Category: Nevin Manimala

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 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

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 Pediatr Gastroenterol Nutr. 2022 Jun 6. doi: 10.1097/MPG.0000000000003510. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine how the use of biological therapy is associated with surgical intervention for paediatric inflammatory bowel disease (PIBD) at population level.

METHODS: Hospital Episode Statistics data were obtained for all admissions within England, (1997-2015), in children aged 0-18 years, with an ICD-10 code for diagnosis of Crohn’s disease (CD), ulcerative colitis (UC) or inflammatory bowel disease-unclassified (IBD-U). OPCS codes for major surgical resection associated with PIBD and for biological therapy were also obtained. Data are presented as median values (interquartile range).

RESULTS: In total, 22,645 children had a diagnosis of PIBD of which 13,722 (61%) had CD, 7,604 (34%) UC and 1,319 (5.8%) cases IBD-U. Biological therapy was used in 4,054 (17.9%) cases. Surgical resection was undertaken in 3,212 (14%) cases, more commonly for CD than UC (17.5 vs 10.3%, p<0.0001). Time from diagnosis to major surgical resection was 8.3 (1.2-28.2) months in CD and 8.2 (0.8-21.3) months in UC. As the time-frame of the data-set progressed, there was a decreased rate of surgical intervention (p=0.04) and an increased use of biological therapy (p<0.0001). Additionally, the number of new diagnoses of PIBD increased.

CONCLUSION: The introduction of biologic agents has been associated with a reduction in cases undergoing surgery in children with a known diagnosis of PIBD. As time progresses we will be able to determine whether biological therapies prevent the need for surgery altogether or just delay this until adulthood.An infographic is available for this article at: http://links.lww.com/MPG/C846.

PMID:35666884 | DOI:10.1097/MPG.0000000000003510

J Pediatr Gastroenterol Nutr. 2022 Jun 6. doi: 10.1097/MPG.0000000000003493. Online ahead of print.

ABSTRACT

OBJECTIVES: We aimed to determine the growth and safety parameters in newborns fed a goat milk based infant formula (GMF) using a randomized double-blind trial, in which a cow milk formula (CMF) served as a control and a breast fed (BF) group as a reference.

METHODS: Healthy term infants (n=218) aged up to 14 days old were recruited from 25 European study centers and randomized to GMF or CMF. Weight, length, head circumference were measured at baseline, and at 14, 28, 56, 84, and 112 days at the study clinics. Adverse events were recorded and stool characteristics, reflux, fussiness, colic, and flatulence were self-reported by parents in 3-day diaries. Anthropometric measurements were transformed to WHO standardized age- and sex adjusted z-scores. Analyses of covariance and linear mixed modeling were used to statistically analyze growth, while adjusting for potential confounders when studying the breast-fed group (n=86).

RESULTS: Comparing the GMF to the CMF group, weight gain [mean difference 227.8 g (95% CI -16.6-439.0)] and z-scores for anthropometric measurements were similar after 112 days intervention. Infant formula groups showed greater mean (SD) weight z-scores than the BF group from 84 days onwards (GMF: 0.28 (0.84), CMF: 0.12 (0.88), BF -0.19 (1.02), p<0.05), whereas length and head circumference z-scores were similar. Incidences of serious adverse events and reflux, fussiness, colic, and flatulence were similar among the three groups.

CONCLUSION: Our data demonstrate that GMF provides adequate growth, has a good tolerability, and is safe to use in infants.

PMID:35666856 | DOI:10.1097/MPG.0000000000003493

Circ Genom Precis Med. 2022 Jun 6:101161CIRCGEN121003612. doi: 10.1161/CIRCGEN.121.003612. Online ahead of print.

ABSTRACT

BACKGROUND: Although many polygenic risk scores (PRS) for cardiovascular traits have been developed in European populations, it is an urgent task to construct a PRS and to evaluate its ability in non-European populations. We developed a genome-wide PRS for blood pressure in a Japanese population and examined the associations between this PRS and hypertension prevalence.

METHODS: We performed a cross-sectional study in 11 252 Japanese individuals who participated in the J-MICC (Japan Multi-Institutional Collaborative Cohort) study. Using publicly available GWAS summary statistics from Biobank Japan, we developed the PRS in the target data (n=7876). With >30 000 single nucleotide polymorphisms, we evaluated PRS performance in the test data (n=3376). Hypertension was defined as systolic blood pressure of 130 mm Hg or more, or diastolic blood pressure of 85 mm Hg or more, or taking an antihypertensive drug.

RESULTS: Compared with the middle PRS quintile, the prevalence of hypertension at the top PRS quintile was higher independently from traditional risk factors (odds ratio, 1.73 [95% CI, 1.32-2.27]). The difference of mean systolic blood pressure and diastolic blood pressure between the middle and the top PRS quintile was 4.55 (95% CI, 2.26-6.85) and 2.32 (95% CI, 0.86-3.78) mm Hg, respectively. Subgroups reflecting combinations of Japanese PRS and modifiable lifestyles and factors (smoking, alcohol intake, sedentary time, and obesity) were associated with the prevalence of hypertension. A European-derived PRS was not associated with hypertension in our participants.

CONCLUSIONS: A PRS for blood pressure was significantly associated with hypertension and BP traits in a general Japanese population. Our findings also highlighted the importance of a combination of PRS and risk factors for identifying high-risk subgroups.

PMID:35666837 | DOI:10.1161/CIRCGEN.121.003612