1-step Approach Research Articles

A new marker predicting gestational diabetes mellitus: First trimester neutrophil/lymphocyte ratio.

Gestational diabetes mellitus (GDM) is a condition that is very common during pregnancy and has negative consequences for both mother and fetus. Insulin resistance has been shown as an important cause in the pathogenesis of GDM and low-level inflammation is suggested to be one of the underlying causes of insulin resistance. We aimed to investigate whether the neutrophil-lymphocyte ratio (NLR), which is an indicator of systemic inflammation, is a predictor for GDM. A total of 228 pregnant women, including 128 GDM (patient group) and 100 healthy pregnant were included in the study. GDM was diagnosed with a 1-step approach between 24 and 28 weeks of pregnancy. We found a significant increase in NLR in the 1st and 3rd trimesters in the GDM group compared to healthy pregnant women, which supports that systemic inflammation starts in the early stages of pregnancy and continues throughout pregnancy. We also reported a positive correlation between NLR and fasting plasma glucose and body mass index in both trimesters. We showed that first trimester NLR independently predicted the development of GDM.

A Cluster Randomized Noninferiority Field Trial of Gestational Diabetes Mellitus Screening

Although it is well-acknowledged that gestational diabetes mellitus (GDM) is associated with the increased risks of adverse pregnancy outcomes, the optimal strategy for screening and diagnosis of GDM is still a matter of debate. This study was conducted to demonstrate the noninferiority of less strict GDM screening criteria compared with the strict International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria with respect to maternal and neonatal outcomes. A cluster randomized noninferiority field trial was conducted on 35 528 pregnant women; they were scheduled to have 2 phases of GDM screening based on 5 different prespecified protocols including fasting plasma glucose in the first trimester with threshold of 5.1 mmol/L (92 mg/dL) (protocols A, D) or 5.6 mmol/L (100 mg/dL) (protocols B, C, E) and either a 1-step (GDM is defined if one of the plasma glucose values is exceeded [protocol A and C] or 2 or more exceeded values are needed [protocol B]) or 2-step approach (protocols D, E) in the second trimester. Guidelines for treatment of GDM were consistent with all protocols. Primary outcomes of the study were the prevalence of macrosomia and primary cesarean section (CS). The null hypothesis that less strict protocols are inferior to protocol A (IADPSG) was tested with a noninferiority margin effect (odds ratio) of 1.7. The percentages of pregnant women diagnosed with GDM and assigned to protocols A, B, C, D, and E were 21.9%, 10.5%, 12.1%, 19.4%, and 8.1%, respectively. Intention-to-treat analyses satisfying the noninferiority of the less strict protocols of B, C, D, and E compared with protocol A. However, noninferiority was not shown for primary CS comparing protocol E with A. The odds ratios (95% CI) for macrosomia and CS were: B (1.01 [0.95-1.08]; 0.85 [0.56-1.28], C (1.03 [0.73-1.47]; 1.16 [0.88-1.51]), D (0.89 [0.68-1.17]; 0.94 [0.61-1.44]), and E (1.05 [0.65-1.69]; 1.33 [0.82-2.00]) vs A. There were no statistically significant differences in the adjusted odds of adverse pregnancy outcomes in the 2-step compared with the 1-step screening approaches, considering multiplicity adjustment. The IADPSG GDM definition significantly increased the prevalence of GDM diagnosis. However, the less strict approaches were not inferior to other criteria in terms of adverse maternal and neonatal outcomes.

A new generation of highly customized Mg alloy-based implants

In the last years, the precision and personalized medicine is pushing the biomedical research efforts towards the direction of implant surgery requiring only 1-step approach: this goal has been achieved after the introduction of resorbable implants. The resorbable prosthetic support is indicated for temporary prosthetic applications, such as bone fractures fixation, or all those conditions usually treated with metal implants then removed with a second surgery, just after the healing of the bone defect. Biodegradable, bioactive and customizable implants for the treatment of bone fractures, both efficient in bearing the functional loads, and showing good biocompatibility and degradation properties matching the bone tissue healing, are still lacking. These premises have led to consider Magnesium (Mg) and its alloys as very promising candidates for the development of temporary, resorbable implants. However, the very high corrosion rate of Mg is the main problem, not yet solved. The material needs to be properly treated/coated, as well as manufactured, in order to design the most suitable duration of the temporary prosthesis permanence in situ. An innovative and interdisciplinary approach has been developed within the M. Era-Net ISIDE project and it is here briefly detailed with a special focus on the highlighted application fields.

Disease Kinetics Measured By Circulating Tumor DNA Correlates with Treatment Response after Tafasitamab in Combination with R-CHOP with or without Lenalidomide in First Line Treatment of DLBCL

Background Currently available clinical and biological prognostic factors do not adequately identify first-line DLBCL patients at risk for treatment failure. In DLBCL, circulating tumor DNA (ctDNA) can be utilized as a for molecular disease classification, detect minimal residual disease (MRD) or predict disease progression. We hypothesized that ctDNA detected by the EuroClonality immunoglobulin-based next generation sequencing (IG-NGS) assay correlates with treatment response and outcome.Patients and methods Overall, 451 samples (41 diagnostic fresh frozen paraffin embedded (FFPE) biopsies, 64 peripheral blood mononuclear cells (PBMC) and 346 plasma samples) from patients from a Phase Ib study in de novo DLBCL treated with tafasitamab and R-CHOP or tafasitamab and R-CHOP in combination with Lenalidomide (First-MIND; MOR208C107) were analyzed. DNA from FFPE or diagnostic PBMC was sequenced by using a 2-step PCR approach with the Euroclonality NGS IGH-VJ, IGH-DJ and IGK primer sets (euroclonality.org) (Brüggemann, Leukemia, 2019) with a number of primers adapted for usage in short fragment cfDNA. IG markers were identified at abundance level ≥5% of annotated IG reads and a >1 log higher abundance to the next most frequent clonotype. Disease related clonotypes were traced in plasma during (C2D1 and C4D1 n=34) and at end of treatment (EOT n=32) by a 1-step PCR approach and sequencing of at least 5000 human genome equivalents (hGE) of cell free (cf)DNA. ctDNA levels were determined as the number of specific clonotype molecules per input genome equivalents normalized by a reference standard DNA spiked into each sample as cIT-QC (Knecht, Leukemia, 2019) and reported per plasma volume. Data were analysed by ARResT/Interrogate (Bystry, Bioinformatics, 2017). Patients were reported MRD positive if ≥1 clonal IG rearrangement was detected.Results From 41 patients with available diagnostic FFPE and sufficient DNA quality for marker screening, 34 (89%) had at least 1 detectable clonal marker (IGH-VJ, IGH-DJ or IGK). One clonal IG marker was identified in 20/34 (59%) patients, whereas two or three markers were identified in 9 (27%) and 5 (14%) patients, respectively. Disease specific clonotypes identified in FFPE were recovered in 11/34 PBMC samples (32%) with a median abundance of 0,29% (range 0.006-21.9%) demonstrating a peripheral blood involvement. In 32/33 (97%) pretreatment plasma samples, ctDNA was detected with a median copy number of 172.5/ml plasma. cfDNA and ctDNA levels prior to treatment correlated with IPI and LDH (Fig1). ctDNA dynamics during treatment demonstrated rapid treatment response at C2D1. 23/34 samples were either MRD neg (n=19) or showed a ctDNA reduction ≥ 2 log levels (Fig2). At C4D1 7/34 (20%) samples had low-level detectable MRD and at EOT 29/32 (91%) patients achieved MRD negativity after treatment with tafasitamab and R-CHOP +/- lenalidomide (LOD 2 x 10 -4 for follow-up samples). Early ctDNA dynamics predicted metabolic response when applying a threshold of ctDNA reduction to <1% after the first treatment cycle. 25/28 (89%) patients completing treatment and achieving PET-response could be identified early during treatment by ctDNA assessment.Conclusion Baseline ctDNA levels determined by the EuroClonality IG-NGS assay and absolute cfDNA amounts correlated with pre-treatment risk factors. ctDNA dynamics after the 1 st treatment cycle demonstrated rapid treatment response to tafasitamab + RCHOP +/- lenalidomide and correlated with metabolic response. Assessment of ctDNA dynamics allows early response assessment and might be useful for risk stratification in patients with DLBCL. [Display omitted] DisclosuresKuffer: Morphosys AG: Current Employment. Blair: Morphosys AG: Current Employment.

1-step screening approach detected more GDM than 2-step approach but did not improve clinical outcomes.

Hillier TA, Pedula KL, Ogasawara KK, et al. A pragmatic, randomized clinical trial of gestational diabetes screening. N Engl J Med. 2021;384:895-904. 33704936.

One-step or 2-step testing for gestational diabetes: which is better?

In the United States, the common approach to detecting gestational diabetes mellitus is the 2-step protocol recommended by the American College of Obstetricians and Gynecologists. A 50 g, 1-hour glucose challenge at 24 to 28 weeks' gestation is followed by a 100 g, 3-hour oral glucose tolerance test when a screening test threshold is exceeded. Notably, 2 or more elevated values diagnose gestational diabetes mellitus. The 2-step screening test is administered without regard to the time of the last meal, providing convenience by eliminating the requirement for fasting. However, depending upon the cutoff used and population risk factors, approximately 15% to 20% of screened women require the 100 g, 3-hour oral glucose tolerance test. The International Association of Diabetes and Pregnancy Study Groups recommends a protocol of no screening test but rather a diagnostic 75 g, 2-hour oral glucose tolerance test. One or more values above threshold diagnose gestational diabetes mellitus. The 1-step approach requires that women be fasting for the test but does not require a second visit and lasts 2 hours rather than 3. Primarily because of needing only a single elevated value, the 1-step approach identifies 18% to 20% of pregnant women as having gestational diabetes mellitus, 2 to 3 times the rate with the 2-step procedure, but lower than the current United States prediabetes rate of 24% in reproductive aged women. The resources needed for the increase in gestational diabetes mellitus are parallel to the resources needed for the increased prediabetes and diabetes in the nonpregnant population. A recent randomized controlled trial sought to assess the relative population benefits of the above 2 approaches to gestational diabetes mellitus screening and diagnosis. The investigators concluded that there was no significant difference between the 2-step screening protocol and 1-step diagnostic testing protocol in their impact on population adverse short-term pregnancy outcomes. An accompanying editorial concluded that perinatal benefits of the 1-step approach to diagnosing gestational diabetes mellitus "appear to be insufficient to justify the associated patient and healthcare costs of broadening the diagnosis." We raise several concerns about this conclusion. The investigators posited that a 20% improvement in adverse outcomes among the entire pregnancy cohort would be necessary to demonstrate an advantage to the 1-step approach and estimated the sample size based on that presumption, which we believe to be unlikely given the number of cases that would be identified. In addition, 27% of the women randomized to the 1-step protocol underwent 2-step testing; 6% of the study cohort had no testing at all. A subset of women assigned to 2-step testing did not meet the criteria for gestational diabetes mellitus but were treated as such because of elevated fasting plasma glucose levels, presumably contributing to the reduction in adverse outcomes but not to the number of gestational diabetes mellitus identified, increasing the apparent efficacy of the 2-step approach. No consideration was given to long-term benefits for mothers and offspring. All these factors may have contributed to obscuring the benefits of 1-step testing; most importantly, the study was not powered to identify what we understand to be the likely impact of 1-step testing on population health.

Fracture toughness of different adhesive/dentin interfaces analyzed by finite element stress analysis

Objectives: Study aimed to assess the fracture toughness of different dentin adhesive approaches and to evaluate the stress distribution at the bond interface during fracture toughness testing by finite element analysis. Materials and Methods: Specimens for chevron-notched beam fracture toughness (CNB) were prepared with dimensions of (3.0 mm × 4.0 mm × 20 mm) according to ISO 24370:2005 standard. Chevron notch was prepared at the adhesive–dentin interface using a highly polished stainless steel spacer. Four different dentin adhesives approaches were used total-etch 3 and 2 step and self-adhesives 2 and 1 step. A total of 60 specimens were prepared for each adhesive approach (n=15). Each specimen was loaded until failure in a 4-point bend test setup and the fracture toughness was calculated according to the ISO specifications. Finite element modeling of the specimens was carried out in order to analyze stress distribution during fracture toughness testing. Data were analyzed by one-way ANOVA followed by tukey‘s post hoc test with significant level at p < 0.001 level (p= 0.0001).. Results: Solobond plus 3-step etch-and-rinse showed the highest mean fracture toughness (1.78 MPam1/2) Whereas, Futurabond M+ 1-step self-etch showed the lowest value (1.13 MPam1/2). These finding were supported by finite element analysis which showed stresses to concentrate at the adhesive–dentin interface during fracture toughness loading and crack propagation. Conclusion: The adhesive approach has a strong effect on the fracture toughness of the adhesive–dentin interface. the 3-step etch-and-rinse approach showing the highest mean fracture toughness while 1-step self-etch approach showing the lowest value.

Sleeve gastrectomy as a rescue of failed gastric banding: comparison of 1- and 2-step approaches.

Series comparing gastric banding (GB) removal and sleeve gastrectomy (SG) when procedures are performed as a 1- or a 2-step approach are contradictory in their outcomes. No series comparing these approaches with midterm weight loss is available. Compare the outcomes and weight loss of SG performed as 1- and 2-step approaches as a revisional procedure for GB failure. University Hospital, France, public practice. Between February 2006 and January 2017, all patients undergoing SG with a previous history of implementation of GB (n = 358) were included in this 2-center, retrospective, observational study. Revisional surgery was proposed in patients with insufficient excess weight loss (excess weight loss ≤50%) or weight regain after GB. A 1-step (1-step group, n = 270) or 2-step (2-step group, n = 88) approach was decided depending on patient's choice and/or surgeon's preference. The primary efficacy endpoint was the comparison of weight loss in the 1- and 2-step groups at the 2-year follow-up. The secondary efficacy endpoints were short-term outcomes (overall mortality and morbidity at postoperative day 30, specific morbidity, reoperation, length of hospital stay, and readmission). In the 1-step group, the mean preoperative body mass index before SG was 40.5 kg/m2 (27.0-69.0), while in the 2-step group, the mean preoperative body mass index was 43.5 kg/m2 (31.5-61.7). Mean operating time was 109 minutes (50-240) in the 1-step group and 78.7 minutes (40-175) in the 2-step group (P = .22). In the 1-step group, 6 conversions to laparotomy occurred, while in the 2-step group, 2 conversions to laparotomy occurred (P = .75). One death (.2%, in the 2-step group) and 39 complications (30 in the 1-step group [11.1%] and 9 in the 2-step group [10.2%]) also occurred. The mean length of hospital stay was 6.2 days in the 1-step group and 4.1 days in the 2-step group. At 2-year follow-up, mean body mass index was 32.4 kg/m2 in the 1-step group and 33.2 kg/m2 in the 2-step group (P = .15), representing excess weight losses of 61.9 and 50.1 (P = .05), respectively. The rates of revisional surgery were .7% and 2.2%, respectively. SG after previous GB is efficient with similar outcomes depending on the 1- or 2-step approach. The 1-step approach seems to have increased weight loss compared with the 2-step approach.

Density functional theory-supported studies of structural and electronicproperties of substituted-phenol derivatives synthesized by efficient O- orC-arylation via Chan–Lam or Suzuki cross-coupling reactions

The present study reports the efficient synthesis and computational studies of the structural and electronic properties of some interesting substituted phenol derivatives. Efficient and versatile procedures to synthesize a series of diaryl ether derivatives (2a-2c, 4a-4h) and bis-arylated products (5a-5c) are described. In this manuscript, using the commercially available starting material 1 and 3, a 1-step approach was developed by means of Cu(II)-mediated Chan-Lam and Pd-catalyzed Suzuki cross-coupling reactions to synthesize diaryl ether and bis-arylated products with moderate to good yields. The starting substrates, 2-bromo-4-methylphenol 1 or 2,4-dibromophenol 3, were both treated with several arylboronic acids, which led to the development of new carbon-oxygen bonds through Chan--Lam reactions. In addition, the hydroxyl group of 2,4-dibromophenol 3 was protected with isopropyl bromide to produce 4, which was then treated with arylboronic acids to synthesize the corresponding bis-arylated products through Suzuki cross-coupling reactions. Density functional theory calculations provided insight into the structural and electronic properties of the synthesized compounds. An analysis of the frontier orbitals and other reactivity descriptors, including the ionization potential, electron affinity, chemical hardness, electronic chemical potential, and electrophilicity index, is presented, which shows that compound 4c was the most reactive, while 4f and h were the most stable.

Everolimus and Long-term Clinical Outcomes in Kidney Transplant Recipients: A Registry-based 10-year Follow-up of 5 Randomized Trials.

Data regarding the long-term efficacy of everolimus-based immunosuppression for kidney transplantation are lacking. Existing randomized controlled trials are limited by short follow-up duration which limits capacity to assess impact on graft and patient survival. We linked individual trial participants to the Australian and New Zealand Dialysis and Transplant Registry. Using a 1-step meta-analysis approach, we investigated the 10-year risk of graft loss, mortality and graft function in 349 participants from 5 randomized trials of everolimus-based immunosuppression. Two hundred forty-two patients randomized to everolimus and 107 control patients were followed for a median of 9 years (interquartile range, 7.1, 9.8 y). There were no significant differences in the risk of all-cause graft loss (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.69-1.94), mortality (adjusted HR, 1.51; 95% CI, 0.78-2.93) and death-censored graft loss in everolimus versus control (adjusted HR, 1.00; 95% CI, 0.50-2.01). For patients in the early initiation (de novo or <6-month conversion) everolimus trials (n = 279), decline in estimated glomerular filtration rate did not significantly differ with control (mean difference in the slope of estimated glomerular filtrate rate, 0.01 mL/min per 1.73 m [-0.06 to +0.09]). This registry-based analysis with long-term follow-up found no differences in graft and recipient survival or graft function for everolimus over current standard of care.

Finding the Optimal Imputation Strategy for Small Cattle Populations.

The imputation from lower density SNP chip genotypes to whole-genome sequence level is an established approach to generate high density genotypes for many individuals. Imputation accuracy is dependent on many factors and for small cattle populations such as the endangered German Black Pied cattle (DSN), determining the optimal imputation strategy is especially challenging since only a low number of high density genotypes is available. In this paper, the accuracy of imputation was explored with regard to (1) phasing of the target population and the reference panel for imputation, (2) comparison of a 1-step imputation approach, where 50 k genotypes are directly imputed to sequence level, to a 2-step imputation approach that used an intermediate step imputing first to 700 k and subsequently to sequence level, (3) the software tools Beagle and Minimac, and (4) the size and composition of the reference panel for imputation. Analyses were performed for 30 DSN and 30 Holstein Frisian cattle available from the 1000 Bull Genomes Project. Imputation accuracy was assessed using a leave-one-out cross validation procedure. We observed that phasing of the target populations and the reference panels affects the imputation accuracy significantly. Minimac reached higher accuracy when imputing using small reference panels, while Beagle performed better with larger reference panels. In contrast to previous research, we found that when a low number of animals is available at the intermediate imputation step, the 1-step imputation approach yielded higher imputation accuracy compared to a 2-step imputation. Overall, the size of the reference panel for imputation is the most important factor leading to higher imputation accuracy, although using a larger reference panel consisting of a related but different breed (Holstein Frisian) significantly reduced imputation accuracy. Our findings provide specific recommendations for populations with a limited number of high density genotyped or sequenced animals available such as DSN. The overall recommendation when imputing a small population are to (1) use a large reference panel of the same breed, (2) use a large reference panel consisting of diverse breeds, or (3) when a large reference panel is not available, we recommend using a smaller same breed reference panel without including a different related breed.

Diabetes and Pregnancy

Diabetes and Pregnancy

76: Maternal and neonatal outcomes in relation to adoption of the 1-step approach to identifying gestational diabetes mellitus

76: Maternal and neonatal outcomes in relation to adoption of the 1-step approach to identifying gestational diabetes mellitus

Rapid Communication: Large exploitable genetic variability exists to shorten age at slaughter in cattle1

Apprehension among consumers is mounting on the efficiency by which cattle convert feedstuffs into human edible protein and energy as well as the consequential effects on the environment. Most (genetic) studies that attempt to address these issues have generally focused on efficiency metrics defined over a certain time period of an animal's life cycle, predominantly the period representing the linear phase of growth. The age at which an animal reaches the carcass specifications for slaughter, however, is also known to vary between breeds; less is known on the extent of the within-breed variability in age at slaughter. Therefore, the objective of the present study was to quantify the phenotypic and genetic variability in the age at which cattle reach a predefined carcass weight and subcutaneous fat cover. A novel trait, labeled here as the deviation in age at slaughter (DAGE), was represented by the unexplained variability from a statistical model, with age at slaughter as the dependent variable and with the fixed effects, among others, of carcass weight and fat score (scale 1 to 15 scored by video image analysis of the carcass at slaughter). Variance components for DAGE were estimated using either a 2-step approach (i.e., the DAGE phenotype derived first and then variance components estimated) or a 1-step approach (i.e., variance components for age at slaughter estimated directly in a mixed model that included the fixed effects of, among others, carcass weight and carcass fat score as well as a random direct additive genetic effect). The raw phenotypic SD in DAGE was 44.2 d. The genetic SD and heritability for DAGE estimated using the 1-step or 2-step models varied from 14.2 to 15.1 d and from 0.23 to 0.26 (SE 0.02), respectively. Assuming the (genetic) variability in the number of days from birth to reaching a desired carcass specifications can be exploited without any associated unfavorable repercussions, considerable potential exists to improve not only the (feed) efficiency of the animal and farm system but also the environmental footprint of the system. The beauty of the approach proposed, relative to strategies that select directly for the feed intake complex and enteric methane emissions, is that data on age at slaughter are generally readily available. Of course, faster gains may potentially be achieved if a dual objective of improving animal efficiency per day coupled with reduced days to slaughter was embarked on.

A retrospective study comparing outcomes in a midwestern US population after introduction of IADPSG guidelines for gestational diabetes

Objective: More evidence is required to endorse the 1-step approach for gestational diabetes mellitus (GDM) for clinical practice. Since 2010, our department has pragmatically allowed faculty to self-select the guidelines they use to screen and diagnose GDM. We sought to compare the maternal and neonatal outcomes from these two simultaneous cohorts. Study design: We performed a retrospective cohort study of all singleton pregnancies delivered between October 2011 and –November 2013 at our hospital. Patients were excluded if they had preexisting diabetes, were not screened or screened inappropriately, or their fetus had congenital anomalies. Patients were grouped by their screening strategy, and maternal and neonatal outcomes were analyzed. Results: The 1-step group had a higher incidence of GDM (21.6% versus 5.0%). Initial results suggested higher rates of neonatal hypoglycemia, phototherapy for hyperbilirubinemia, and a lower rate of gestational HTN. After adjustment, these differences disappeared, but a lower rate of large for gestational age (LGA) infants was discovered (adjusted odds ratios (aOR) 0.78). Conclusion: The picture remains unclear as to whether the 1-step approach is associated with significantly improved outcomes compared with the 2-step approach. We did find a lower risk for a LGA infant in our 1-step cohort, but it is unlikely that the 1-step approach would be cost-effective due to the absence of other improved outcomes.

Complete Calcified Ureteral Stent: A Combined 1-Session Approach

To demonstrate a successful 1-session approach to a complete calcified ureteral stent, preserving the affected kidney without complications. A 33-year-old man presented at our service with an increased urinary frequency, afebrile urinary tract infection, and left lumbar pain. He underwent a ureterolithotripsy with ureteral stenting 3 years ago. After that intervention, he was lost to follow-up. A noncontrast computed tomography scan revealed a complete calcified ureteral stent (FECal V). After careful preoperative planning, the patient was submitted to a combined 1-step approach including left semirigid ureteroscopy, left percutaneous nephrolithotomy, and an open cystolithotomy in supine decubitus. This video demonstrates the surgical steps of the procedure for a FECal V (completely calcified) stent removal. Operative time was 240 minutes. The calcified stent was completely removed. A 6 Fr ureteral catheter and a 16 Fr nephrostomy tube were left at the end of the procedure. No double-J stent was used to avoid the same kind of complication. The patient had no peri- or postoperative complications. A computed tomography scan was performed in the first postoperative day (POD) and revealed 2 small residual fragments (7 mm and 6 mm). The ureteral catheter was removed on the first POD, and the nephrostomy tube on the second POD. The patient was discharged from hospital on the third POD. The patient is now scheduled to a flexible ureteroscopy to treat the small residual fragments. Forgotten ureteral stent is a surgical challenge, requiring multiple approaches and advanced urologic techniques. Our video illustrates that a less invasive and combined 1-step procedure to preserve the kidney is both safe and feasible, when performed by an experienced surgeon.

A General 3-Step Maximum Likelihood Approach to Estimate the Effects of Multiple Latent Categorical Variables on a Distal Outcome

The 3-step approach has been recently advocated over the simultaneous 1-step approach to model a distal outcome predicted by a latent categorical variable. We generalize the 3-step approach to situations where the distal outcome is predicted by multiple and possibly associated latent categorical variables. Although the simultaneous 1-step approach has been criticized, simulation studies have found that the performance of the two approaches is similar in most situations (Bakk & Vermunt, 2016). This is consistent with our findings for a 2-LV extension when all model assumptions are satisfied. Results also indicate that under various degrees of violation of the normality and conditional independence assumption for the distal outcome and indicators, both approaches are subject to bias but the 3-step approach is less sensitive. The differences in estimates using the two approaches are illustrated in an analysis of the effects of various childhood socioeconomic circumstances on body mass index at age 50.

On the Application of the Three-Step Approach to Growth Mixture Models

This series of simulation studies evaluate, in the context of applied research settings, the impact of the parameterization of the covariance structure of the growth mixture model (GMM) on the regression coefficient and standard error estimates in the 3-step method. The results show that the 1-step approach performs better than the 3-step method across the simulation studies. However, the performance of the 3-step method depends slightly or importantly on the parameterization of the GGM from the first step, on the inclusion or not of the predictor at the first step of the analysis, on the population model, and on the type (i.e., logit vs. linear) and size of the regression coefficient estimates.

Combined Whole Body and Multiparametric Prostate Magnetic Resonance Imaging as a 1-Step Approach to the Simultaneous Assessment of Local Recurrence and Metastatic Disease after Radical Prostatectomy

We report our initial experience with whole body and dedicated prostate magnetic resonance imaging as a single examination to assess local recurrence and metastatic disease in patients with suspected recurrent prostate cancer after radical prostatectomy. In this institutional review board approved, retrospective, single center study 76 consecutive patients with clinically suspected recurrent prostate cancer following radical prostatectomy underwent combined whole body and dedicated prostate magnetic resonance imaging at a single session from October 2014 to January 2016. Scans were evaluated to detect disease in the prostate bed and regional nodes, and at distant sites. Comparison was made to other imaging tests, and prostate bed, node and bone biopsies performed within 90 days. Whole body and dedicated prostate magnetic resonance imaging was completed successfully in all patients. Median prostate specific antigen was 0.36 ng/ml (range less than 0.05 to 56.12). Whole body and dedicated prostate magnetic resonance imaging identified suspected disease recurrence in 16 of 76 patients (21%), including local recurrence in the radical prostatectomy bed in 6, nodal metastases in 3, osseous metastases in 4 and multifocal metastatic disease in 3. In 43 patients at least 1 standard staging scan was done in addition to whole body and dedicated prostate magnetic resonance imaging. Concordance was demonstrated between the imaging modalities in 36 of 43 cases (84%). All metastatic lesions detected by other imaging tests were detected on magnetic resonance imaging. In addition, the magnetic resonance imaging modality detected osseous metastases in 4 patients with false-negative findings on other imaging tests, including 2 bone scans and 3 computerized tomography scans. It also excluded osseous disease in 1 patient with positive 18F-fluorodeoxyglucose positron emission tomography/computerized tomography and subsequent negative bone biopsy. Combined whole body and dedicated prostate magnetic resonance imaging is feasible in a clinical practice setting. It can provide incremental information compared to standard imaging in men with suspected prostate cancer recurrence after radical prostatectomy.

Bias-Adjusted Three-Step Latent Markov Modeling With Covariates

Latent Markov models with covariates can be estimated via 1-step maximum likelihood. However, this 1-step approach has various disadvantages, such as that the inclusion of covariates in the model might alter the formation of the latent states and that parameter estimation could become infeasible with large numbers of time points, responses, and covariates. This is why researchers typically prefer performing the analysis in a stepwise manner; that is, they first construct the measurement model, then obtain the latent state classifications, and subsequently study the relationship between covariates and latent state memberships. However, such a stepwise approach yields downward-biased estimates of the covariate effects on initial state and transition probabilities. This article, shows how to overcome this problem using a generalization of the bias-corrected 3-step estimation method proposed for latent class analysis (Asparouhov & Muthén, 2014; Bolck, Croon, & Hagenaars, 2004; Vermunt, 2010). We give a formal derivation of the generalization to latent Markov models and discuss how it can be used with many time points by incorporating it into a Baum–Welch type of expectation-maximization algorithm. We evaluate the method through a simulation study and illustrate it using an application on household financial portfolio change. Our study shows that the proposed correction method yields unbiased parameter estimates and accurate standard errors, except for situations with very poorly separated classes and a small sample.