Category: Statistics

J Pediatr Orthop. 2022 Jul 1;42(6):e696-e700. doi: 10.1097/BPO.0000000000002136. Epub 2022 Mar 10.

ABSTRACT

BACKGROUND: Understanding differences between types of study design (SD) and level of evidence (LOE) are important when selecting research for presentation or publication and determining its potential clinical impact. The purpose of this study was to evaluate interobserver and intraobserver reliability when assigning LOE and SD as well as quantify the impact of a commonly used reference aid on these assessments.

METHODS: Thirty-six accepted abstracts from the Pediatric Orthopaedic Society of North America (POSNA) 2021 annual meeting were selected for this study. Thirteen reviewers from the POSNA Evidence-Based Practice Committee were asked to determine LOE and SD for each abstract, first without any assistance or resources. Four weeks later, abstracts were reviewed again with the guidance of the Journal of Bone and Joint Surgery (JBJS) LOE chart, which is adapted from the Oxford Centre for Evidence-Based Medicine. Interobserver and intraobserver reliability were calculated using Fleiss’ kappa statistic (k). χ2 analysis was used to compare the rate of SD-LOE mismatch between the first and second round of reviews.

RESULTS: Interobserver reliability for LOE improved slightly from fair (k=0.28) to moderate (k=0.43) with use of the JBJS chart. There was better agreement with increasing LOE, with the most frequent disagreement between levels 3 and 4. Interobserver reliability for SD was fair for both rounds 1 (k=0.29) and 2 (k=0.37). Similar to LOE, there was better agreement with stronger SD. Intraobserver reliability was widely variable for both LOE and SD (k=0.10 to 0.92 for both). When matching a selected SD to its associated LOE, the overall rate of correct concordance was 82% in round 1 and 92% in round 2 (P<0.001).

CONCLUSION: Interobserver reliability for LOE and SD was fair to moderate at best, even among experienced reviewers. Use of the JBJS/Oxford chart mildly improved agreement on LOE and resulted in less SD-LOE mismatch, but did not affect agreement on SD.

LEVEL OF EVIDENCE: Level II.

PMID:35667059 | DOI:10.1097/BPO.0000000000002136

J Pediatr Orthop. 2022 Jul 1;42(6):e565-e569. doi: 10.1097/BPO.0000000000002137. Epub 2022 Mar 10.

ABSTRACT

BACKGROUND: A subset of patients successfully treated for developmental dysplasia of the hip (DDH) as infants have symptomatic acetabular dysplasia at skeletal maturity leading to periacetabular osteotomy (PAO). The purpose of this study was to compare femoral and acetabular morphology in PAO patients with late acetabular dysplasia after previous treatment for DDH with PAO patients who do not have a history of DDH treatment.

METHODS: A single surgeon’s patients who underwent PAO between 2011 and 2021 were retrospectively reviewed. Patients previously treated for infantile DDH with a Pavlik harness, abduction brace, closed reduction and spica casting, or open reduction and spica casting were included. Patients with previous bony hip surgery were excluded. Preoperative radiographic measurements of each hip were recorded including lateral center edge angle, anterior center edge angle, and Femoro-Epiphyseal Acetabular Roof index. Computed tomography measurements included the coronal center edge angle, sagittal center edge angle, Tönnis angle, acetabular anteversion at 1, 2, and 3 o’clock, femoral neck-shaft angle, femoral version, and alpha angle. Control PAO cases without a history of DDH diagnosis or treatment were matched with the infantile DDH treatment group in a 2:1 ratio based on coronal center edge angle, age, and sex.

RESULTS: There were 21 hips in 18 patients previously treated for infantile DDH (13 patients Pavlik harness, 3 abduction brace, 1 closed reduction, and 1 open reduction). The control PAO cohort was 42 hips in 42 patients who did not have previous DDH treatment. There was no statistically significant difference in any of the recorded measurements between patients previously treated for DDH and those without previous treatment including femoral version (P=0.494), anteversion at 1 o’clock (P=0.820), anteversion at 2 o’clock (P=0.584), anteversion at 3 o’clock (P=0.137), neck-shaft angle (P=0.612), lateral center edge angle (P=0.433), Femoro-Epiphyseal Acetabular Roof index (P=0.144), and alpha angle (P=0.156).

CONCLUSIONS: Femoral and acetabular morphology is similar between PAO patients with persistent symptomatic acetabular dysplasia following DDH treatment and patients presenting after skeletal maturity with acetabular dysplasia and no previous history of DDH treatment.

LEVEL OF EVIDENCE: Level III-case-control, prognostic study.

PMID:35667051 | DOI:10.1097/BPO.0000000000002137

Blood. 2022 Jun 6:blood.2021015173. doi: 10.1182/blood.2021015173. Online ahead of print.

ABSTRACT

To determine the survival benefit of allogeneic hematopoietic cell transplantation (allo-HCT) in chronic myelomonocytic leukemias (CMML), we assembled a retrospective cohort of CMML patients aged 18-70 years diagnosed between 2000 and 2014 from an International CMML Dataset (ICD, n=730) and from the EBMT registry (n=384). The prognostic impact of allo-HCT was analyzed through univariable and multivariable time-dependent models and with a multi-state model, accounting for age, sex, CMML prognostic scoring system (CPSS low and intermediate-1: lower-risk, intermediate-2 and high: higher-risk) at diagnosis, and AML transformation. In univariable analysis, lower-risk CMMLs had a 5-year OS of 20% (95%CI 12-33%) with allo-HCT versus 42% (95%CI 35-49%) without allo-HCT (P<0.001). In higher-risk patients, 5-year OS was 27% (95%CI 21-34%) with allo-HCT versus 15% (95%CI 11-22%) without allo-HCT (P=0.13). With multi-state models, performing allo-HCT before AML transformation reduced overall survival in patients with lower risk CMML while a survival benefit was predicted for men with higher risk CMML. In a multivariable analysis of lower-risk patients, performing allo-HCT before transformation to AML significantly increased the risk of death within two years of transplantation (HR=3.19, 95%CI 2.30-4.42, P<0.001), with no significant change in long-term survival beyond this time point (HR=0.98, 95%CI 0.58-1.64, P=0.92). In higher risk patients, allo-HCT significantly increased the risk of death in the first two years after transplant (HR=1.46, 95%CI 1.09-1.96, P=0.01), but not beyond (HR=0.60, 95%CI 0.34-1.08, P=0.09). Performing allo-HCT before AML transformation decreases life expectancy in lower risk patients but may be considered in higher risk patients.

PMID:35667047 | DOI:10.1182/blood.2021015173

J Pediatr Orthop. 2022 Jul 1;42(6):e559-e564. doi: 10.1097/BPO.0000000000002151. Epub 2022 Mar 22.

ABSTRACT

BACKGROUND: Clinical and administrative registries provide large volumes of data that can be used for clinical research. However, there are several limitations relating to the quality, consistency, and generalizability of big data. In this study, we aim to compare reported demographics and certain outcomes in patients undergoing posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS), neuromuscular scoliosis (NS), and Scheuermann kyphosis (SK) between 3 commonly utilized databases in pediatric orthopaedic research.

METHODS: We used International Classification of Diseases, Ninth Revision (ICD-9), International Classification of Diseases, 10th Revision (ICD-10), and Current Procedural Terminology (CPT) codes to identify patients in the National Surgical Quality Improvement Program (NSQIP), Healthcare Cost and Utilization Project (HCUP), and Pediatric Health Information System (PHIS) between the ages of 10 to 18 that underwent PSF for AIS, SK, and NS from 2012 to 2015. We compared various demographic factors, such as sex, race/ethnicity, age, and rates of postsurgical infection and 30-day readmissions. Data was analyzed with descriptive and univariate statistics.

RESULTS: We identified 9891 patients that underwent PSF in NSQIP, 10,771 patients in PHIS, and 4335 patients in HCUP over the study period. There were significant differences in patient demographics, readmission rates, and infection rates between all patients that underwent PSF across the databases (P<0.01), as well as specifically in patients with AIS (P<0.01). HCUP had the highest proportion of Hispanic patients that underwent PSF (13.5%), as well as patients who had AIS (13.3%) or NS (17.9%). The PHIS database had the highest proportion of patients undergoing PSF for SK. Among patients with NS, there were significant differences in race across the databases (P<0.01), but no significant differences in sex, ethnicity, or readmission (P>0.05). In addition, there were significant differences in race (P=0.04) and readmission (P=0.01) across databases for patients with SK, but no differences in sex or ethnicity (P>0.05). NSQIP reported the highest rate of 30-day readmissions for patients undergoing PSF (17.9%) compared with other databases (HCUP 4.1%, PHIS 12.1%).

CONCLUSIONS: There are significant differences in patient demographics, sample sizes, and rates of complications for pediatric patients undergoing PSF across 3 commonly utilized US administrative databases. Given the variability in reported outcomes and demographics, generalizability is difficult to extrapolate from these large data sources. In addition, certain databases should be selected to appropriately power studies focusing on particular patient populations or outcomes.

PMID:35667050 | DOI:10.1097/BPO.0000000000002151

Brief Bioinform. 2022 Jun 7:bbac227. doi: 10.1093/bib/bbac227. Online ahead of print.

ABSTRACT

In recent work, researchers have paid considerable attention to the estimation of causal effects in observational studies with a large number of covariates, which makes the unconfoundedness assumption plausible. In this paper, we review propensity score (PS) methods developed in high-dimensional settings and broadly group them into model-based methods that extend models for prediction to causal inference and balance-based methods that combine covariate balancing constraints. We conducted systematic simulation experiments to evaluate these two types of methods, and studied whether the use of balancing constraints further improved estimation performance. Our comparison methods were post-double-selection (PDS), double-index PS (DiPS), outcome-adaptive LASSO (OAL), group LASSO and doubly robust estimation (GLiDeR), high-dimensional covariate balancing PS (hdCBPS), regularized calibrated estimators (RCAL) and approximate residual balancing method (balanceHD). For the four model-based methods, simulation studies showed that GLiDeR was the most stable approach, with high estimation accuracy and precision, followed by PDS, OAL and DiPS. For balance-based methods, hdCBPS performed similarly to GLiDeR in terms of accuracy, and outperformed balanceHD and RCAL. These findings imply that PS methods do not benefit appreciably from covariate balancing constraints in high-dimensional settings. In conclusion, we recommend the preferential use of GLiDeR and hdCBPS approaches for estimating causal effects in high-dimensional settings; however, further studies on the construction of valid confidence intervals are required.

PMID:35667004 | DOI:10.1093/bib/bbac227

J Clin Oncol. 2022 Jun 6:JCO2101393. doi: 10.1200/JCO.21.01393. Online ahead of print.

ABSTRACT

PURPOSE: High levels of circulating tumor plasma cells (CTC-high) in patients with multiple myeloma are a marker of aggressive disease. We aimed to confirm the prognostic impact and identify a possible cutoff value of CTC-high for the prediction of progression-free survival (PFS) and overall survival (OS), in the context of concomitant risk features and minimal residual disease (MRD) achievement.

METHODS: CTC were analyzed at diagnosis with two-tube single-platform flow cytometry (sensitivity 4 × 10^-5) in patients enrolled in the multicenter randomized FORTE clinical trial (ClinicalTrials.gov identifier: NCT02203643). MRD was assessed by second-generation multiparameter flow cytometry (sensitivity 10^-5). We tested different cutoff values in series of multivariate (MV) Cox proportional hazards regression analyses on PFS outcome and selected the value that maximized the Harrell’s C-statistic. We analyzed the impact of CTC on PFS and OS in a MV analysis including baseline features and MRD negativity.

RESULTS: CTC analysis was performed in 401 patients; the median follow-up was 50 months (interquartile range, 45-54 months). There was a modest correlation between the percentage of CTC and bone marrow plasma cells (r = 0.38). We identified an optimal CTC cutoff of 0.07% (approximately 5 cells/µL, C-index 0.64). In MV analysis, CTC-high versus CTC-low patients had significantly shorter PFS (hazard ratio, 2.61; 95% CI, 1.49 to 2.97, P < .001; 4-year PFS 38% v 69%) and OS (hazard ratio, 2.61; 95% CI, 1.49 to 4.56; P < .001; 4-year OS 68% v 92%). The CTC levels, but not the bone marrow plasma cell levels, affected the outcome. The only factor that reduced the negative impact of CTC-high was the achievement of MRD negativity (interaction P = .039).

CONCLUSION: In multiple myeloma, increasing levels of CTC above an optimal cutoff represent an easy-to-assess, robust, and independent high-risk factor. The achievement of MRD negativity is the most important factor that modulates their negative prognostic impact.

PMID:35666982 | DOI:10.1200/JCO.21.01393

Health Aff (Millwood). 2022 Jun;41(6):893-900. doi: 10.1377/hlthaff.2021.01856.

ABSTRACT

The Comprehensive End-Stage Renal Disease (ESRD) Care (CEC) Model was the first Medicare specialty-oriented accountable care organization (ACO) model. We examined whether this model provided better results for beneficiaries with ESRD than primary care-based ACO models. We found significant decreases in Medicare payments ($126 per beneficiary per month), hospitalizations (5 percent), and likelihood of readmissions (8 percent) among beneficiaries with ESRD during the first year of alignment with the CEC Model and no impacts on these measures among beneficiaries with ESRD who were aligned with primary care-based ACOs, relative to fee-for-service Medicare beneficiaries. Neither the CEC nor primary care-based ACO models significantly reduced the likelihood of catheter use, but fistula use increased for CEC Model beneficiaries to levels just above statistical significance. Other populations with chronic conditions may benefit from the testing of a specialty-oriented ACO model. In addition, primary care-based ACOs may benefit from applying CEC Model strategies to high-need subpopulations. Last, the strategies that enabled ESRD Seamless Care Organizations to achieve reductions in hospitalizations and readmissions even without hospital participation as owners could inform physician-led ACOs’ efforts to coordinate with hospitals in their areas.

PMID:35666977 | DOI:10.1377/hlthaff.2021.01856

J Clin Oncol. 2022 Jun 6:JCO2101365. doi: 10.1200/JCO.21.01365. Online ahead of print.

ABSTRACT

PURPOSE: Patients with multiple myeloma (MM) may show patchy bone marrow (BM) infiltration and extramedullary disease. Notwithstanding, quantification of plasma cells (PCs) continues to be performed in BM since the clinical translation of circulating tumor cells (CTCs) remains undefined.

PATIENTS AND METHODS: CTCs were measured in peripheral blood (PB) of 374 patients with newly diagnosed MM enrolled in the GEM2012MENOS65 and GEM2014MAIN trials. Treatment included bortezomib, lenalidomide, and dexamethasone induction followed by autologous transplant, consolidation, and maintenance. Next-generation flow cytometry was used to evaluate CTCs in PB at diagnosis and measurable residual disease (MRD) in BM throughout treatment.

RESULTS: CTCs were detected in 92% (344 of 374) of patients with newly diagnosed MM. The correlation between the percentages of CTCs and BM PCs was modest. Increasing logarithmic percentages of CTCs were associated with inferior progression-free survival (PFS). A cutoff of 0.01% CTCs showed an independent prognostic value (hazard ratio: 2.02; 95% CI, 1.3 to 3.1; P = .001) in multivariable PFS analysis including the International Staging System, lactate dehydrogenase levels, and cytogenetics. The combination of the four prognostic factors significantly improved risk stratification. Outcomes according to the percentage of CTCs and depth of response to treatment showed that patients with undetectable CTCs had exceptional PFS regardless of complete remission and MRD status. In all other cases with detectable CTCs, only achieving MRD negativity (and not complete remission) demonstrated a statistically significant increase in PFS.

CONCLUSION: Evaluation of CTCs in PB outperformed quantification of BM PCs. The detection of ≥ 0.01% CTCs could be a new risk factor in novel staging systems for patients with transplant-eligible MM.

PMID:35666958 | DOI:10.1200/JCO.21.01365

J Exp Psychol Gen. 2022 Jun 6. doi: 10.1037/xge0001225. Online ahead of print.

ABSTRACT

Previous studies showed a bilingual advantage in metacognitive processing (tracking one’s own cognitive performance) in linguistic tasks. However, bilinguals do not constitute a homogeneous population, and it was unclear which aspects of bilingualism affect metacognition. In this project, we tested the hypothesis that simultaneous acquisition and use of typologically different languages leads to development of diverse processing strategies and enhances metacognition. The hypothesis was tested in the visual and auditory modalities in language and nonlanguage domains, in an artificial language learning task. In the auditory modality, the hypothesis was confirmed for linguistic stimuli, with no between-domain transfer of metacognitive abilities was observed at the individual level. In the visual modality, no differences in metacognitive efficiency were observed. Moreover, we found that bilingualism per se and the use of typologically different languages modulated separate metacognitive processes engaged in monitoring cognitive performance in statistical learning task. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35666891 | DOI:10.1037/xge0001225

J Exp Psychol Anim Learn Cogn. 2022 Jun 6. doi: 10.1037/xan0000322. Online ahead of print.

ABSTRACT

Bridging associative and normative theories of animal learning, I show that an associative system can behave as if performing probabilistic inference by using the function f(V) = 1 – e^-cV to transform associative strengths (V) into response probabilities. For example, using this function, an associative system can respond normatively to a compound stimulus AB, given previous separate experiences with the components A and B. The CR probability formulae that result from the proposed function have a normative interpretation in terms of statistical decision theory. The formulae also suggest a normative interpretation of stimulus generalization as a heuristic to infer whether different stimuli are likely to convey redundant or independent information about reinforcement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

PMID:35666932 | DOI:10.1037/xan0000322