Non-randomized Setting Research Articles

Neoadjuvant Chemoimmunotherapy for NSCLC

To date, no meta-analyses have comprehensively assessed the association of neoadjuvant chemoimmunotherapy with clinical outcomes in non-small cell lung cancer (NSCLC) in randomized and nonrandomized settings. In addition, there exists controversy concerning the efficacy of neoadjuvant chemoimmunotherapy for patients with NSCLC with programmed cell death 1 ligand 1 (PD-L1) levels less than 1%. To compare neoadjuvant chemoimmunotherapy with chemotherapy by adverse events and surgical, pathological, and efficacy outcomes using recently published randomized clinical trials and nonrandomized trials. MEDLINE and Embase were systematically searched from January 1, 2013, to October 25, 2023, for all clinical trials of neoadjuvant chemoimmunotherapy and chemotherapy that included at least 10 patients. Observational studies and trials reporting the use of neoadjuvant radiotherapy, including chemoradiotherapy, molecular targeted therapy, or immunotherapy monotherapy, were excluded. Surgical, pathological, and efficacy end points and adverse events were pooled using a random-effects meta-analysis. Among 43 eligible trials comprising 5431 patients (4020 males [74.0%]; median age range, 55-70 years), there were 8 randomized clinical trials with 3387 patients. For randomized clinical trials, pooled overall survival (hazard ratio, 0.65; 95% CI, 0.54-0.79; I2 = 0%), event-free survival (hazard ratio, 0.59; 95% CI, 0.52-0.67; I2 = 14.9%), major pathological response (risk ratio, 3.42; 95% CI, 2.83-4.15; I2 = 31.2%), and complete pathological response (risk ratio, 5.52; 95% CI, 4.25-7.15; I2 = 27.4%) favored neoadjuvant chemoimmunotherapy over neoadjuvant chemotherapy. For patients with baseline tumor PD-L1 levels less than 1%, there was a significant benefit in event-free survival for neoadjuvant chemoimmunotherapy compared with chemotherapy (hazard ratio, 0.74; 95% CI, 0.62-0.89; I2 = 0%). This study found that neoadjuvant chemoimmunotherapy was superior to neoadjuvant chemotherapy across surgical, pathological, and efficacy outcomes. These findings suggest that patients with resectable NSCLC with tumor PD-L1 levels less than 1% may have an event-free survival benefit with neoadjuvant chemoimmunotherapy.

On convergence of occupational measures sets of a discrete-time stochastic control system, with applications to averaging of hybrid systems

We establish that, under certain conditions, the set of random occupational measures generated by the state-control trajectories of a discrete-time stochastic system as well as the set of their mathematical expectations converge to a non-random, convex and compact set. We apply these results to the averaging a hybrid system with a slow continuous-time component and a fast discrete-time component. It is shown that the solutions of the hybrid system are approximated by the solutions of a differential inclusion. The novelty of our results is that we allow the state-control space of the fast component to be non-denumerable.

Universal Difference-in-Differences for Causal Inference in Epidemiology.

Difference-in-differences is undoubtedly one of the most widely used methods for evaluating the causal effect of an intervention in observational (i.e., nonrandomized) settings. The approach is typically used when pre- and postexposure outcome measurements are available, and one can reasonably assume that the association of the unobserved confounder with the outcome has the same absolute magnitude in the two exposure arms and is constant over time; a so-called parallel trends assumption. The parallel trends assumption may not be credible in many practical settings, for example, if the outcome is binary, a count, or polytomous, as well as when an uncontrolled confounder exhibits nonadditive effects on the distribution of the outcome, even if such effects are constant over time. We introduce an alternative approach that replaces the parallel trends assumption with an odds ratio equi-confounding assumption under which an association between treatment and the potential outcome under no treatment is identified with a well-specified generalized linear model relating the pre-exposure outcome and the exposure. Because the proposed method identifies any causal effect that is conceivably identified in the absence of confounding bias, including nonlinear effects such as quantile treatment effects, the approach is aptly called universal difference-in-differences. We describe and illustrate both fully parametric and more robust semiparametric universal difference-in-differences estimators in a real-world application concerning the causal effects of a Zika virus outbreak on birth rate in Brazil. A supplementary digital video is available at: http://links.lww.com/EDE/C90.

Peer effects in subjective performance evaluation

AbstractWe investigate the influence of peer quality on subjective performance evaluation using 75,413 ratings of 130 employees from 6,908 raters in a business school setting. We find that subjective performance ratings are lower for employees with higher quality peer groups in both randomized and nonrandomized settings. Using a novel long‐window setting, we observe peer effects persisting, but slowly decaying, for several months even when priming raters with the employees' previous performance information. We find that the strength of the peer effects is greater for focal employees with weaker performance, for the peers with higher attribute similarity, and when the performance of peers is more extreme. Overall, we find strong and persistent peer effects in subjective performance evaluation.

Clinical outcomes in end stage renal disease on dialysis and severe coronary artery disease: A real-world study

BackgroundThe optimal management of patients with end-stage renal disease (ESRD) on dialysis with severe coronary artery disease (CAD) has not been determined. MethodsBetween 2013 and 2017, all patients with ESRD on dialysis who had left main (LM) disease, triple vessel disease (TVD) and/or severe CAD for consideration of coronary artery bypass graft (CABG) were included. Patients were divided into 3 groups based on final treatment modality: CABG, percutaneous coronary intervention (PCI), optimal medical therapy (OMT). Outcome measures include in-hospital, 180-day, 1-year and overall mortality and major adverse cardiac events (MACE). ResultsIn total, 418 patients were included (CABG 11.0%, PCI 65.6%, OMT 23.4%). Overall, 1-year mortality and MACE rates were 27.5% and 55.0% respectively. Patients who underwent CABG were significantly younger, more likely to have LM disease and have no prior heart failure. In this non-randomized setting, treatment modality did not impact on 1-year mortality, although the CABG group had significantly lower 1-year MACE rates (CABG 32.6%, PCI 57.3%, OMT 59.2%; CABG vs. OMT p < 0.01, CABG vs. PCI p < 0.001). Independent predictors of overall mortality include STEMI presentation (HR 2.31, 95% CI 1.38–3.86), prior heart failure (HR 1.84, 95% CI 1.22–2.75), LM disease (HR 1.71, 95% CI 1.26–2.31), NSTE-ACS presentation (HR 1.40, 95% CI 1.03–1.91) and increased age (HR 1.02, 95% CI 1.01–1.04). ConclusionTreatment decisions for patients with severe CAD with ESRD on dialysis are complex. Understanding independent predictors of mortality and MACE in specific treatment subgroups may provide valuable insights into the selection of optimal treatment options.

The Impact of Physics Education Technology (PhET) Interactive Simulation-Based Learning on Motivation and Academic Achievement Among Malawian Physics Students.

The online version contains supplementary material available at 10.1007/s10956-022-10010-3.

The Landscape of Maintenance Therapy Trials Following Autologous Transplant for Multiple Myeloma

BACKGROUND: The current standard for maintenance therapy following autologous stem cell transplant (ASCT) in patients with multiple myeloma (MM) is lenalidomide, an oral treatment with demonstrated overall survival benefit. Other options for MM may incur toxicities or require frequent visits to infusion centers and may thus not be best suited as maintenance. Patients with high-risk cytogenetic features have poorer outcomes than those considered to have standard risk disease, and national guidelines recommend doublet maintenance (with a proteasome inhibitor and lenalidomide in this setting). Currently, the role of minimal residual disease (MRD) in treatment decision making is unknown but MRD status in this setting may dictate treatment discontinuation in the future. We conducted a review of currently enrolling clinical trials to characterize therapeutic agents/strategies being used or evaluated in a maintenance setting, outcomes evaluated, the inclusion of high-risk patients, and the use of MRD response in guiding management decisions. METHODS: A comprehensive search was performed on the clinicaltrials.gov, clinicaltrialsregister.eu, and anzctr.org.au databases on March 2, 2022, using the keywords "newly diagnosed multiple myeloma", "transplant eligible multiple myeloma", and "maintenance in multiple myeloma". Only studies that were currently recruiting patients, or those listed as active but not yet recruiting were included. Studies that completed enrollment, were terminated, or had been presented or published were not included. Studies were included if patients were planned to undergo autologous stem cell transplant after induction therapy followed by maintenance strategy. If at least one arm received post-transplant maintenance therapy, and the maintenance therapy was specified in the trial description, it was included. Trials evaluating maintenance therapy after a salvage transplant or maintenance therapy in non-transplant settings were excluded. RESULTS: A total of 20 studies were analyzed. Table 1 highlights characteristics. Of the 20 studies, 11 (55.0%) were randomized and 9 (45.0%) were non-randomized. Six studies (30.0%) evaluated PFS as a primary outcome, and 2 studies (10.0%) included OS as a primary outcome. Four of the 20 (20.0%) studies included multiple primary endpoints in addition to time to event outcome, while 4 (20.0%) had a time to event outcome as the sole primary outcome being investigated. Of the 11 randomized studies, 2 studies evaluated OS (18.1%) and 5 evaluated PFS (45.5%) as primary endpoint. MRD negativity was included as a primary endpoint in 11 studies (55.0%) and a secondary endpoint in seven (35%). Of the 9 nonrandomized studies, 4 had a primary endpoint of MRD negativity rate (44.4%), 2 (22.2%) had response-based primary outcomes, and one (11.1%) had a time to event primary outcome. Of the total trials, two (10.0%) assessed or mandated discontinuation of maintenance therapy for those achieving MRD negativity. Table 2 describes maintenance regimens utilized. A total of 4 randomized studies assessed comparison of lenalidomide and another agent to lenalidomide alone with a primary endpoint powered for PFS/OS. Only one study limited enrollment to standard risk disease. No studies enrolled only "high-risk" disease. Amongst a total of 19 trials enrolling patients with high-risk disease, eight trials (42.1%) were offering or permitting patients with high-risk disease to receive single agent lenalidomide. CONCLUSION: Our study analyzing the landscape of current maintenance trials demonstrates that there are many promising clinical trial designs that adapt treatment based on the depth of responses and incorporate newer agents with enough statistical power to demonstrate OS advantage. However, there remains room for improvement, as evidenced by trials evaluating drugs with marked toxicity profiles in non-randomized single arm settings, patients with high-risk disease being permitted to receive treatment that may be inferior to what current guidelines recommend, and a lack of patient centered endpoints (such as OS or quality of life) being evaluated as primary endpoints. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Predictors of long-term clinical outcomes in adult patients after lumbar total disc replacement: development and validation of a prediction model.

Long-term outcomes of single-level lumbar arthroplasty are understood to be very good, with the most recent Investigational Device Exemption (IDE) trial showing a < 5% reoperation rate at the close of the 7-year study. This post hoc analysis was conducted to determine whether specific patients from the activL IDE data set had better outcomes than the mean good outcome of the IDE trial, as well as to identify contributing factors that could be optimized in real-world use. Univariable and multivariable logistic regression models were developed using the randomized patient set (n = 283) from the activL trial and used to identify predictive factors and to derive risk equations. The models were internally validated using the randomized patient set and externally validated using the nonrandomized patient set (n = 52) from the activL trial. Predictive power was assessed using area under the receiver operating characteristic curve analysis. Two factors were significantly associated with achievement of better than the mean outcomes at 7 years. Randomization to receive the activL device was positively associated with better than the mean visual analog scale (VAS)-back pain and Oswestry Disability Index (ODI) scores, whereas preoperative narcotics use was negatively associated with better than the mean ODI score. Preoperative narcotics use was also negatively associated with return to unrestricted full-time work. Other preoperative factors associated with positive outcomes included unrestricted full-time work, working manual labor after index back injury, and decreasing disc height. Older age, greater VAS-leg pain score, greater ODI score, female sex, and working manual labor before back injury were identified as preoperative factors associated with negative outcomes. Preoperative BMI, VAS-back pain score, back pain duration ≥ 1 year, SF-36 physical component summary score, and recreational activity had no effect on outcomes. Lumbar total disc replacement for symptomatic single-level lumbar degenerative disc disease is a well-established option for improving long-term patient outcomes. Discontinuing narcotics use may further improve patient outcomes, as this analysis identified associations between no preoperative narcotics use and better ODI score relative to the mean score of the activL trial at 7 years and increased likelihood of return to work within 7 years. Other preoperative factors that may further improve outcomes included unrestricted full-time work, working manual labor despite back injury, sedentary work status before back injury, and randomization to receive the activL device. Tailoring patient care before total disc replacement may further improve patient outcomes.

Use of Propensity Scoring and Its Application to Real-World Data: Advantages, Disadvantages, and Methodological Objectives Explained to Researchers Without Using Mathematical Equations.

Real-time data collection of patient health status and medications is sped up with modern electronic devices and technologies. As real-world data provide enormous research opportunities, propensity score (PS) methods have been getting attention due to their theoretical grounds in a nonrandomized study setting. In contrast to randomized clinical trials, observational clinical data obtained from a real-world database may not have balanced distributions of patient characteristics between treatment and control groups at the beginning of the respective study. These imbalanced distributions may cause a bias in an estimated treatment effect, which needs to be eliminated. Propensity scoring is one class of statistical methods to address the imbalance issue of real-world data sets. This article provides basic concepts and assesses advantages, disadvantages, and methodological objectives of propensity scoring. Targeting clinical pharmacology researchers with limited statistical background, 5 representative methods are reviewed and visualized: matching, stratification, covariate modeling, inverse probability of treatment weighting, and doubly robust methods. Examples of applications of PS methods were selected from the literature of outcomes research and drug development, nephrology, and pediatrics. Opportunities of applications related to these examples are described. Furthermore, potential future applications of PS methods in clinical pharmacology are discussed. The 21st Century Cures Act signed in 2016 encourages scientists to find opportunities to apply propensity scoring to real-world data. This article underscores that scientists need to justify their choice of statistical methods, whether a PS method or an alternative method, based on their clinical study design, statistical assumptions, and research objectives.

Long-term prediction of mortality and comparative treatment benefit following percutaneous or surgical revascularization

Abstract Background The SYNTAX score II 2020 (SSII-2020), which was derived and externally validated from randomized trials, was designed to predict death following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with three-vessel disease and/or left main disease. We aimed to investigate its value in identifying the safest modality of revascularization in a non-randomized setting. Methods Five-year mortality was assessed in 7362 patients with three-vessel disease and/or left main disease enrolled in a Japanese PCI/CABG registry. New-generation drug eluting stents and imaging guidance became the default PCI strategy during enrolment of the last cohort. The discriminative ability of the SSII-2020 for 5-year mortality was assessed using Harrell's C statistic (C-index). Agreement between observed and predicted rates of all-cause mortality following either PCI or CABG and treatment benefit (absolute risk difference) for this outcome were assessed by calibration plots. Results The SSII-2020 had helpful discrimination (C-index = 0.72) and good calibration (intercept = −0.11, slope = 0.92) for 5-year mortality. The absolute risk difference in mortality between CABG and PCI (treatment benefit) was well calibrated when the whole population was grouped into quarters according to the predicted absolute risk difference of 5-year mortality. The observed differences in survival in favor of CABG were 4.2% (0.1 to 8.2%, log-rank p=0.05) and 8.5% (3.8 to 13.2%, log-rank p&amp;lt;0.01) in the respective third and fourth quarters. In contrast, the observed differences in survival were not significantly different in either the first (3.0% [−0.8 to 6.8%, log-rank p=0.12]) or the second quarter (1.3% [−2.4 to 5.1%, log-rank p=0.39]). Conclusions The SSII-2020 is well able to predict death at 5 years – and the mortality difference between PCI and CABG, and therefore has the potential to support decision making on revascularization in patients with three-vessel disease and/or left main coronary artery disease. Funding Acknowledgement Type of funding sources: None.

Development and validation of prognostic scoring in primary intestinal diffuse large B-cell lymphoma: a single-institution study of 184 patients.

BackgroundThe incidence of primary intestinal diffuse large B-cell lymphoma (PI-DLBCL) is much lower than primary gastric DLBCL, and large-scale analyses on the clinical characteristics, molecular features, therapeutic strategies, and risk stratification have been seldomly performed in PI-DLBCL.MethodsTo assess prognostic model development, 107 PI-DLBCL patients diagnosed before 2014 were studied for prognosis factors including different primary involved sites and treatment strategies. For internal validation, a non-random split sample set with 77 PI-DLBCL patients after 2014 was included for validation of the prognosis factors.ResultsPatients with an ileocecal lesion presented with better survival time than those with non-ileocecal sites, with surgical resection significantly influencing the prognosis. Non-ileocecal patients who underwent surgery with lymphadenectomy had superior overall survival (OS) and progression-free survival (PFS) compared to those receiving surgery without lymphadenectomy or those not receiving (without) surgery. For ileocecal patients, surgery with or without lymphadenectomy resulted in better OS and PFS than those without surgery. For biomarker analysis, only BCL-2 >50% or Ki67 >80% on tumor cells indicated poor clinical outcome. In multivariate analysis, age, Eastern Cooperative Oncology Group (ECOG) score, and site of origin were independent prognostic factors for inferior OS in PI-DLBCL. A prognosis model was set up based on age, ECOG score, and site of origin, and validated well.ConclusionsThe prognosis in patients with PI-DLBCL with ileocecal involvement showed was better than those with non-ileocecal involvement. Surgical strategy can impact the clinical outcome of PI-DLBCL patients.

External Validation of the SYNTAX Score II 2020

BackgroundThe SYNTAX score II 2020 (SSII-2020) was derived from cross correlation and externally validated in randomized trials to predict death and major adverse cardiac and cerebrovascular events (MACE) following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) in patients with 3-vessel disease (3VD) and/or left main coronary artery disease (LMCAD). ObjectivesThe authors aimed to investigate the SSII-2020’s value in identifying the safest modality of revascularization in a non-randomized setting. MethodsFive-year mortality and MACE were assessed in 7,362 patients with 3VD and/or LMCAD enrolled in a Japanese PCI/CABG registry. The discriminative abilities of the SSII-2020 were assessed using Harrell’s C statistic. Agreement between observed and predicted event rates following PCI or CABG and treatment benefit (absolute risk difference [ARD]) for these outcomes were assessed by calibration plots. ResultsThe SSII-2020 for 5-year mortality well predicted the prognosis after PCI and CABG (C-index = 0.72, intercept = −0.11, slope = 0.92). When patients were grouped according to the predicted 5-year mortality ARD, <4.5% (equipoise of PCI and CABG) and ≥4.5% (CABG better), the observed mortality rates after PCI and CABG were not significantly different in patients with lower predicted ARD (observed ARD: 2.1% [95% CI: −0.4% to 4.4%]), and the significant difference in survival in favor of CABG was observed in patients with higher predicted ARD (observed ARD: 9.7% [95% CI: 6.1%-13.3%]). For MACE, the SSII-2020 could not recommend a specific treatment with sufficient accuracy. ConclusionsThe SSII-2020 for predicting 5-year death has the potential to support decision making on revascularization in patients with 3VD and/or LMCAD.

Secondary Analysis of a Study on Exercise Therapy in Hip Osteoarthritis: Follow-Up Data on Pain and Physical Functioning.

We evaluated the short- and longer-term effects of exercise therapy in hip osteoarthritis patients (OA) at baseline, three, six, and 12 months in a randomized setting, followed by a non-randomized setting. The primary randomized intervention (E = exercise, P = placebo–ultrasound, C = control) was followed by a voluntary three-month exercise therapy for P and C (renamed P-E, C-E). Participants randomized to E were not offered treatment again (E-C). Effect sizes (ES; 95% CI) were calculated for within-group effects across time for bodily pain (SF-36) and WOMAC pain, function, and stiffness. ANCOVAs of post-treatment scores were used for group comparison after the group-specific exercise intervention phase. Exercise adherence was assessed and related to post-treatment scores of clinical outcomes. Data of 115 participants of the RCT eligible for follow-up and completing exercise therapy were included into our analyses. Small to medium beneficial long-term effects of cumulative interventional effects, including exercise training, persisted in all groups. Group E-C (n = 49) showed significant 12 months vs. baseline within-group ES in all outcomes (ES 0.39–0.59) except stiffness. Findings were less prominent for exercise therapy in a non-randomized setting (C-E, P-E, both n = 33). Differences are partially explained by adherence rates, highlighting the relevance of therapy compliance strategies. Short-term between-group differences (ANCOVAs) only showed statistically significant differences for WOMAC function between P-E and E-C in favor of E-C (6.4 (95% CI 1.6–11.2; score range 0–100)).

Improving postoperative outcome in rectal cancer surgery: Enhanced Recovery After Surgery in an era of increasing laparoscopic resection.

The Enhanced Recovery After Surgery (ERAS) protocol reduces complications and length of stay (LOS) in colon cancer, but implementation in rectal cancer is different because of neo-adjuvant therapy and surgical differences. Laparoscopic resection may further improve outcome. The aim of this study was to evaluate the effects of introducing ERAS on postoperative outcome after rectal cancer resection in an era of increasing laparoscopic resections. Patients who underwent elective rectal cancer surgery from 2009 till 2015 were included in this observational cohort study. In 2010, ERAS was introduced and adherence to the protocol was registered. Open and laparoscopic resections were compared. With regression analysis, predictive factors for postoperative outcome and LOS were identified. A total of 499 patients were included. The LOS decreased from 12.3days in 2009 to 5.7days in 2015 (p = 0.000). Surgical site infections were reduced from 24% in 2009 to 5% in 2015 (p = 0.013) and postoperative ileus from 39% in 2009 to 6% in 2015 (p = 0.000). Only postoperative ERAS items and laparoscopic surgery were associated with an improved postoperative outcome and shorter LOS. ERAS proved to be feasible, safe, and contributed to improving short-term outcome in rectal cancer resections. The benefits of laparoscopic surgery may in part be explained by reaching better ERAS adherence rates. However, the laparoscopic approach was also associated with anastomotic leakage. Despite the potential of bias, this study provides an insight in effects of ERAS and laparoscopic surgery in a non-randomized real-time setting.

Nest site selection and nesting behavior of the mud turtle Kinosternon scorpiodes (Testudines, Kinosternidae) in Palo Verde National Park, Costa Rica: implications for management

Habitat selection is the process whereby individuals preferentially use, or occupy, a non-random set of available habitats. At the same time, nest site selection is defined as the placement of eggs by females at sites differing from random sites within a delimited area. We located 59 nests of the mud turtle Kinosternon scorpioides in Palo Verde National Park (PVNP) in Northwestern Costa Rica. We compared eight microhabitat variables at nest sites against those at random sites. Females significantly placed their eggs at sites with more understory, leaf litter cover, and greater leaf litter depth than in random sites. Additionally, females selected sites with lower air and soil temperature and lower air humidity. Palo Verde NP is subject to active management actions designed to control invasive plant species in the wetland, namely cattail (Thypha domingensis Pers.). The main actions have been cattle grazing, controlled fires, and mechanical crushing of vegetation. We found that habitat quality in nesting areas is being threatened by at least one of these actions: cattle grazing. This is detrimental for three microhabitat traits that turtles select for nesting sites: understory cover, leaf litter cover, and leaf litter depth. The continued degradation of microhabitats at nesting areas of K. scorpioides at PVNP could be affecting recruitment due to embryo survivorship.

Minor bleeding in patients with atrial fibrillation using a non-vitamin-K antagonist oral anticoagulant

Aims We sought to investigate the magnitude of minor bleeding and identify risk factors for minor bleeds during non-vitamin-K antagonist oral anticoagulant (NOAC) therapy. Methods This was an observational cohort study of patients with atrial fibrillation (AF) referred to a regional NOAC outpatient clinic between February 2013 and October 2017. The study population consisted of 875 consecutive patients with AF who visited the NOAC outpatient unit to initiate treatment with apixaban (N = 303), dabigatran (N = 267) or rivaroxaban (N = 305) for long-term ischemic stroke prophylaxis. Minor bleed was defined as every overt bleeding that does not fulfil the criteria of major or non-major clinically relevant bleeding according to the International Society on Thrombosis and Haemostasis. Results Overall rate of minor bleeds was 19.2 per 100 patient years of follow-up. Bleeding rates for apixaban, dabigatran and rivaroxaban were 26, 8.3 and 23 per 100 patient-years of follow-up. Next to the type of NOAC, the main risk indicators for minor bleedings during NOAC therapy were a HAS-BLED score of 3 or higher and novel anticoagulant use (no history of vitamin K antagonist use). Limitation This was a retrospective observational study evaluating NOAC treatment in a non-randomized setting. Conclusion Our data showed that minor bleeds are common in novel NOAC users, especially when using apixaban and rivaroxaban. In the latter two NOACs, hematoma (bruises) and nose bleeds were more frequently observed and accounted for the difference with dabigatran. Besides type of NOAC, a higher HAS-BLED score and novel anticoagulant drug use were associated with an increased risk of minor bleeding.

Equal-bin-width histogram versus equal-bin-count histogram

The histogram has all its bin widths equal to some non-random number arbitrary set by an analyst (EBWH). In the result, particular bin counts are random variables. This paper presents also a histogram that is constructed in a converse manner. Bin counts are all equal to some non-random number arbitrary set by an analyst (EBCH). In the result, particular bin widths are random variables. The first goal of the paper is a choose of constant bin width (of bin numbers k) in the EBWH, which maximize the similarity measure in the Monte Carlo simulation. The second goal is a choose of constant bin count in the EBCH, which maximize the similarity measure in the Monte Carlo simulation. The third goal is to present similarity measures between empirical and theoretical data. The fourth goal is the comparative analysis of two histogram methods by means of the frequency formula. The first additional goal is a tip how to proceed in EBCH when modulo(n,k)≠0. The second additional goal is the software in the form of a Mathcad file with the implementation of EBWH and EBCH.

Aflatoxin exposure in utero and birth and growth outcomes in Tanzania.

Some evidence suggests that aflatoxin may contribute to the high prevalence of stunting observed in low‐income countries. Whereas several studies have been conducted in West Africa, fewer exist in East Africa and even fewer in nonagricultural contexts. We analyzed serum samples from 400 iron‐replete, nonanemic pregnant women from a cohort in Dar es Salaam, Tanzania to determine the extent and magnitude of exposure to aflatoxin and to study the relationship between levels of aflatoxin exposure in utero and infant birth and growth outcomes. Ninety‐nine percent of women had detectable concentrations of aflatoxin B1‐lysine (AFB1‐lysine), with a median level of 1.4‐pg/mg albumin, indicating a much lower level compared to studies of rural populations in sub‐Saharan Africa. Our results do not show a statistically significant relationship between AFB1‐lysine levels and birth weight, small for gestational age, or prematurity. We observe a small statistically significant reduction in gestational age at delivery (0.47 weeks; 95% CI: −0.86, −0.07) as the natural log of AFB1‐lysine levels increases by 1 unit of pg/mg of albumin, after controlling for potential confounders. Among a nonrandom set of infants who had measurements for placental weight, haemoglobin at delivery, and follow‐up z‐score measurements, we find no association between aflatoxin plasma concentrations and these variables. These findings suggest a high prevalence of chronic low‐level exposure to aflatoxin, though its effect on birth outcomes in this population remains unclear. Our research adds to a growing body of literature finding mixed associations between aflatoxins on pregnancy outcomes and child growth.

Difference-in-Differences as an Alternative to Pretest–Posttest Regression for Social Work Intervention Evaluation and Research

Abstract Nonrandomized evaluation designs are an important part of social work research because randomization is not always feasible in social work settings. Although randomly assigned groups are assumed to be equivalent, nonrandomly assigned groups are not. In nonrandomized settings, designs with multiple waves are ideal, but two-wave designs are still widely used. A common method for estimating a treatment effect in nonrandom two-wave designs is the pretest–posttest model. However, depending on relationships among participants and the method of assignment to treatment groups, researchers should consider a difference-in-differences approach to testing treatment effects. Authors describe and compare the pretest–posttest and difference-in-differences approaches and assumptions and offer guidelines, developed from a literature review, about the conditions under which each model is likely to be best. Authors also demonstrate the decision-making process and application of the methods in an evaluation of an elementary school intervention program.

1966 Structured Teaching to Enhance Laparoscopy Learning

Study Objective To measure the impact of a standardized laparoscopic curriculum on knowledge and simulation skills assessment in Ob/Gyn residents Design Non-Randomized Control Trial Setting Three residency programs in Chicago, IL Patients or Participants Twenty-four residents Interventions A standardized laparoscopic curriculum was developed in accordance with Fundamentals of Laparoscopic Surgery (FLS) training guidelines. The educational program consisted of a didactic lecture with a written pre and post test and laparoscopic simulation training. Residents were trained in peg transfer and precision pattern cutting skills. A skills assessment was administered pre and post simulation training. This skills assessment measured time to completion of peg transfer and time to completion of precision cutting. Data points were assessed using a repeated measures analysis of variance. Measurements and Main Results The residents were evaluated with a significant improvement in knowledge score from 66.7% to 84.4% (p Conclusion Implementing a standardized curriculum improved resident knowledge and simulation skills in laparoscopic techniques. The program demonstrated an improvement in residency learning and could be applied to improve resident training in laparoscopy and FLS training.