Flaws In Study Design Research Articles

Understanding of income and race disparities in hurricane evacuation is contingent upon study case and design

As hurricanes become more frequent and destructive, understanding evacuation decision-making is crucial to refining disaster response strategies. Several studies have explored how socioeconomic characteristics such as income and race impact evacuation behavior. Most of these studies focus on a single hurricane event with the geographic extent limited to one or two states, each using a distinct study design, making them difficult to compare. This raises the question of whether findings from isolated cases can be generalized across different hurricane scenarios and geographical settings under a similar study design and consistent parameter definitions. To address this gap, in this study, we conduct a comparative analysis to understand income and racial disparity across multiple hurricane events. The results indicate that, even with a consistent study design, disparities in evacuation among different socioeconomic groups vary on a case-by-case basis. Furthermore, we show that the study design significantly impacts the observed trends within a single case. This highlights the importance of avoiding generalized conclusions based on limited case studies. It further emphasizes how flawed study designs may fail to capture the complexities of real-world behaviors, thereby leading to suboptimal or ineffective policy recommendations or designs.

Carcinogenic health outcomes associated with endocrine disrupting chemicals exposure in humans: A wide-scope analysis

Endocrine-disrupting chemicals (EDCs) are persistent and pervasive compounds that pose serious risks. Numerous studies have explored the effects of EDCs on human health, among which tumors have been the primary focus. However, because of study design flaws, lack of effective exposure levels of EDCs, and inconsistent population data and findings, it is challenging to draw clear conclusions on the effect of these compounds on tumor-related outcomes. Our study is the first to systematically integrate observational studies and randomized controlled trials from over 20 years and summarize over 300 subgroup associations. We found that most EDCs promote tumor development, and that exposure to residential environmental pollutants may be a major source of pesticide exposure. Furthermore, we found that phytoestrogens exhibit antitumor effects. The findings of this study can aid in the development of global EDCs regulatory health policies and alleviate the severe risks associated with EDCs exposure.

A Systematic Review and Single-Arm Meta-Analysis on the Efficacy of High-Intensity, Focused Ultrasound for Benign Prostatic Hyperplasia Treatment: A Forgotten Option?

Benign prostatic hyperplasia (BPH) is a non-cancerousenlargement of prostate tissue, commonly affecting older men. This condition leads to lower urinary tract symptoms (LUTS), which significantly affect the quality of life. Over time, extensive research has been conducted regarding BPH treatment, exploring various treatment options. High-intensity focused ultrasound (HIFU) is a non-invasive treatment modality that has shown promise in initial studies. However, evidence regarding its long-term efficacy and safety remains inconclusive. This study evaluates HIFU's safety and efficacy for BPH treatment, identifying gaps for future research. The study conducted comprehensive searches across the PubMed, Google Scholar, Cochrane Central, and ClinicalTrials.gov databases, covering English-language articles from 1994 to 2023. Inclusion criteria focused on peer-reviewed studies, with more than 10 patients utilizing ultrasound image-guided HIFU for BPHwhile excluding other HIFU modalities lacking ultrasound image guidance. Data extraction targeted primary outcomes (peak flow rate, International Prostate Symptom Score(IPSS), postvoid residual volume) and secondary outcomes (treatment time, follow-up duration). Statistical analysis utilized a random effects model with heterogeneity assessed by I² statistics and the Q test, alongside subgroup analysis based on study design. The risk of bias assessment employed the Cochrane Collaboration tool for randomized controlled trials and the methodological index for nonrandomized studies. Among 560 identified articles, 12 studies with 522 patients met the inclusion criteria. Primary outcomes showed improvements in Qmax (1 month: 2.50 ml/s, 12 months: 6.22 ml/s) and IPSS (1 month: -9.37 points, 12 months: -11.60 points). Reported complications included transient hematuria, hematospermia, and urinary retention. HIFU presents significant clinical improvements in treating BPH, albeit with slow progression attributed to specific techniques and the ablative approach. Manageable complication profiles are observed, yet study design flaws hinder a comprehensive evaluation of HIFU efficacy. The authors suggest areas for clinical optimization, emphasizing the necessity of further research.

Five aspects of research waste in biomedicine: A scoping review.

The number of published journal articles has grown exponentially during the last 30 years, which may have led to some wasteful research. However, the terminology associated with research waste remains unclear. To address this, we aimed to identify, define, and categorize the aspects of research waste in published biomedical reports. In this scoping review, we systematically searched for biomedical literature reports from 1993 to 2023 in two databases, focusing on those addressing and defining research waste. Through data charting, we analyzed and categorized the aspects of research waste. Based on 4285 initial records in the searches, a total of 832 reports were included in the analysis. The included reports were primarily narrative reviews (26%) and original reports (21%). We categorized research waste into five aspects: methodological, invisible, negligible, underreported, and structural (MINUS) research waste. More than half of the reports (56%) covered methodological research waste concerning flaws in study design, study conduct, or analysis. Invisible research waste covered nonpublication, discontinuation, and lack of data-sharing. Negligible research waste primarily concerned unnecessary repetition, for example, stemming from the absence of preceding a trial with a systematic review of the literature. Underreported research waste mainly included poor reporting, resulting in a lack of transparency. Structural research waste comprised inadequate management, collaboration, prioritization, implementation, and dissemination. MINUS encapsulates the five main aspects of research waste. Recognizing these aspects of research waste is important for addressing and preventing further research waste and thereby ensuring efficient resource allocation and scientific integrity.

Antipsychotic agents in anxiety disorders: An umbrella review.

Although not approved for the treatment of anxiety disorders (except trifluoperazine) there is ongoing off-label, unapproved use of first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) for anxiety disorders. There have been systematic reviews and meta-analyses on the use of antipsychotics in anxiety disorders, most of which focused on SGAs. The specific aims of this umbrella review are to: (1) Evaluate the evidence of efficacy of FGAs and SGAs in anxiety disorders as an adjunctive treatment to traditional antidepressant treatments and other nonantipsychotic medications; (2) Compare monotherapy with antipsychotics to first-line treatments for anxiety disorders in terms of effectiveness, risks, and side effects. The review protocol is registered on PROSPERO (CRD42021237436). An initial search was undertaken to identify systematic reviews and meta-analyses from inception until 2020, with an updated search completed August 2021 and January 2023. The searches were conducted in PubMed, MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), CINAHL Complete (EBSCOhost), and the Cochrane Library through hand searches of references of included articles. Review quality was measured using the AMSTAR-2 (A MeaSurement Tool to Assess Systematic Reviews) scale. The original and updated searches yielded 1796 and 3744 articles respectively, of which 45 were eligible. After final review, 25 systematic reviews and meta-analyses were included in the analysis. Most of the systematic reviews and meta-analyses were deemed low-quality through AMSTAR-2 with only one review being deemed high-quality. In evaluating the monotherapies with antipsychotics compared with first-line treatments for anxiety disorder there was insufficient evidence due to flawed study designs (such as problems with randomization) and small sample sizes within studies. There was limited evidence suggesting efficacy of antipsychotic agents in anxiety disorders other than quetiapine in generalized anxiety disorder (GAD). This umbrella review indicates a lack of high-quality studies of antipsychotics in anxiety disorders outside of the use of quetiapine in GAD. Although potentially effective for anxiety disorders, FGAs and SGAs may have risks and side effects that outweigh their efficacy, although there were limited data. Further long-term and larger-scale studies of antipsychotics in anxiety disorders are needed.

Outcomes following total ankle total talus replacement: A systematic review

BackgroundProsthetic substitution of the talus presents a significant challenge to the foot and ankle surgeon. The shear and compressive forces on the talus and its tenuous blood supply lead to high rates of avascular necrosis and eventual talar collapse. The purpose of this systematic review is to evaluate whether total ankle total talus replacement (TATTR) leads to improved clinical and radiographic outcomes with appropriate safety metrics in patients with a history of avascular necrosis or significant trauma. MethodsWe searched the concepts of talus, prosthesis, and arthroplasty in MEDLINE (PubMed), Embase (Elsevier), CINAHL Complete (EBSCOhost), and Scopus (Elsevier) from the database's inception through March 9, 2023. Inclusion Criteria were 1) previous trauma to the talus, 2) post-traumatic arthritis to the tibiotalar joint, 3) avascular necrosis of talus, 4) multiple failed prior interventions, 5) degenerative osteoarthritis to the tibiotalar joint, and 6) inflammatory arthropathy to tibiotalar joint. Patients less than 18 years of age and manuscripts in non-English languages were excluded. ResultsOf the 7625 references, 16 studies met the inclusion criteria, yielding data from 136 patients (139 ankles). The studies varied in design, with case reports and retrospective case series being predominant. The overall weighted average modified Coleman Methodology Score (mCMS) was 70.4 out of 100, indicating moderate flaws in study design that may be subject to various forms of bias and possible confounders. Demographics showed a diverse range of etiologies, with alumina ceramic being the primary prosthesis material. Functional scores demonstrated improvements in dorsiflexion and plantarflexion, although patient-reported outcome measures (PROs) were inconsistently reported. Complications included fractures, heterotopic ossification, prolonged wound healing, and infections. Revision details were sparsely reported. ConclusionTATTR is a promising treatment modality for improving short-term functional outcomes for patients with avascular necrosis or trauma-related issues. However, this systematic review underscores the need for standardized reporting, longer-term follow-ups, and further research to establish the procedure’s efficacy and safety, particularly in comparison to other treatment modalities. Level of EvidenceIII, Systematic Review of Level IV Studies

Omega-3 Fatty Acid Therapy: A Review of Study Design Flaws, Quality, and Composition

There is marked heterogeneity in the clinical response to omega-3 fatty acid therapy with many authors documenting futility in large-scale trials, secondary re-analysis, and meta-analysis. The question of failure in the context of omega-3 therapy is multifactorial and complicated by the observation that fish intake has been broadly linked to significant risk reductions across a range of conditions. The question that remains is how can we resolve the discrepancy between pre-clinical evidence and epidemiology, which dually emphasize the benefit of omega-3 therapy against the limited success of large-scale clinical trials and smaller scale clinical studies that do not consistently report benefit and may even report harm, especially as it pertains to atrial fibrillation. We present three primary considerations that may clarify the supposed failures of omega-3 therapy: 1) correction for omega-3:omega-6 ratio and competition, 2) variation in the fatty acid composition and quality of omega-3 products, and 3) fundamental concerns pertaining to the omega-3 vehicle and its impact on omega-3 metabolism. While the predominant source of omega-3 therapy is supplements, they are typically not regulated prior to market like drugs and have significant variability in fatty acid composition, vehicle, oxidation, and quality control. Further, the individual response to omega-3 therapy is likely variable and dependent on ambient dietary conditions and inherited differences in endogenous desaturase activity, which has infrequently been accounted for in large studies. The net effect of these concerns should engender pharmaceutical and consumer companies alike to consider 1) refining trial design and 2) consider the role of oxidation in the failure of omega-3 products.

Response to Letter to the Editor "Design Flaws in Study of Prophylaxis of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis" by Feng Liu et al.

Response to Letter to the Editor "Design Flaws in Study of Prophylaxis of Postendoscopic Retrograde Cholangiopancreatography Pancreatitis" by Feng Liu et al.

Conventional niche overlap measurements are not effective for assessing interspecific competition

Interspecific competition is notoriously difficult to detect and quantify, especially in species that are wide-ranging or otherwise difficult to track in the wild. Research investigating interspecific competition usually relies on niche overlap measurements despite that this approach alone does not yield rigorous inference. As an illustration, we review published research assessing interspecific competition in mid-sized carnivores in North America (bobcat – Lynx rufus; Canada lynx – Lynx canadensis; coyote – Canis latrans), and report on shortcomings associated with commonly used study designs and types of inference. Niche overlap measurements typically focus on one or two resources (e.g., food, space, habitat), often using non-independent sampling units and inadequate replication. Few studies measure overlap variation through space, time, or resource variability, which is crucial for robust assessment. Niche overlap (or lack thereof) is used as evidence both for and against interspecific competition, reflecting a weak link between competition theory, predicted responses, and observations. Overall, challenges associated with conducting competition research in the field promote over-reliance on simple measurements, flawed study designs and weak inference. Minimally, niche overlap studies should include assessment across multiple niche dimensions and spatial or temporal variation in competitor density or resource availability. Dynamic investigative approaches should include new technologies for tracking inter-individual interactions, study designs that leverage quasi-experiments (e.g., decline in shared resources, biological control of one competitor), and synthetic analyses (e.g., meta-regression). Ultimately, better understanding of competition theory vis-à-vis study design and data needs will promote improved understanding of the role of interspecific competition in nature.

Resource Allocation Modeling Framework to Refactor Software Design Smells

The domain to study design flaws in the software environment has created enough opportunity for the researchers. These design flaws i.e., code smells, were seen hindering the quality aspects of the software in many ways. Once detected, the segment of the software which was found to be infected with such a flaw has to be passed through some refactoring steps in order to remove it. To know about their working phenomenon in a better way, authors have innovatively talked about the smell detection mechanism using the NHPP modeling framework. Further the authors have also chosen to investigate about the amount of resources/efforts which should be allotted to various code smell categories. The authors have developed an optimization problem for the said purpose which is being validated on the real-life smell data set belonging to an open-source software system. The obtained results are in acceptable range and are justifying the applicability of the model.

The Associate Editor in the peer review process—what's that?

The Associate Editor in the peer review process—what's that?

Updated systematic assessment of human, animal and mechanistic evidence demonstrates lack of human carcinogenicity with consumption of aspartame.

Aspartame has been studied extensively and evaluated for its safety in foods and beverages yet concerns for its potential carcinogenicity have persisted, driven primarily by animal studies conducted at the Ramazzini Institute (RI). To address this controversy, an updated systematic review of available human, animal, and mechanistic data was conducted leveraging critical assessment tools to consider the quality and reliability of data. The evidence base includes 12 animal studies and >40 epidemiological studies reviewed by the World Health Organization which collectively demonstrate a lack of carcinogenic effect associated with any tumor type. Assessment of >1360 mechanistic endpoints, including many guideline-based genotoxicity studies, demonstrate a lack of activity associated with endpoints grouped to key characteristics of carcinogens. Other non-specific mechanistic data (e.g., mixed findings of oxidative stress across study models, tissues, and species) do not provide evidence of a biologically plausible carcinogenic pathway associated with aspartame. Taken together, available evidence supports that aspartame consumption is not carcinogenic in humans and that the inconsistent findings of the RI studies may be explained by flaws in study design and conduct (despite additional analyses to address study limitations), as acknowledged by authoritative bodies.

Real-World Evidence (RWE) Studies Supported Hematologic Oncology United States Food and Drug Administration (US FDA) Approval: What Do They Look like?

Introduction/Background: Although randomized controlled trials are considered the gold standard of evidence for safety and efficacy of a drug, they are subject to several limitations such as difficulty in recruiting patients with rare diseases or randomization of patients to studies with treatments that lack an established standard of care owing to efficacy or toxicity concerns. RWE can help overcome these challenges. RWE collects patient data from historical trials or retrospective observational studies and compares or contextualizes these data to experimental treatments by using proper statistical adjustments. The 21st Century Cures Act inspired the framework for the US FDA to use RWE to assess product effectiveness of approved drugs to support regulatory decision-making. Consequently, RWE is increasingly used in New Drug Applications (NDAs) and Biologics License Applications (BLAs) for hematologic malignancies, and findings suggest that submissions using RWE may receive faster approval. However, data are lacking on adoption of RWE for regulatory submissions and its use in regulatory decision-making. Here, we outline RWE utilization and limitations of regulatory submissions for hematologic malignancy therapeutics, which received accelerated or full approval in the US. Methods: Between 2017 and 2021, all NDA and BLA approvals from the Division of Hematological Malignancies were reviewed for hematology/oncology drugs or indications. The FDA Oncology Drug Advisory Committee (ODAC) briefing and/or multidisciplinary review documents were evaluated to identify the drug approvals using RWE. This assessment was performed by 4 independent reviewers who evaluated FDA comments regarding RWE. RWE sources, study methodology, drug indications, pivotal trial information, statistical analyses, and results were summarized. Results: A total of 74 hematologic malignancy approvals were identified, of which 7 (9.4%) provided RWE that supported regulatory approval. Detailed analyses of the FDA ODAC briefing and/or multidisciplinary review documents for these 7 drug compounds including comparison of trial and RWE data source, patient population, clinical endpoints and outcomes, comparison strategy, and FDA comments are shown in the Table. The FDA identified several key considerations for RWE use for drug applications based on single-arm studies. These included pivotal trials that demonstrated a high response or large treatment effect, an improved drug toxicity profile, or a novel drug mechanism of action. The most common RWE sources included retrospective observational studies from medical records, data from other clinical trials, commercial electronic health record databases, and literature reviews. The most common hematologic indications for RWE submissions were relapsed/refractory (R/R) large B-cell lymphoma and R/R multiple myeloma. The most common endpoints for RWE included presence of measurable residual disease, complete response rate, and duration of response. In contrast, the most common endpoints in pivotal trials included survival endpoints (eg, progression-free survival). The most common statistical methods used to adjust for baseline imbalances included propensity-score matching and inverse-probability of treatment weighting. The FDA identified several areas that may compromise the reliability of RWE: lack of early engagement and discussion of the study design with the FDA, absence of a prespecified statistical analysis plan or protocol, lack of transparency in data collection methods, dissimilar inclusion/exclusion criteria, dissimilar study endpoints, and an inconsistent method or frequency of outcome assessments. Comparator arms often missed baseline covariates, had selection bias, and used different outcome assessment criteria. Conclusion: Good data quality, comparable patient populations, consistent endpoints, prespecified protocols, and the establishment of statistical analysis plans before the start of a study may be the most important factors in the FDA's approval of RWE regulatory submissions. Although the use of RWE to define a direct comparator was limited by flaws in study design and statistical analyses, RWE can be used to establish historical outcomes for patients with currently available treatment. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Accelerated marsh erosion following the Deepwater Horizon oil spill confirmed, ameliorated by planting

Multiple studies have examined the effects of the Deepwater Horizon oil spill on coastal marsh shoreline erosion. Most studies have concluded that the spill increased shoreline erosion (linear retreat) in oiled marshes by ~ 100–200% for at least 2–3 years. However, two studies have called much of this prior research into question, due to potential study design flaws and confounding factors, primarily tropical cyclone influences and differential wave exposure between oiled (impact) and unoiled (reference) sites. Here we confirm that marsh erosion in our field experiment was substantially increased (112–233%) for 2 years in heavily oiled marsh after the spill, likely due to vegetation impacts and reduced soil shear strength attributed to the spill, rather than the influences of hurricanes or wave exposure variation. We discuss how our findings reinforce prior studies, including a wider-scale remote sensing analysis with similar study approach. We also show differences in the degree of erosion among oil spill cleanup treatments. Most importantly, we show that marsh restoration planting can drastically reduce oiled marsh erosion, and that the positive influences of planting can extend beyond the immediate impact of the spill.

Survivorship bias and its implications in dental research and literature

What does the Texan sharpshooter, the World War 2 American air force, The Taj Mahal, cherry farming, and dentistry have in common? They have all been the subject of Survivorship bias. This paper will discuss the concept of survivorship bias in research by using examples of flaws in study designs or interpretation of data. It aims to serve as a caution to practitioners of the need to be aware and critical when reading literature and manufacturers' reports before making decisions regarding materials choices and treatment protocols to follow

Are study populations in trials of antidepressants and psychotherapy comparable? A retrospective case study of two parallel running trials for multi- organ functional somatic disorder

This study retrospectively compares two previous parallel running, randomized, controlled trials of pharmacotherapy (imipramine) and psychotherapy (acceptance and commitment therapy) for multi-organ functional somatic disorder (FSD). Differences in demographics, psychiatric comorbidity, illness severity, and illness duration associated with eligibility for the two trials and patients' willingness to participate are explored using linear or binary regression models. 418 patients with multi-organ FSD was included. We found that 377 (95%) were eligible for psychotherapy and 257 patients (61%) for pharmacotherapy. Patients eligible for pharmacotherapy were less severely impaired, less often received disability pension, reported shorter illness duration and experienced less psychological distress than patients eligible for psychotherapy. Whilst exclusion criteria for both trials differed markedly, it was not possible to clearly identify patient or illness characteristics associated with patients' willingness to participate. The study showed that trial-specific exclusion criteria led to the selection of less complex and less severely impaired patients in the pharmacological trial in this sample of multi-organ FSD. Our findings have important implications for the interpretation and comparability of RCT results of different treatments in multi-organ FSD and may point to some common flaws in study design and interpretation of pharmacological vs. psychotherapeutic intervention trials in psychiatry.

Pharmacogenomics Testing in Phase I Oncology Clinical Trials: Constructive Criticism Is Warranted.

Simple SummaryPhase I clinical trials are a cornerstone of pharmaceutical development in oncology. Many studies have now attempted to incorporate pharmacogenomics into phase I studies; however, many of these studies have fundamental flaws that that preclude interpretation and application of their findings. Study populations are often small and heterogeneous with multiple disease states, multiple dose levels, and prior therapies. Genetic testing typically includes few variants in candidate genes that do no encapsulate the full range of phenotypic variability in protein function. Moreover, a plurality of these studies do not present scientifically robust clinical or preclinical justification for undertaking pharmacogenomics studies. A significant amount of progress in understanding pharmacogenomic variability has occurred since pharmacogenomics approaches first began appearing in the literature. This progress can be immediately leveraged for the vast majority of Phase I studies. The purpose of this review is to summarize the current literature pertaining to Phase I incorporation of pharmacogenomics studies, analyze potential flaws in study design, and suggest approaches that can improve design of future scientific efforts.While over ten-thousand phase I studies are published in oncology, fewer than 1% of these studies stratify patients based on genetic variants that influence pharmacology. Pharmacogenetics-based patient stratification can improve the success of clinical trials by identifying responsive patients who have less potential to develop toxicity; however, the scientific limits imposed by phase I study designs reduce the potential for these studies to make conclusions. We compiled all phase I studies in oncology with pharmacogenetics endpoints (n = 84), evaluating toxicity (n = 42), response or PFS (n = 32), and pharmacokinetics (n = 40). Most of these studies focus on a limited number of agent classes: Topoisomerase inhibitors, antimetabolites, and anti-angiogenesis agents. Eight genotype-directed phase I studies were identified. Phase I studies consist of homogeneous populations with a variety of comorbidities, prior therapies, racial backgrounds, and other factors that confound statistical analysis of pharmacogenetics. Taken together, phase I studies analyzed herein treated small numbers of patients (median, 95% CI = 28, 24–31), evaluated few variants that are known to change phenotype, and provided little justification of pharmacogenetics hypotheses. Future studies should account for these factors during study design to optimize the success of phase I studies and to answer important scientific questions.

Crenotherapy as a Complementary and Integrative Treatment for Chronic Rhinosinusitis: A Systematic Review and Discussion of Current Evidence Limitations.

Chronic rhinosinusitis (CRS) is a common condition that affects patients' quality of life. Standard treatments for CRS have known side effects and variable efficacy rates. Thus, complementary and integrative (CIM) treatments for CRS such as crenotherapy, which utilizes high mineral content water or vapor as an inhalation therapy, are of continued interest. To summarize and evaluate the current research investigating crenotherapy's therapeutic potential and clinical outcomes for the treatment of CRS. Systematic review and qualitative analysis. A systematic review was performed, with a comprehensive search strategy applied to 6 databases from inception to March 2021: CINAHL, Cochrane, Embase, PubMed, Scopus, and Web of Science. Studies with at least 10 patients, which investigated crenotherapy as the sole or adjunctive treatment for CRS in humans were included. In total, 10 articles out of 756 were included. Of these, 6 were randomized controlled trials. The remaining four articles were non-randomized prospective cohort studies. Six studies assessed clinical symptoms in response to crenotherapy, and there were unanimous improvements in Visual Analog Scale (VAS), Sino-Nasal Outcome Test-20 (SNOT-20), and other quality of life metrics. The studies that assessed inflammatory markers, cytology, or other measures showed significant improvement in neutrophil count, spores, ciliary motility, IgE, and manometry. Minimal to no adverse events were reported across all 10 studies. There is limited data to support crenotherapy's effectiveness in treating patients with CRS. However, published studies suggest that for certain patients crenotherapy can both improve CRS symptoms and objective measures of nasociliary function with minimal side effects. Findings must be interpreted with caution due to study heterogeneity, inconsistent use of standard CRS definitions and outcomes measures, as well as other study design flaws. Given these results, as well as a growing interest in CIM, crenotherapy treatments for CRS deserve further investigation.

Religious attendance and global cognitive function: A fixed-effects cross-lagged panel modeling study of older U.S. adults

ObjectivesEvidence linking religious attendance to better cognitive function is based on flawed study designs. No population representative longitudinal studies on the topic have taken both unobserved confounding and reverse causation into account. Recently developed fixed-effects cross-lagged panel modeling (FE-CLPM) offers simultaneous traction on these issues. It also allows parsing of long-from short-run effects. Using FE-CLPM and ten-year data from the Health and Retirement Study—a national probability sample of U.S. adults over age 50—this study began to fill the gaps above. MethodsGender-specific FE-CLPM models were used to examine bidirectional and within-person linkages of religious attendance with global cognitive function. Granger-Sims “causality” tests further examined short-run effects in both directions. Impulse response analysis was used to explore time patterns in these linkages. ResultsAt least among women, religious attendance had negative short-term prospective linkages with global cognitive function. Over successive time points, these associations increased in strength among both genders. Feedback effects—of cognitive status on religious attendance—were found in both women's and men's models, but had a gender-specific pattern. DiscussionResults contradict a large literature positing cognitive benefits of religiosity. Instead, they lend support to a recent “neural resource depletion” model—especially among women. Overall, findings illustrate the “dark side” of religious engagement, which studies increasingly present as a social determinant with “outcome wide” positive effects on multiple health dimensions.

CT/MRI and CEUS LI-RADS Major Features Association with Hepatocellular Carcinoma: Individual Patient Data Meta-Analysis.

Background The Liver Imaging Reporting and Data System (LI-RADS) assigns a risk category for hepatocellular carcinoma (HCC) to imaging observations. Establishing the contributions of major features can inform the diagnostic algorithm. Purpose To perform a systematic review and individual patient data meta-analysis to establish the probability of HCC for each LI-RADS major feature using CT/MRI and contrast-enhanced US (CEUS) LI-RADS in patients at high risk for HCC. Materials and Methods Multiple databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Scopus) were searched for studies from January 2014 to September 2019 that evaluated the accuracy of CT, MRI, and CEUS for HCC detection using LI-RADS (CT/MRI LI-RADS, versions 2014, 2017, and 2018; CEUS LI-RADS, versions 2016 and 2017). Data were centralized. Clustering was addressed at the study and patient levels using mixed models. Adjusted odds ratios (ORs) with 95% CIs were determined for each major feature using multivariable stepwise logistic regression. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) (PROSPERO protocol: CRD42020164486). Results A total of 32 studies were included, with 1170 CT observations, 3341 MRI observations, and 853 CEUS observations. At multivariable analysis of CT/MRI LI-RADS, all major features were associated with HCC, except threshold growth (OR, 1.6; 95% CI: 0.7, 3.6; P = .07). Nonperipheral washout (OR, 13.2; 95% CI: 9.0, 19.2; P = .01) and nonrim arterial phase hyperenhancement (APHE) (OR, 10.3; 95% CI: 6.7, 15.6; P = .01) had stronger associations with HCC than enhancing capsule (OR, 2.4; 95% CI: 1.7, 3.5; P = .03). On CEUS images, APHE (OR, 7.3; 95% CI: 4.6, 11.5; P = .01), late and mild washout (OR, 4.1; 95% CI: 2.6, 6.6; P = .01), and size of at least 20 mm (OR, 1.6; 95% CI: 1.04, 2.5; P = .04) were associated with HCC. Twenty-five studies (78%) had high risk of bias due to reporting ambiguity or study design flaws. Conclusion Most Liver Imaging Reporting and Data System major features had different independent associations with hepatocellular carcinoma; for CT/MRI, arterial phase hyperenhancement and washout had the strongest associations, whereas threshold growth had no association. © RSNA, 2021 Online supplemental material is available for this article.