Randomized controlled trials (RCTs) are considered the gold standard for estimating the effectiveness of a treatment. However, in many instances they are impractical to conduct because of time ...limitations, cost restrictions, or ethical reasons. As a consequence, non-randomized observational studies have an important role in comparative effectiveness and safety research since they can address issues that would not be possible using conventional RCT methodology. Observational studies can be strategically designed to reduce the risk of potential sources of bias by emulating the design principles of an equivalent but ideal randomized trial – the target trial – that would answer the research question of interest.
In this article, we review some of the necessary components of observational studies required for valid causal inference within the framework of target trial emulation, so as to avoid common methodological pitfalls of study design. We discuss the assumptions of consistency, time-zero specification, exchangeability and positivity. To illustrate these concepts in a context where existing knowledge is well-established through clinical trials, we evaluate and compare the treatment effects of vitamin K antagonists (VKA) against no VKA (No VKA) on the treatment of atrial fibrillation from two real-world observational studies, namely the GARFIELD-AF and ORBIT-AF registries. Results are compared with those of published RCTs.
There is limited information on the influence of body mass index (BMI) on clinical outcomes in patients with venous thromboembolism (VTE).
Investigate the influence of BMI on baseline ...characteristics, treatment patterns, and 24-month outcomes in VTE patients.
GARFIELD-VTE is a prospective, non-interventional study of 10 869 patients with objectively confirmed VTE. Patients were grouped according to BMI: <18.5 (underweight; n = 214); 18.5-24.9 (normal; n = 2866); 25.0-29.9 (overweight; n = 3326); ≥30 (obese; n = 3073).
Compared with patients with a normal BMI, obese patients were more frequently Caucasian (77.4% vs. 57.9%), treated in the outpatient setting (30.4% vs. 23.1%), and had previous VTE (17.5% vs. 11.7%). Active cancer was associated with lower BMI (underweight: 30.4%, normal: 13.5%, overweight: 9.4%, obese: 7.0%). At baseline, overweight and obese patients less often received parenteral therapy alone (16.7% and 14.4%) compared with those with an underweight or normal BMI (30.8% and 21.6%). Obese patients more commonly remained on anticoagulants for ≥2-years compared to those with a normal BMI (52.3% vs. 37.7%). After 24-months, the risk of all-cause mortality was lower in overweight and obese patients than in those with normal BMI (adjusted hazard ratio 95% CI; 0.75 0.63-0.89 and 0.59 0.49-0.72, respectively). Underweight patients more often experienced major bleeding (2.45 1.41-4.26) and all-cause mortality (1.90 1.43-2.53) than patients with a normal BMI. Recurrent VTE was comparable among groups.
Underweight VTE patients have the highest risk of mortality and major bleeding. The risk of mortality in obese VTE patients is lower than that in VTE patients with a normal BMI.
The purpose of this study was to assess the diagnostic accuracy of effective atomic number maps reconstructed from dual-energy contrast-enhanced data for discriminating between nonenhancing renal ...cysts and enhancing masses.
Two hundred six patients (128 men, 78 women; mean age, 64 years) underwent a CT renal mass protocol (single-energy unenhanced and dual-energy contrast-enhanced nephrographic imaging) at two different hospitals. For each set of patients, two blinded, independent observers performed measurements on effective atomic number maps from contrast-enhanced dual-energy data. Renal mass assessment on unenhanced and nephrographic images, corroborated by imaging and medical records, was the reference standard. The diagnostic accuracy of effective atomic number maps was assessed with ROC analysis.
Significant differences in mean effective atomic numbers (Z
) were observed between nonenhancing and enhancing masses (set A, 8.19 vs 9.59 Z
; set B, 8.05 vs 9.19 Z
; sets combined, 8.13 vs 9.37 Z
) (p < 0.0001). An effective atomic number value of 8.36 Z
was the optimal threshold, rendering an AUC of 0.92 (95% CI, 0.89-0.94), sensitivity of 90.8% (158/174 95% CI, 85.5-94.7%), specificity of 85.2% (445/522 95% CI, 81.9-88.2%), and overall diagnostic accuracy of 86.6% (603/696 95% CI, 83.9-89.1%).
Nonenhancing renal cysts, including hyperattenuating cysts, can be discriminated from enhancing masses on effective atomic number maps generated from dual-energy contrast-enhanced CT data. This technique may be of clinical usefulness when a CT protocol for comprehensive assessment of renal masses is not available.
Objective
Identify risk factors associated with airway foreign bodies in children in the United States and report observed trends over time.
Data source
KID database (2000‐2009).
Methods
ICD‐9‐CM ...codes for airway foreign bodies were used to identify patients. Risk factors were used for univariate analysis and a multivariate model to identify any increased risk of mortality. These factors were then also trended over time.
Results
Children with airway foreign bodies demonstrate similar risk factors as previously reported, such as male gender, age less than five years and lack of private insurance. The weighted mortality rate for paediatric inpatients with airway foreign bodies was about 2.75%. Fortunately, the rate remained relatively unchanged from 2000 to 2009. Geographically, urban hospital settings appeared to be more affected. Increased risks of mortality were noted for older age, urban hospital setting and teaching hospital status.
Conclusions
Our findings confirm previous findings and identified that the diagnosis of airway foreign bodies in children were associated with male gender, age <5 years, lack of private insurance and geographic location in an urban setting. Further investigation may be warranted to provide clarity on other factors found to have increased association with mortality for quality improvement.
Objective To assess the impact of age at referral on treatment options in craniosynostosis and to identify risk factors for referral delays in this population. Study design A retrospective cohort ...study was performed on patients with an abnormal head shape diagnosis treated at a single academic medical center between January 1, 2004 and January 1, 2014. Newly diagnosed patients with craniosynostosis were identified and referral patterns were examined. A multivariate logistic regression model was used to identify risk factors associated with the range of ages at initial referral. Results A total of 477 patients were evaluated at our institution, 197 of whom were subsequently diagnosed with craniosynostosis. The median age at initial appointment was 5.6 months (mean 8.2 months). Only 28% of children were referred within 3 months of birth. Patients referred within 3 months of birth were less likely to have had preappointment imaging than those patients referred slightly later (OR 2.53, CI 1.07-5.98, P = .035). Several variables were associated with referral after 12 months of age including multiple suture involvement (OR 4.21, CI 1.06-16.68, P = .041), minority race (OR 4.96, CI 1.91-12.9, P ≤ .0001), and referral by a nonpediatrician (OR 6.9, CI 1.73-27.49, P = .006). Conclusions Obtaining imaging before referral to a specialist for abnormal head shape was associated with a delay in evaluation and potentially increases radiation exposure and limits treatment options in patients with craniosynostosis. In addition, children from minority groups, children referred from someone other than a pediatrician's office, and those with multiple suture craniosynostosis are at increased risk of delayed referral. Further studies into the cause of these delays are warranted.
ObjectivesThis study aimed to evaluate the efficacy and safety of finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, on cardiovascular and kidney outcomes by age and/or ...sex.DesignFIDELITY post hoc analysis; median follow-up of 3 years.SettingFIDELITY: a prespecified analysis of the FIDELIO-DKD and FIGARO-DKD trials.ParticipantsAdults with type 2 diabetes and chronic kidney disease receiving optimised renin–angiotensin system inhibitors (N=13 026).InterventionsRandomised 1:1; finerenone or placebo.Primary and secondary outcome measuresCardiovascular (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalisation for heart failure (HHF)) and kidney (kidney failure, sustained ≥57% estimated glomerular filtration rate (eGFR) decline or renal death) composite outcomes.ResultsMean age was 64.8 years; 45.2%, 40.1% and 14.7% were aged <65, 65–74 and ≥75 years, respectively; 69.8% were male. Cardiovascular benefits of finerenone versus placebo were consistent across age (HR 0.94 (95% CI 0.81 to 1.10) (<65 years), HR 0.84 (95% CI 0.73 to 0.98) (65–74 years), HR 0.80 (95% CI 0.65 to 0.99) (≥75 years); Pinteraction=0.42) and sex categories (HR 0.86 (95% CI 0.77 to 0.96) (male), HR 0.89 (95% CI 0.35 to 2.27) (premenopausal female), HR 0.87 (95% CI 0.73 to 1.05) (postmenopausal female); Pinteraction=0.99). Effects on HHF reduction were not modified by age (Pinteraction=0.70) but appeared more pronounced in males (Pinteraction=0.02). Kidney events were reduced with finerenone versus placebo in age groups <65 and 65–74 but not ≥75; no heterogeneity in treatment effect was observed (Pinteraction=0.51). In sex subgroups, finerenone consistently reduced kidney events (Pinteraction=0.85). Finerenone reduced albuminuria and eGFR decline regardless of age and sex. Hyperkalaemia increased with finerenone, but discontinuation rates were <3% across subgroups. Gynaecomastia in males was uncommon across age subgroups and identical between treatment groups.ConclusionsFinerenone improved cardiovascular and kidney composite outcomes with no significant heterogeneity between age and sex subgroups; however, the effect on HHF appeared more pronounced in males. Finerenone demonstrated a similar safety profile across age and sex subgroups.Trial registration numbersNCT02540993, NCT02545049.
Purpose To investigate the relationship between energy level of virtual monoenergetic (VM) imaging and sensitivity in the detection of minimally enhancing renal lesions. Materials and Methods ...Phantoms simulating unenhanced and contrast material-enhanced renal parenchyma were equipped with inserts containing different concentrations of iodine (range, 0-1.15 mg iodine per milliliter). A total of 180 patients (117 men; mean age, 65.2 years ± 13.0 standard deviation) with 194 (62 solid, 132 cystic) renal lesions larger than 10 mm in diameter underwent unenhanced single-energy CT and contrast-enhanced dual-energy CT. VM imaging data sets were created for 70, 80, 90, and 100 keV. Renal lesions were measured, and enhancement was calculated. Area under the receiver operating characteristic curve (AUC) for renal lesion characterization was determined by using the DeLong method. Results The AUC was highest at 70 keV and decreased as energy increased toward 100 keV. AUC in the phantom decreased from 98% (95% confidence interval CI: 95, 100) at 70 keV to 88% (95% CI: 79, 96) at 100 keV (P = .004). AUC in patients decreased from 96% (95% CI: 94, 98) at 70 keV to 79% (95% CI: 71, 86) at 100 keV (P = .001). In patients with an enhancement threshold of 15 HU, sensitivity in the detection of solid renal lesions decreased between from 91% (49 of 62 95% CI: 78, 97) at 70 keV to 48% (33 of 62 95% CI: 25, 71) at 100 keV (P < .05), with no change in specificity (93% 120 of 132 {95% CI: 87, 97} at 70 keV, 97% 125 of 132 {95% CI: 92, 99} at 100 keV). Conclusion There is a reduction in diagnostic accuracy for renal lesion characterization with increasing VM imaging energy. The 70-keV setting may provide an optimal trade-off between sensitivity and specificity.
RSNA, 2018 Online supplemental material is available for this article.
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