supply, proximity of natural gas wells may be associated with the prevalence of health symptoms including dermal and respiratory conditions in residents living near natural gas extraction activities. Further study of these associations, including the role of specific air and water exposures, is warranted.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Insulin resistance is associated with nonalcoholic fatty liver disease (NAFLD) and is a major factor in the pathogenesis of type 2 diabetes. The development of hepatic insulin resistance has been ...ascribed to multiple causes, including inflammation, endoplasmic reticulum (ER) stress, and accumulation of hepatocellular lipids in animal models of NAFLD. However, it is unknown whether these same cellular mechanisms link insulin resistance to hepatic steatosis in humans. To examine the cellular mechanisms that link hepatic steatosis to insulin resistance, we comprehensively assessed each of these pathways by using flash-frozen liver biopsies obtained from 37 obese, nondiabetic individuals and correlating key hepatic and plasma markers of inflammation, ER stress, and lipids with the homeostatic model assessment of insulin resistance index. We found that hepatic diacylglycerol (DAG) content in cytoplasmic lipid droplets was the best predictor of insulin resistance (R = 0.80, P < 0.001), and it was responsible for 64% of the variability in insulin sensitivity. Hepatic DAG content was also strongly correlated with activation of hepatic PKCε (R = 0.67, P < 0.001), which impairs insulin signaling. In contrast, there was no significant association between insulin resistance and other putative lipid metabolites or plasma or hepatic markers of inflammation. ER stress markers were only partly correlated with insulin resistance. In conclusion, these data show that hepatic DAG content in lipid droplets is the best predictor of insulin resistance in humans, and they support the hypothesis that NAFLD-associated hepatic insulin resistance is caused by an increase in hepatic DAG content, which results in activation of PKCε.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
OBJECTIVE:To examine moderators and predictors of response to behavior therapy for tics in children and adults with Tourette syndrome and chronic tic disorders.
METHODS:Data from 2 10-week, multisite ...studies (1 in children and 1 in adults; total n = 248) comparing comprehensive behavioral intervention for tics (CBIT) to psychoeducation and supportive therapy (PST) were combined for moderator analyses. Participants (177 male, 71 female) had a mean age of 21.5 ± 13.9 years (range 9–69). Demographic and clinical characteristics, baseline tic-suppressing medication, and co-occurring psychiatric disorders were tested as potential moderators for CBIT vs PST or predictors of outcome regardless of treatment assignment. Main outcomes measures were the Yale Global Tic Severity Scale Total Tic score and the Clinical Global Impression–Improvement score assessed by masked evaluators.
RESULTS:The presence of tic medication significantly moderated response to CBIT vs PST (p = 0.01). Participants showed tic reduction after CBIT regardless of tic medication status, but only participants receiving tic medication showed reduction of tics after PST. Co-occurring psychiatric disorders, age, sex, family functioning, tic characteristics, and treatment expectancy did not moderate response. Across both treatments, greater tic severity (p = 0.005) and positive participant expectancy (p = 0.01) predicted greater tic improvement. Anxiety disorders (p = 0.042) and premonitory urge severity (p = 0.005) predicted lower tic reduction.
CONCLUSIONS:Presence of co-occurring attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, or anxiety disorders did not moderate response to CBIT. Although participants on tic medication showed improvement after CBIT, the difference between CBIT and PST was greater for participants who were not on tic-suppressing medication.
CLINICALTRIALS.GOV IDENTIFIERS:The child and adult CBIT studies are listed on clinical trials.gov (NCT00218777 and NCT00231985, respectively).
CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that CBIT is effective in reducing tic severity across subgroups of patients with chronic tic disorders, although the difference between treatments was smaller for participants on tic-suppressing medications, suggesting reduced efficacy in this subgroup.
Conceptualizing tobacco dependence as a chronic relapsing condition suggests the need to use analytic strategies that reflect that premise. However, clinical trials for smoking cessation typically ...define the primary endpoint as a measure of abstinence at a single timepoint distal to the intervention, typically 3-12 months. This reinforces the concept of tobacco outcomes as a dichotomous state-one is, or is not, abstinent. Fortunately, there are several approaches available to handle longitudinal data that reflect the relapsing and remitting nature of tobacco use during treatment studies. In this paper, sponsored by the Society for Research on Nicotine and Tobacco's Treatment Research Network, we present an introductory overview of these techniques and their application in smoking cessation clinical trials. Topics discussed include models to examine abstinence outcomes (e.g., trajectory models of abstinence, models for transitions in smoking behavior, models for time to event), models that examine reductions in tobacco use, and models to examine joint outcomes (e.g., examining changes in use of more than one tobacco product). Finally, we discuss three additional relevant topics (i.e., heterogeneity of effects, handling missing data, power and sample size) and provide summary information about the type of model that can be used based on the type of data collected and the focus of the study. We encourage investigators to familiarize themselves with these techniques and use them in the analysis of data from clinical trials of smoking cessation treatment. IMPLICATIONS: Clinical trials of tobacco dependence treatment typically measure abstinence 3-12 months after participant enrollment. However, because smoking is a chronic relapsing condition, these measures of intervention success may not accurately reflect the common trajectories of tobacco abstinence and relapse. Several analytical techniques facilitate this type of outcome modeling. This paper is meant to be an introduction to these concepts and techniques to the global nicotine and tobacco research community including which techniques can be used for different research questions with visual summaries of which types of models can be used for different types of data and research questions.
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