Nevin Manimala

Psychometrika. 2022 Feb 1. doi: 10.1007/s11336-021-09834-6. Online ahead of print.

ABSTRACT

Equal parameter estimates across subgroups is a substantial requirement of statistical tests. Ignoring subgroup differences poses a threat to study replicability, model specification, and theory development. Structural change tests are a powerful statistical technique to assess parameter invariance. A core element of those tests is the empirical fluctuation process. In the case of parameter invariance, the fluctuation process asymptotically follows a Brownian bridge. This asymptotic assumption further provides the basis for inference. However, the empirical fluctuation process does not follow a Brownian bridge in small samples, and this situation is amplified in large psychometric models. Therefore, common methods of obtaining the sampling distribution are invalid and the structural change test becomes conservative. We discuss an alternative solution to obtaining the sampling distribution-permutation approaches. Permutation approaches estimate the sampling distribution through resampling of the dataset, avoiding distributional assumptions. Hereby, the tests power are improved. We conclude that the permutation alternative is superior to standard asymptotic approximations of the sampling distribution.

PMID:35103931 | DOI:10.1007/s11336-021-09834-6

Geroscience. 2022 Feb 1. doi: 10.1007/s11357-021-00489-w. Online ahead of print.

ABSTRACT

Missing data are ubiquitous in aging studies. Combining the National Health and Nutrition Examination Survey (NHANES) 2003/2004 and 2005/2006 cross-sectional aging studies (N = 9307), we investigated the effects of both real and simulated missing data on the Frailty Index (FI) and survival analysis, along with several mitigation strategies. We observed distinct block patterns of missing variables in the dataset. These blocks showed significant hazard rate (HR) differences when they were missing versus present, indicating that missingness cannot be simply ignored. Simulations of this patterned missingness produced a bias of 0.0112 ± 0.0008 to the mean FI when missing values were ignored, representing a change in hazard of 1.09 ± 0.01. A similar bias of 0.0106 ± 0.0001 was estimated in the real missingness. Imputation was able to correct the bias using the multivariate imputation by chained equations (MICE) method via the classification and regression tree (CART) prediction model together with rule-based imputation. Using auxiliary variables (CART+Aux) improved the performance of CART. Well-performing imputation models, especially CART+Aux, were able to increase the FI predictive power and the reliability of the HR estimates. In contrast, the default MICE models, predictive mean matching/logistic regression (PMM/logreg), caused even stronger biases to the FI. Our results demonstrate that calibration of the FI as a mortality predictor depends on how missing data are handled. Ignoring missing values when calculating the FI may be an acceptable strategy for clinical settings where the FI is used as a rough predictor of adverse outcomes. Where the FI is to be compared across studies or populations, judicious imputation – cognizant of the risks carried by poor imputation – should be used to ensure reliability and precision of statistical estimates and conclusions.

PMID:35103915 | DOI:10.1007/s11357-021-00489-w

J Neurooncol. 2022 Feb 1. doi: 10.1007/s11060-022-03955-3. Online ahead of print.

ABSTRACT

BACKGROUND: MGMT promoter methylation has been associated with favorable prognosis and survival outcomes in patients with glioblastoma and WHO grade III glioma. However, the effects of promoter methylation of MGMT in patients with WHO grade II gliomas have not been established. The purpose of the current study is to evaluate the prognostic impact and predictive values of MGMT methylation in patients with grade II glioma.

METHODS: The National Cancer Database (NCDB) was queried (2004-2016) for patients with newly diagnosed grade II glioma. Demographics and clinical characteristics of these patients were examined. Statistics included Kaplan-Meier overall survival (OS) analysis alongside Cox proportional hazards modeling.

RESULTS: A total of 11,223 patients met the selection criteria; 1252 patients (11%) had MGMT testing. Of the patients who had MGMT testing, 58.5% were MGMT methylated (mMGMT), and 43.5% were MGMT unmethylated (uMGMT). mMGMT patients had greater median overall survival (77.3 months) than both uMGMT patients (42.6 months) and patients with no MGMT status reported (61.9 months (p < 0.001 for both). mMGMT was also associated with improved OS, when compared to patients with uMGMT, for patients receiving adjuvant chemoradiation or adjuvant radiation therapy.

CONCLUSIONS: This is the largest study to date demonstrating both the prognostic and predictive impact of MGMT methylation on patients with grade II glioma. The current results show that mMGMT is a prognostic factor and possibly a predictive biomarker for grade II glioma patients. MGMT methylation status can be used to determine and stratify patients by risk levels, and thus select patients for treatment intensification.

IMPORTANCE OF STUDY: The present study is the largest to date examining the prognostic and predictive significance of MGMT methylation (mMGMT) in patients with WHO grade II glioma. The results suggest that mMGMT is prognostic with increasing overall survival rates for patients with mMGMT compared to uMGMT patients. The results also suggest that mMGMT is predictive as shown by improved overall survival in patients receiving gross total resection, adjuvant chemoradiation or adjuvant radiation therapy, but no difference was observed in patients receiving adjuvant chemotherapy or no adjuvant treatment.

PMID:35103907 | DOI:10.1007/s11060-022-03955-3

Tech Coloproctol. 2022 Feb 1. doi: 10.1007/s10151-022-02582-4. Online ahead of print.

ABSTRACT

BACKGROUND: Surgical management of anal fistulas in Crohn’s disease (CD) is associated with high failure rates, and treatment options are limited due to ongoing proctitis, multiple tracts, and concern for incontinence and non-healing wounds. The aim of this study was to investigate the healing rate of ligation of the inters-sphincteric fistula tract (LIFT) for anal fistulas in Crohn’s disease and identify prognostic factors for healing.

METHODS: This prospective analysis compared long-term healing rates of CD patients undergoing LIFT for anal fistulas. Consecutive patients with CD who underwent LIFT procedure at our institution, in the period from March 2012 to September 2019 were included. The main outcome was anal fistula healing rate.

RESULTS: The study cohort of 46 patients (mean age of 34.2 ± 13.0 years, 18 (40%) males). After a mean follow-up time of 33 ± 28 months, fistula healing was seen in 30 (65%) patients. A total of 8 patients were noted to have inter-sphincteric recurrence and 8 patients had trans-sphincteric recurrence. Smoking at the time of surgery was significantly associated with LIFT failure (HR 3.18, 95% CI 1.18-8.61, p = 0.02). Other factors, such as age, sex, race, disease duration and location, type of fistula history of proctitis, preoperatively use of biologics or a seton, and previous repair attempts, did not appear to influence LIFT healing. Although not statistically significant, there was a trend toward increase in failure among patients with active proctitis at the time of surgery (HR 1.97, 95% CI 0.71-5.42, p = 0.19).

CONCLUSION: Our increasing experience with LIFT for anal fistula in CD demonstrates a higher rate of healing (65%) than previously reported (48%). Smoking appears to negatively influence healing of LIFT in CD.

PMID:35103901 | DOI:10.1007/s10151-022-02582-4

Int J Cardiovasc Imaging. 2022 Feb 1. doi: 10.1007/s10554-022-02541-y. Online ahead of print.

ABSTRACT

Previous reports suggested that poor pulmonary function was associated with increased arterial elastance (Ea) in patients with chronic obstructive pulmonary disease and systemic sclerosis. The mechanisms connecting pulmonary function and Ea have not yet been accurately studied in patients with idiopathic pulmonary fibrosis (IPF). The present study was designed to assess Ea in IPF patients without chronic severe pulmonary hypertension and to determine its prognostic role over a medium-term follow-up. This retrospective study included 60 consecutive patients with mild-to-moderate IPF (73.8 ± 6.6 years, 75% males) and 60 controls matched by age, sex and cardiovascular risk factors. All patients underwent physical examination, spirometry, blood tests, modified Haller index (MHI, chest transverse diameter over the distance between sternum and spine) assessment, conventional transthoracic echocardiography implemented with speckle tracking analysis of left atrial positive global strain (LA-GSA+ ) and finally carotid Doppler ultrasonography, at basal evaluation. The effective arterial elastance index (EaI) was calculated as the ratio of end-systolic pressure to stroke volume index. During follow-up period, we evaluated the composite endpoint of (1) pulmonary or cardiovascular hospitalizations; (2) all-cause mortality. At baseline, EaI was significantly higher in IPF patients than controls (4.1 ± 1.3 vs 3.5 ± 1.0 mmHg/ml/m², p = 0.01). EaI was strongly correlated to the following variables: C-reactive protein (CRP) (r = 0.86), forced vital capacity (FVC) (r = – 0.91), E/e’ ratio (r = 0.91), LA-GSA+ (r = – 0.92), common carotid artery-cross sectional area (CCA-CSA) (r = 0.89) and MHI (r = 0.86), in IPF patients. Mean follow-up time was 2.4 ± 1.3 years. During follow-up, 12 patients died and 17 were hospitalized due to major adverse clinical events. At univariate Cox analysis, CRP (HR 1.51, 95% CI 1.25-1.82), FVC (HR 0.88, 95% CI 0.85-0.91), LA-GSA+ (HR 0.85, 95% CI 0.77-0.94), CCA-CSA (HR 1.12, 95% CI 1.03-1.22) and EaI (HR 2.43, 95% CI 1.75-3.37) were significantly associated with outcome. At multivariate Cox analysis, only EaI (HR 1.60, 95% CI 1.03-2.50) retained statistical significance. An EaI ≥ 4 mmHg/ml/m² showed 100% sensitivity and 99.4% specificity for predicting outcome (AUC = 0.98). In patients with mild-to-moderate IPF, an EaI ≥ 4 mmHg/ml/m² is a negative prognostic factor over a medium-term follow-up.

PMID:35103898 | DOI:10.1007/s10554-022-02541-y

Biodegradation. 2022 Feb 1. doi: 10.1007/s10532-022-09972-3. Online ahead of print.

ABSTRACT

The present study is aimed to develop a microbial system for efficient naphthalene bioremediation. A phytotoxicity study was carried out to check the naphthalene detoxification efficiency of Pseudomonas sp. strain SA3 in mung bean (Vigna radiata). For this, administration of the degraded product (supernatant) of 500 mg L^-1 naphthalene by Pseudomonas sp. strain SA3 was studied on V. radiata till 168 h. The growth parameters of mung bean seedlings exposed to treated naphthalene solution were statistically similar to distilled water but a twofold decrease when exposed to untreated naphthalene solution. Further, through the soil microcosm study, the naphthalene degradation by pure colonies of Pseudomonas sp. strain SA3 was 6.8% higher as compared to when the natural microflora was mixed with Pseudomonas sp. strain SA3. Further naphthalene degradation by a microcosm model revealed that with an increased concentration of glucose, the carbon dioxide trap rate decreases.

PMID:35103887 | DOI:10.1007/s10532-022-09972-3

Health Care Manag Sci. 2022 Feb 1. doi: 10.1007/s10729-021-09589-7. Online ahead of print.

ABSTRACT

Measuring the relative efficiency of a finite fixed set of service-producing units (hospitals, state services, libraries, banks,…) is an important purpose of Data Envelopment Analysis (DEA). We illustrate an innovative way to measure this efficiency using stochastic indexes of the quality from these services. The indexes obtained from the opinion-satisfaction of the customers are estimators, from the statistical view point, of the quality of the service received (outputs); while, the quality of the offered service is estimated with opinion-satisfaction indexes of service providers (inputs). The estimation of these indicators is only possible by asking a customer and provider sample, in each service, through surveys. The technical efficiency score, obtained using the classic DEA models and estimated quality indicators, is an estimator of the unknown population efficiency that would be obtained if in each one of the services, interviews from all their customers and all their providers were available. With the object of achieving the best precision in the estimate, we propose results to determine the sample size of customers and providers needed so that with their answers can achieve a fixed accuracy in the estimation of the population efficiency of these service-producing units through the use of a novel one bootstrap confidence interval. Using this bootstrap methodology and quality opinion indexes obtained from two surveys, one of doctors and another of patients, we analyze the efficiency in the health care system of Spain.

PMID:35103882 | DOI:10.1007/s10729-021-09589-7

Lung. 2022 Feb 1. doi: 10.1007/s00408-022-00513-6. Online ahead of print.

ABSTRACT

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is an accepted alternative to surgical lung biopsy (SLB) for diagnosing diffuse parenchymal lung disease (DPLD) that is less invasive and results in comparable diagnostic yields. Performing lung biopsies on hospitalized patients, however, has increased risk due to the patient’s underlying disease severity. Data evaluating the safety and efficacy of TBLC in hospitalized patients are limited. We present a comparison of TBLC for hospitalized and outpatients and provide the safety and diagnostic yields in these populations.

METHODS: Demographic data, pulmonary function values, chest imaging pattern, procedural information, and diagnosis were recorded from enrolled patients. Complications from the procedure were the primary outcomes and diagnostic yield was the secondary outcome.

RESULTS: 77 patients (n = 22 hospitalized vs n = 55 outpatient) underwent TBLC during the study period. Comparing adverse events between hospitalized and outpatients revealed no statistically significant differences in pneumothorax (9%, n = 2 vs 5%,n = 3), tube thoracostomy placement (5%, n = 1 vs 2%, n = 1), grade 2 bleeding (9%, n = 2 vs 0%, n = 0), escalation in level of care (5%, n = 1 vs 0%, n = 0), 30-day mortality (9%, n = 2 vs 2%, n = 1), and 60-day mortality (9%, n = 2 vs 4%, n = 2) (p > 0.05 for all). No deaths were attributed to the procedure. 95% of cases received a multidisciplinary conference diagnosis (hospitalized 100%, n = 22 vs outpatients 93%, n = 51, p = 0.32).

CONCLUSION: Our experience supports that TBLC may be a safe and effective modality for acutely ill-hospitalized patients with DPLD. Further efforts to enhance procedural safety and to determine the impact of an expedited tissue diagnosis on patient outcomes are needed.

PMID:35103841 | DOI:10.1007/s00408-022-00513-6

JAMA Netw Open. 2022 Feb 1;5(2):e2144959. doi: 10.1001/jamanetworkopen.2021.44959.

ABSTRACT

IMPORTANCE: Little is known about the contribution of hospital antibiotic prescribing to multidrug-resistant organism (MDRO) burden in nursing homes (NHs).

OBJECTIVES: To characterize antibiotic exposures across the NH patient’s health care continuum (preceding health care exposure and NH stay) and to investigate whether recent antibiotic exposure is associated with MDRO colonization and room environment contamination at NH study enrollment.

DESIGN, SETTING, AND PARTICIPANTS: This is a secondary analysis of a prospective cohort study (conducted from 2013-2016) that enrolled NH patients and followed them up for as long as 6 months. The study was conducted in 6 NHs in Michigan among NH patients who were enrolled within 14 days of admission. Clinical metadata abstraction, multi-anatomical site screening, and room environment surveillance for MDROs were conducted at each study visit. Data were analyzed between May 2019 and November 2021.

EXPOSURES: Antibiotic data were abstracted from NH electronic medical records by trained research staff and characterized by class, route, indication, location of therapy initiation, risk for Clostridioides difficile infection (C diffogenic agents), and 2019 World Health Organization Access, Watch, and Reserve (AWARE) antibiotic stewardship framework categories.

MAIN OUTCOMES AND MEASURES: The primary outcomes were MDRO colonization and MDRO room environment contamination at NH study enrollment, measured using standard microbiology methods. Multivariable logistic regression was used to identify whether antibiotic exposure within 60 days was associated with MDRO burden at NH study enrollment. Additionally, antibiotic exposure data were characterized using descriptive statistics.

RESULTS: A total of 642 patients were included (mean [SD] age, 74.7 [12.2] years; 369 [57.5%] women; 402 [62.6%] White; median [IQR] NH days to enrollment, 6.0 [3.0-7.0]). Of these, 422 (65.7%) received 1191 antibiotic exposures: 368 (57.3%) received 971 hospital-associated prescriptions, and 119 (18.5%) received 198 NH-associated prescriptions. Overall, 283 patients (44.1%) received at least 1 C diffogenic agent, and 322 (50.2%) received at least 1 high-risk WHO AWARE antibiotic (watch or reserve agent). More than half of NH patients (364 [56.7%]) and room environments (437 [68.1%]) had MDRO-positive results at enrollment. In multivariable analysis, recent antibiotic exposure was positively associated with baseline MDRO colonization (odds ratio [OR], 1.70; 95% CI, 1.22-2.38) and MDRO environmental contamination (OR, 1.67; 95% CI, 1.17-2.39). Exploratory stratification by C diffogenic agent exposure increased the effect size (MDRO colonization: OR, 1.99; 95% CI, 1.33-2.96; MDRO environmental contamination: OR, 1.86; 95% CI, 1.24-2.79). Likewise, exploratory stratification by exposure to high-risk WHO AWARE antibiotics increased the effect size (MDRO colonization: OR, 2.32; 95% CI, 1.61-3.36; MDRO environmental contamination: OR, 1.86; 95% CI, 1.26-2.75).

CONCLUSIONS AND RELEVANCE: The findings of this study suggest that high-risk, hospital-based antibiotics are a potentially high-value target to reduce MDROs in postacute care NHs. This study underscores the potential utility of integrated hospital and NH stewardship programming on regional MDRO epidemiology.

PMID:35103795 | DOI:10.1001/jamanetworkopen.2021.44959

JAMA Netw Open. 2022 Feb 1;5(2):e2146026. doi: 10.1001/jamanetworkopen.2021.46026.

ABSTRACT

IMPORTANCE: Current international normalized ratio (INR) guidelines are based on trials involving European and US populations. To our knowledge, no adequate study involving Asian patients has been conducted to date.

OBJECTIVE: To evaluate the association between INR and anticoagulation-related outcomes in an Asian population after mechanical aortic valve replacement (AVR) or mitral VR (MVR).

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted between 2001 and 2018, with follow-up until December 31, 2018, among patients who underwent AVR, MVR, or combined AVR-MVR at 3 medical centers and 4 regional hospitals and contributed electronic medical records to the Chang Gung Research Database. Exclusion criteria were missing demographic characteristics, younger than 20 years, fewer than 2 INR records, and having died during the hospitalization of the index surgery.

MAIN OUTCOMES AND MEASURES: Bleeding and thromboembolic complications were analyzed. The possibility of nonlinearity and cutoff potential for the INR were explored using a logistic regression model, which considered the INR a restricted cubic spline (RCS) variable.

RESULTS: The study population consisted of 900 patients, with 525 (58.3%) men and 375 (41.7%) women and a mean (SD) age of 52.0 (12.5) years. Overall, 474 (52.7%) received AVR alone, 329 (36.6%) received MVR alone, and 97 (10.8%) received combined AVR-MVR. All patients had at least 2 INR examinations after discharge, providing 16 676 INR records for the AVR group and 18 207 for the MVR and combined AVR-MVR groups. In the AVR group, the RCS model showed that higher risks of composite thromboembolic events were associated with an INR of less than 2.0 or greater than 2.6 vs an INR of 2.0, and a higher risk of bleeding events was associated with an INR of less than 1.8 or greater than 2.4 vs an INR of 2.0. When treating the INR as a categorical variable, the risk of composite thromboembolic and composite bleeding events was significantly higher among patients with INRs less than 1.5 (adjusted odds ratio [aOR], 2.55; 95% CI, 1.37-4.73) and with INRs of 3.0 or greater (aOR, 3.48; 95% CI, 1.95-6.23) vs those with INRs between 2.0 and 2.5.In the MVR and combined AVR-MVR groups, higher risks of composite thromboembolic events were associated with an INR of less than 2.1 or greater than 2.7 vs an INR of 2.5, and a higher risk of bleeding events was associated with an INR of less than 2.1 or greater than 2.8 vs an INR of 2.5. When treating the INR as a categorical variable, the risk of a composite bleeding events was significantly higher among patients with INRs of 3.5 or greater (aOR, 2.25; 95% CI, 1.35-3.76) vs those with INRs between 2.5 and 3.0.

CONCLUSIONS AND RELEVANCE: Among Asian patients in this study, the incidence of thromboembolic events in the MVR group with INRs in the range of 2.0 to 2.5 was not significantly higher than that among those with INRs in the range of 2.5 to 3.0; in the AVR group, the incidence for those with INRs in 1.5 to 2.0 range was not significantly higher than for those with INRs in the range of 2.0 to 2.5.

PMID:35103794 | DOI:10.1001/jamanetworkopen.2021.46026