Category: Nevin Manimala

J Biopharm Stat. 2022 Jun 8:1-18. doi: 10.1080/10543406.2022.2080696. Online ahead of print.

ABSTRACT

In clinical studies that utilize real-world data, time-to-event outcomes are often germane to scientific questions of interest. Two main obstacles are the presence of non-proportional hazards and confounding bias. Existing methods that could adjust for NPH or confounding bias, but no previous work delineated the complexity of simultaneous adjustments for both. In this paper, a propensity score stratified MaxCombo and weighted Cox model is proposed. This model can adjust for confounding bias and NPH and can be pre-specified when NPH pattern is unknown in advance. The method has robust performance as demonstrated in simulation studies and in a case study.

PMID:35675418 | DOI:10.1080/10543406.2022.2080696

Acta Anaesthesiol Scand. 2022 Jun 8. doi: 10.1111/aas.14101. Online ahead of print.

ABSTRACT

BACKGROUND: In colorectal cancer, surgical resection is fundamental for curative treatment. Epidural analgesia mitigates the perioperative physiologic stress response caused by surgery, and reduction in perioperative stress may reduce postoperative complications. Nevertheless, epidural analgesia also causes hypotension and lower limb motor weakness that can impair postoperative recovery. Here, we aimed to assess the association between epidural analgesia and postoperative complications after colorectal cancer surgery.

METHODS: We identified patients undergoing colorectal cancer surgery 2008-2018 in Denmark in the Danish Colorectal Cancer Group Database and obtained anaesthesia data from the Danish Anaesthesia Database. The Danish National Prescription Registry was used to obtain data on prescriptions filled preoperatively reflecting current comorbidities. Databases were linked using the Danish Central Person Registry number and the operation day. Patients were classified according to preoperative insertion of an epidural catheter for analgesia. Confounders were adjusted by propensity score matching. Logistic regression was used to compute effect estimates of epidural analgesia on postoperative complications.

RESULTS: We identified 19932 individuals undergoing colorectal cancer surgery with available anaesthesia data. Propensity score matching yielded 5691 individuals in each group with balanced preoperative covariates. In the epidural analgesia group 1400 (24.6%) experienced complications compared with 1453 (25.5%) without epidural analgesia. We found no statistically significant association between epidural use and postoperative complications (OR 0.95, 95% CI 0.87-1.04).

CONCLUSION: In total, in this observational study based on Danish registries, we found no association between epidural analgesia and postoperative complications after colorectal cancer surgery.

PMID:35675388 | DOI:10.1111/aas.14101

PLoS One. 2022 Jun 8;17(6):e0268534. doi: 10.1371/journal.pone.0268534. eCollection 2022.

ABSTRACT

BACKGROUND: The clinical implementation of pharmacogenomics (PGx) could be one of the first milestones towards realizing personalized medicine in routine care. However, its widespread adoption requires the availability of suitable clinical decision support (CDS) systems, which is often impeded by the fragmentation or absence of adequate health IT infrastructures. We report results of CDS implementation in the large-scale European research project Ubiquitous Pharmacogenomics (U-PGx), in which PGx CDS was rolled out and evaluated across more than 15 clinical sites in the Netherlands, Spain, Slovenia, Italy, Greece, United Kingdom and Austria, covering a wide variety of healthcare settings.

METHODS: We evaluated the CDS implementation process through qualitative and quantitative process indicators. Quantitative indicators included statistics on generated PGx reports, median time from sampled upload until report delivery and statistics on report retrievals via the mobile-based CDS tool. Adoption of different CDS tools, uptake and usability were further investigated through a user survey among healthcare providers. Results of a risk assessment conducted prior to the implementation process were retrospectively analyzed and compared to actual encountered difficulties and their impact.

RESULTS: As of March 2021, personalized PGx reports were produced from 6884 genotyped samples with a median delivery time of twenty minutes. Out of 131 invited healthcare providers, 65 completed the questionnaire (response rate: 49.6%). Overall satisfaction rates with the different CDS tools varied between 63.6% and 85.2% per tool. Delays in implementation were caused by challenges including institutional factors and complexities in the development of required tools and reference data resources, such as genotype-phenotype mappings.

CONCLUSIONS: We demonstrated the feasibility of implementing a standardized PGx decision support solution in a multinational, multi-language and multi-center setting. Remaining challenges for future wide-scale roll-out include the harmonization of existing PGx information in guidelines and drug labels, the need for strategies to lower the barrier of PGx CDS adoption for healthcare institutions and providers, and easier compliance with regulatory and legal frameworks.

PMID:35675343 | DOI:10.1371/journal.pone.0268534

Genome Biol Evol. 2022 Jun 8:evac088. doi: 10.1093/gbe/evac088. Online ahead of print.

ABSTRACT

As both natural selection and population history can affect genome-wide patterns of variation, disentangling the contributions of each has remained as a major challenge in population genetics. We here discuss historical and recent progress towards this goal – highlighting theoretical and computational challenges that remain to be addressed, as well as inherent difficulties in dealing with model complexity and model violations – and offer thoughts on potentially fruitful next steps.

PMID:35675379 | DOI:10.1093/gbe/evac088

Vet Surg. 2022 Jun 8. doi: 10.1111/vsu.13837. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the mechanical characteristics of a novel angle-stable interlocking nail (NAS-ILN) and compare them to those of a locking compression plate (LCP) by using a gap-fracture model.

STUDY DESIGN: Experimental study.

SAMPLE POPULATION: Synthetic bone models.

METHODS: Synthetic bone models simulating a 50 mm diaphyseal comminuted canine tibial fracture were treated with either a novel angle-stable interlocking nail (NAS-ILN) or a locking compression plate (LCP). Maximal axial deformation and load to failure in compression and 4-point bending, as well as maximal angular deformation, slack, and torque to failure in torsion, were statistically compared (P < .05).

RESULTS: In compression, the maximal axial deformation was lower for NAS-ILN (0.11 mm ± 0.03) than for LCP (1.10 mm ± 0.22) (P < .0001). The ultimate load to failure was higher for NAS-ILN (803.58 N ± 29.52) than for LCP (328.40 N ± 11.01) (P < .0001). In torsion, the maximal angular deformation did not differ between NAS-ILN (22.79° ± 1.48) and LCP (24.36° ± 1.45) (P = .09). The ultimate torque to failure was higher for NAS-ILN (22.45 Nm ± 0.24) than for LCP (19.10 Nm ± 1.36) (P = .001). No slack was observed with NAS-ILN. In 4-point bending, the maximal axial deformation was lower for NAS-ILN (3.19 mm ± 0.49) than for LCP (4.17 mm ± 0.34) (P = .003). The ultimate bending moment was higher for NAS-ILN (25.73 Nm, IQR [23.54-26.86] Nm) than for LCP (16.29 Nm, IQR [15.66-16.47] Nm) (P = .002).

CONCLUSION: The NAS-ILN showed greater stiffness in compression and 4-point bending, and a greater resistance to failure in compression, torsion, and 4-point bending, than LCP.

CLINICAL IMPACT: Based on these results, NAS-ILNs could be considered as alternative implants for the stabilization of comminuted fractures.

PMID:35675144 | DOI:10.1111/vsu.13837

Clin Nucl Med. 2022 Jul 1;47(7):575-582. doi: 10.1097/RLU.0000000000004190. Epub 2022 Apr 27.

ABSTRACT

PURPOSE: Vaccination against coronavirus disease 2019 (COVID-19) is currently under worldwide deployment. The consequences of this vaccination can be seen in radiology and nuclear medicine explorations with visualization of axillary lymph nodes (LNs), as observed on ultrasonography, MRI, or 18F-FDG PET/CT.We aimed to evaluate on PET/CT the incidence of vaccine-related LNs and their characteristics after COVID-19 vaccination, using several radiopharmaceuticals different from 18F-FDG.

PATIENTS AND METHODS: Between February and July 2021, all consecutive patients undergoing a whole-body PET/CT for any indication using a different radiopharmaceutical from 18F-FDG were eligible for inclusion if they had received at least 1 dose of the COVID-19 vaccine. The radiopharmaceutical administered and vaccine type were recorded for each patient. The incidence of positive vaccine-related axillary and supraclavicular LNs on PET/CT was our primary finding, along with the nodes characteristics. Statistical analyses were performed for patients with prostate cancer (PCa) to determine certain interaction factors that were associated with the detection of vaccine-related LNs.

RESULTS: Of the 226 patients in our cohort study, 120 patients underwent an 18F-fluorocholine PET/CT, 79 a 68Ga-PSMA-11 PET/CT, 6 an 18F-FDOPA PET/CT, and 21 a 68Ga-DOTATOC PET/CT. A total of 67.3% of patients (152/226) received BNT162b2mRNA (Pfizer-BioNTech), 26.5% (60/226) ChAdOx1-S (AstraZeneca), 4.9% (11/226) mRNA-1273 (Moderna), and 1.3% (3/226) Ad26.COV2.S (Janssen). The incidence of positive vaccine-related axillary and supraclavicular LNs was 42.5% (51/120 patients) on PET/CT using 18F-fluorocholine and 12.7% (10/79 patients) with 68Ga-PSMA-11. None of our patients undergoing 18F-FDOPA or 68Ga-DOTATOC PET/CT presented any vaccine-related lymphadenopathy. Vaccine-related LNs were statistically associated with the nature of the radiopharmaceutical (P < 10-4), with the number of vaccine doses received (P = 0.041), with a short delay between vaccination and PET/CT realization (P < 10-5), and with a higher prostate-specific antigen level for patients with PCa (P = 0.032), but not with age or vaccine type. The vaccine-related nodes appeared in 85% of the cases, in the 30 days after vaccine injection, were limited in size and uptake, and were most often limited to the axilla level 1 area.

CONCLUSIONS: Detecting positive LNs after COVID-19 vaccination is not an exclusive 18F-FDG PET/CT pattern but is common on 18F-fluorocholine and possible on 68Ga-PSMA-11 PET/CT. Confronting PET/CT findings with clinical data (such as date and site of injection) seems essential in the current pandemic context, just as it does for the radiopharmaceuticals used in PCa to avoid PET/CT misinterpretation and incorrect patient treatment. For 18F-FDOPA or 68Ga-DOTATOC PET/CT, this seems to have a lesser impact.

PMID:35675134 | DOI:10.1097/RLU.0000000000004190

Clin Spine Surg. 2022 Jun 8. doi: 10.1097/BSD.0000000000001351. Online ahead of print.

ABSTRACT

STUDY DESIGN: This was a retrospective case series.

OBJECTIVE: The purpose of this study was to compare radiologic and clinical outcomes in patients with L4-L5 lumbar spinal stenosis (LSS) who had undergone either minimally invasive (MIS-) or open (O-) transforaminal lumbar interbody fusion (TLIF), especially with regard to the development of adjacent segment degeneration (ASDeg).

SUMMARY OF BACKGROUND DATA: ASDeg is defined as the degenerative changes at adjacent segments of a fused segment, with no obvious clinical symptoms.

MATERIALS AND METHODS: A total of 121 LSS patients with a minimum 5-year follow-up were included. Patients were divided into 2 groups according to the surgery performed (MIS-TLIF: 57 patients, O-TLIF: 64 patients). Preoperative and final follow-up radiologic parameters were determined. The incidence of ASDeg was evaluated and compared between the 2 groups. Visual Analog Scale score, Japanese Orthopaedic Association score, and Oswestry Disability Index were used to assess clinical outcomes.

RESULTS: Before surgery, no significant difference was found between MIS-TLIF and O-TLIF groups regarding demographic, radiologic, and clinical data. After a 5-year follow-up, the incidence of ASDeg in LSS patients was 47.1% (57/121). ASDeg was mostly located at the cranial segment of the fused level in each group. The most common type of ASDeg in both groups was intervertebral space collapse. There was a lower chance of ASDeg in MIS-TLIF group than that in O-TLIF group (33.3% vs. 59.4%, P<0.01). Postoperatively, both groups had significant improvement in clinical outcomes, and there were no statistically significant intergroup differences assessed by Visual Analog Scale, Japanese Orthopaedic Association, and Oswestry Disability Index scores.

CONCLUSION: The clinical effect of MIS-TLIF and O-TLIF were similar, but the incidence of ASDeg was significantly lower after MIS-TLIF at 5-year follow-up.

PMID:35675143 | DOI:10.1097/BSD.0000000000001351

J Prosthodont. 2022 Jun 8. doi: 10.1111/jopr.13553. Online ahead of print.

ABSTRACT

PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the effect of using additive manufacturing (AM) for dental ceramic fabrication in comparison with subtractive manufacturing (SM), and to evaluate the effect of the type of AM technology on dental ceramic fabrication.

MATERIALS AND METHODS: A search was conducted electronically in MEDLINE (via PubMed), EBSCOhost, Scopus, and Cochran Library databases, and also by other methods (table of contents screening, backward and forward citations, and grey literature search) up to February 12, 2022, to identify records evaluating additive manufacturing of ceramics for dental purposes in comparison with subtractive manufacturing. A minimum of 2 review authors conducted study selection, quality assessment, and data extraction. Quality assessment was performed with Joanna Briggs Institute tool, and the quantitative synthesis was performed with the Comprehensive Meta-Analysis program (CMA, Biostat Inc). Hedges’s g for effect size was calculated, with 0.2 as small, 0.5 as medium, and 0.8 as large. Heterogeneity was assessed with I² and prediction interval (PI) statistics. Publication bias was investigated with funnel plots and grey literature search. Certainty of evidence was assessed with the Grading of Recommendations: Assessment, Development, and Evaluation (GRADE) tool.

RESULTS: A total of 28 studies were included for the qualitative and quantitative synthesis; 11 in vitro studies on accuracy, 1 in vivo study on color, and 16 in vitro studies on physical and mechanical properties. Meta-analysis showed overall higher accuracy for SM compared with AM, with medium effect size (0.679, CI: 0.173-1.185, p = .009) and also for marginal (g = 1.05, CI: 0.344 to 1.760, p = .004), occlusal (g = 2.24, CI: 0.718 to 3.766, p = .004), and total (g = 4.544, CI: -0.234 to 9.323, p = .062) with large effect size; whereas AM had higher accuracy than SM with small effect size for the external (g = -0.238, CI: -1.215-0.739), p = .633), and internal (g = -0.403, CI: -1.273 to 0.467, p = .364) surfaces. For technology, self-glazed zirconia protocol had the smallest effect size (g = -0.049, CI: -0.878 to 0.78, p = .907), followed by stereolithography (g = 0.305, CI: -0.289 to 0.9, p = .314), and digital light processing (g = 1.819, CI: 0.662 to 2.976, p = .002) technologies. Flexural strength was higher for ceramics made by SM in comparison to AM with large effect size (g = -2.868, CI: -4.371 to -1.365, p< .001). Only 1 study reported on color, favoring ceramics made through AM.

CONCLUSIONS: Subtractive manufacturing had better overall accuracy, particularly for the marginal and occlusal areas, higher flexural strength, and more favorable hardness, fracture toughness, porosity, fatigue, and volumetric shrinkage; whereas AM had more favorable elastic modulus and wettability. Both methods had favorable biocompatibility. All studies on accuracy and mechanical properties were in vitro, with high heterogeneity and low to very low certainty of evidence. There is a lack of studies on color match and esthetics. This article is protected by copyright. All rights reserved.

PMID:35675133 | DOI:10.1111/jopr.13553

Acad Med. 2022 Jun 7. doi: 10.1097/ACM.0000000000004775. Online ahead of print.

ABSTRACT

PURPOSE: As the last examination in the United States Medical Licensing Examination (USMLE) sequence, Step 3 provides a safeguard prior to physicians’ entry into unsupervised practice. There is, however, little validity research focusing on Step 3 scores beyond examining its associations with other educational and professional assessments thought to cover similar content. This study examines the associations between Step 3 scores and subsequent receipt of disciplinary action taken by state medical boards for problematic behavior in practice. It analyzes Step 3 total, Step 3 computer-based case simulation (CCS), and Step 3multiple-choice question (MCQ) scores.

METHOD: The final sample included 275,392 board-certified physicians who graduated from MD-granting medical schools and who passed Step 3 between 2000 and 2017. Cross-classified multilevel logistic regression models were used to examine the effects of Step 3 scores on the likelihood of receiving a disciplinary action, controlling for other USMLE scores and accounting for jurisdiction and specialty.

RESULTS: Results showed that physicians with higher Step 3 total, CCS, and MCQ scores tended to have lower chances of receiving a disciplinary action, after accounting for other USMLE scores. Specifically, a 1-standard-deviation increase in Step 3 total, CCS, and MCQ score was associated with a 23%, 11%, and 17% decrease in the odds of receiving a disciplinary action, respectively.The effect of Step 2 CK score on the likelihood of receiving a disciplinary action was statistically significant, while the effect of Step 1 score became statistically non-significant when other Step scores were included in the analysis.

CONCLUSIONS: Physicians who perform better on Step 3 are less likely to receive a disciplinary action from a state medical board for problematic behavior in practice. These findings provide some validity evidence for the use of Step 3 scores when making medical licensure decisions in the United States.

PMID:35675131 | DOI:10.1097/ACM.0000000000004775

Endocr Relat Cancer. 2022 Jun 1:ERC-22-0115. doi: 10.1530/ERC-22-0115. Online ahead of print.

ABSTRACT

DNA methylation and demethylation regulate the transcription of genes. DNA methylation-associated gene expression of adrenal steroidogenic enzymes may regulate cortisol production in cortisol-producing adenoma (CPA). We aimed to determine the DNA methylation levels of all genes encoding steroidogenic enzymes involved in CPA. Additionally, the aims were to clarify the DNA methylation-associated gene expression and evaluate the difference of CPA genotype from others using DNA methylation data. Twenty-five adrenal CPA and six nonfunctioning adrenocortical adenoma (NFA) samples were analyzed. RNA sequencing and DNA methylation array were performed. The methylation levels at 118 methylation sites of the genes were investigated, and their methylation and mRNA levels were subsequently integrated. Among all the steroidogenic enzyme genes studied, CYP17A1 gene was mainly found to be hypomethylated in CPA compared to that in NFA, and the Benjamini-Hochberg procedure demonstrated that methylation levels at two sites in the CYP17A1 gene body were statistically significant. PRKACA mutant CPAs predominantly exhibited hypomethylation of CYP17A1 gene compared with the GNAS mutant CPAs. Inverse associations between CYP17A1 methylation in three regions of the gene body and its mRNA levels were observed in the NFAs and CPAs. In applying clustering analysis using CYP17A1 methylation and mRNA levels, CPAs with PRKACA mutation were differentiated from NFAs and CPAs with a GNAS mutation. We demonstrated that CPAs exhibited hypomethylation of the CYP17A1 gene body in CPA, especially in the PRKACA mutant CPAs. Methylation of CYP17A1 gene may influence its transcription levels.

PMID:35675123 | DOI:10.1530/ERC-22-0115