Category: Statistics

Stat Med. 2022 Jan 21. doi: 10.1002/sim.9315. Online ahead of print.

ABSTRACT

Multiple imputation is a promising approach to handle missing data and is widely used in analysis of longitudinal clinical studies. A key consideration in the implementation of multiple imputation is to obtain accurate imputed values by specifying an imputation model that incorporates auxiliary variables potentially associated with missing variables. The use of informative auxiliary variables is known to be beneficial to make the missing at random assumption more plausible and help to reduce uncertainty of the imputations; however, it is not straightforward to pre-specify them in many cases. We propose a data-driven specification of the imputation model using Bayesian lasso in the context of longitudinal clinical study, and develop a built-in function of the Bayesian lasso imputation model which is performed within the framework of multiple imputation using chained equations. A simulation study suggested that the Bayesian lasso imputation model worked well in a variety of longitudinal study settings, providing unbiased treatment effect estimates with well-controlled type I error rates and coverage probabilities of the confidence interval; in contrast, ignorance of the informative auxiliary variables led to serious bias and inflation of type I error rate. Moreover, the Bayesian lasso imputation model offered higher statistical powers compared with conventional imputation methods. In our simulation study, the gains in statistical power were remarkable when the sample size was small relative to the number of auxiliary variables. An illustration through a real example also suggested that the Bayesian lasso imputation model could give smaller standard errors of the treatment effect estimate.

PMID:35064581 | DOI:10.1002/sim.9315

Eur Geriatr Med. 2022 Jan 22. doi: 10.1007/s41999-021-00600-6. Online ahead of print.

ABSTRACT

PURPOSE: To describe the impact of COVID-19 on hip fracture care during the first 6 months of the pandemic.

METHODS: A secondary analysis of 4385 cases in the Irish Hip Fracture Database from 1st June 2019 to 31st August 2020 was conducted.

RESULTS: Hip fracture admissions decreased by 15% during the study period (p < 0.001). Patient characteristics were largely unchanged as the majority of cases occurred in females over 80 years admitted from home. Adherence to many of the Irish Hip Fracture Standards (IHFS) changed following the COVID-19 pandemic. There was an increase in patients admitted to an orthopaedic ward from Emergency Department (ED) within 4 h from 27 to 36% (p < 0.001). However, the proportion of patients reviewed by a geriatrician reduced from 85% pre-COVID to 80% (p < 0.001). Fewer patients received a bone health assessment [90% from 95% (p < 0.001)] and specialist falls assessment [(82% from 88% (p < 0.001)]. No change was seen in time to surgery or incidence of pressure injuries. There was a significant decrease in length of stay from 18 to 14 days (p < 0.001). There was an increase in patients discharged home during the COVID-19 period and a decrease in patients discharged to rehabilitation, convalescence or nursing home care. There was no statistically significant change in mortality.

CONCLUSION: Healthcare services were widely restructured during the pandemic, which had implications for hip fracture patients. There was a notable change in compliance with the IHFS. Multidisciplinary teams involved in hip fracture care should be preserved throughout any subsequent waves of the pandemic.

PMID:35064562 | DOI:10.1007/s41999-021-00600-6

J Am Geriatr Soc. 2022 Jan 22. doi: 10.1111/jgs.17667. Online ahead of print.

ABSTRACT

BACKGROUND: Identifying patients at high risk of drug-related hospital admission (DRA) may help to efficiently target preventive interventions. We developed a score to predict DRAs in older patients with multimorbidity and polypharmacy.

METHODS: We used participants from the multicenter European OPERAM trial (“Optimising PharmacothERapy in the Mutlimorbid Elderly”). We assessed the association between easily identifiable predictors and 1-year DRAs by univariable logistic regression. Variables with p-value< 0.20 were taken forward to backward regression. We retained all variables with p < 0.05 in the model. We assessed the C-statistic, calibration (observed/predicted proportions), and overall accuracy (scaled Brier score, <0.25 indicating a useful model) of the score, and internally validated it by tenfold cross-validation.

RESULTS: Within 1 year, 435/1879 (23.2%) patients (mean age 79.4 years) had a DRA. The score included seven variables: previous hospitalizations, non-elective admission, hypertension, cirrhosis with portal hypertension, chronic kidney disease, diuretic, oral corticosteroid. The C-statistic was 0.64 (95% CI 0.61-0.67). Patients with <1 point had a 12.4% predicted and observed risk of DRA, while those with >3 points had a 40.4% predicted and 38.9% observed risk of DRA. The scaled Brier score was 0.05. Calibration showed an adequate match between predicted and observed proportions.

CONCLUSION: Comorbidities related to drug metabolism, specific medications, non-elective admission, and a history of hospitalization, were associated with a higher risk of DRA. Awareness of these associations and the score we developed may help identify patients most likely to benefit from preventive interventions.

PMID:35064571 | DOI:10.1111/jgs.17667

Acad Psychiatry. 2022 Jan 22. doi: 10.1007/s40596-021-01574-0. Online ahead of print.

ABSTRACT

OBJECTIVE: The relationship between a resident physician and his/her supervising attending is foundational to graduate medical education and may impact the clinical learning environment and resident well-being. This paper focuses on how to measure connection between a resident and their clinical supervisor. Connection includes the subdomains of psychological safety, empathy, educational alliance, and feedback.

METHODS: After reviewing the literature, the authors designed the 12-item, 7-point Connection Index (CI₁₂) to quantitatively measure connections between a resident and his/her supervisor during a 6-month period (supervision dyad), and based on educational alliance, empathy, psychological safety, and effective feedback. A 9-criteria evaluation framework was applied to assess its reliability and validity on a sample of psychiatry residents at a residency program, July 2016 through June 2018.

RESULTS: Out of a total possible number of 50 residents, 100% participated to rate 41 supervisors over 201 supervision dyads; the CI₁₂ satisfied all eight of the eight testable criteria, including high scalability (H = 0.78), consistency (alpha = 0.98), test-retest validity (ICC = 0.95), and construct validity where CI₁₂ was found to have statistically significant correlations with outcomes measures (greater connection was associated with less negative emotional experiences, less mistreatment or bias, less burnout, and higher attendance to supervision sessions).

CONCLUSION: The authors showed the CI₁₂ can be a valid and reliable instrument to quantify whether a resident and his/her supervisor connects during a 6-month supervision with respect to empathy, psychological safety, educational alliance, and feedback. We recommend assessing connections as part of the overall evaluation of a resident’s experience with the clinical learning environment.

PMID:35064549 | DOI:10.1007/s40596-021-01574-0

Ther Innov Regul Sci. 2022 Jan 22. doi: 10.1007/s43441-021-00353-1. Online ahead of print.

ABSTRACT

BACKGROUND: Meta-analysis of related trials can provide an overall measure of safety-signal accounting for variability across studies. In addition to an overall measure, researchers may often be interested in study-specific measures to assess safety of the product. Likelihood ratio tests (LRT) methods serve this purpose by identifying studies that appear to show a safety concern. In this paper, we present a Bayesian approach. Despite having good statistical properties, the LRT methods may not be suitable for the meta-analysis of randomized controlled trials (RCTs) when there are several studies with zero events in at least one arm.

METHODS: In this article, we describe a Bayesian framework using a Zero-inflated binomial model with spike-and-slab parameterization for the treatment effects. In addition to providing an overall meta-analytic estimate, this method provides posterior probability of a safety-signal for each study.

RESULTS: We illustrate the approach using two published data sets comprising several randomized controlled trials (RCTs) each and compare the model performance for different choices of priors for treatment effect.

DISCUSSION: The proposed Bayesian methodological framework is useful to identify potential signal for single adverse event and to determine overall meta-analytic estimate of the magnitude of the signal. Practitioners may consider this approach as an alternative to the frequentist’s LRT approach discussed in Jung et al. (J Biopharm Stat 31:47-54, 2020) when there are zero events in either the treatment arm or the control arm. In the future, this approach can be further extended to accommodate multiple adverse events.

PMID:35064554 | DOI:10.1007/s43441-021-00353-1

Mol Neurobiol. 2022 Jan 22. doi: 10.1007/s12035-021-02685-3. Online ahead of print.

ABSTRACT

Chemotherapy-induced peripheral neuropathy (CIPN) is a serious complication leading to painful episodes of parasthesia and numbness in hands and feet. The present drugs that have been used for symptomatic treatment yield inconclusive results in trials and assorted side effects. Thus, there is a pressing demand for development of therapeutically efficacious strategy to combat CIPN. The present study investigates about the effect of a marine sponge; Cliothosa aurivilli (CA) on paclitaxel (PT)-induced peripheral neuropathy in mice. Peripheral neuropathy was induced by intoxication with chemotherapeutic drug PT (2 mg/kg; i.p.) for 5 days consequently. Subsequent treatment with aqueous extract of CA (100 and 200 mg/kg) and standard drug methylcobalamin (MCA) (5 mg/kg) was done and results compared statistically. Neuropathic pain sensations were assessed using various behavioural and locomotory models and evaluated on 0^th, 7^th and 14^th days. Kinovea software was used for video path-tracking of animals and total distance travelled calculated. The results indicated clear signs of improvement post 10 days of PT intoxication in CA-treated groups when compared PT challenged group. A significant reduction in pain behaviours in mechanical allodynia, cold chemical allodynia and thermal hyperalgesia models, improvement in sensory motor coordination, locomotor activity, and distance travelled in closed field model reveals that CA possesses potential ameliorating effect against PT-induced neuropathic pain symptoms. The extract notably improved the movement of the PT challenged animals which was shown by the video path-tracking software and total distance travelled by those animals.

PMID:35064539 | DOI:10.1007/s12035-021-02685-3

J Gastrointest Cancer. 2022 Jan 22. doi: 10.1007/s12029-021-00775-y. Online ahead of print.

ABSTRACT

BACKGROUND: Despite its declining incidence, gastric cancer (GC) is one of the world’s leading malignancies and a major global health concern due to its high prevalence and fatality rate. Furthermore, it is the world’s fourth most common cancer and the second leading cause of cancer death. Studying the determinants of time to death of gastric cancer patients will give clinicians more information to develop specific treatment plans, forecast prognosis, and track the progress of death cases. The application of the frailty model can help account for random variation in survival that may exist due to unobserved factors, as well as show the impact of latent factors on death risk. As a result, the purpose of this study was to assess the determinants of time to death of GC patients’ by applying the parametric shared frailty models.

METHODS: The data for this study were obtained from gastric cancer patients admitted to the Tikur Anbesa Specialized Hospital, Addis Ababa, from January 1, 2015, to February 29, 2020. With the aim of coming up with an appropriate survival model that determines factors that affect the time to death of gastric cancer patients, various parametric shared frailty models were compared. In all of the frailty models, patient regions were used as a clustering variable. The current study implemented exponential, Weibull, log-logistic, and lognormal distributions for baseline hazard functions with gamma and inverse Gaussian’s frailty distributions. The performance of all models was compared using the AIC and BIC criteria. R statistical software was used to conduct the analysis.

RESULTS: A retrospective study was undertaken on a total of 407 gastric cancer patients under follow-up at Tikur Anbesa Specialized Hospital. Of all 407 GC patients, 56.3% died while the remaining 43.7% were censored. The patients’ median time to death was 21.9 months, with a maximum survival time of 49.6 months. In the current study, the clustering effect was significant in modeling the time to death from gastric cancer. The Weibull model with inverse Gaussian frailty has the minimum AIC and BIC value among the candidate models compared. The dependency within the clusters for the Weibull-inverse Gaussian frailty model was [Formula: see text] (13.4%). According to the results of our best model (Weibull-inverse Gaussian), the sex of the patient, the smoking status, the tumor size, the treatment taken, the vascular invasion, and the disease stage was found to be statistically significant at an alpha = 0.05 significance level.

CONCLUSION: Time to death of GC patient’s data set was well described by the Weibull-inverse Gaussian shared frailty. Furthermore, Weibull baseline distribution best fits the GC data set as it enables proportional hazard and accelerated failure time model, for time to failure data. There is unobserved heterogeneity between clusters (patient regions), indicating the need to account for this clustering effect. In this study, survival time to death among GC patients was discovered to be small. Covariates like older age, being male, having higher (advanced) stage of GC disease (stage three and stage four), advanced tumor size, being smoker, infected by Helicobacter pylori, and existence of vascular invasion significantly accelerate the time to death of GC patients. In contrast, talking combination of more treatments prolongs the time to death of patients. To improve the health of patients, interventions should be taken based on significant prognostic factors, with special attention dedicated to patients with such factors to prevent GC death.

PMID:35064523 | DOI:10.1007/s12029-021-00775-y

Ir J Med Sci. 2022 Jan 22. doi: 10.1007/s11845-022-02920-3. Online ahead of print.

ABSTRACT

Ureteric stents play an essential role in urology. However, patients can suffer a range of stent-related symptoms with stent in situ and during removal. Conventional ureteric stents are removed using a flexible cystoscopy, whereas magnetic stents may be rapidly removed with a smaller catheter-like retrieval device. The primary aim of this systematic review was to compare the morbidity including pain associated with conventional versus magnetic ureteric stents. The secondary aim was cost comparison. Searches were performed across databases, including Medline, Scopus, Embase and Cochrane. This review was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The search from the 5 databases returned a total of 358 articles. After duplicates were removed as well as the inclusion and exclusion criteria applied, a total of 6 studies were included in the final review. Ureteric Stent Symptoms Questionnaire (USSQ) and Visual Analogue Score (VAS) were used in most of the studies. All the studies reported that magnetic ureteric stents resulted in a reduction in the pain on the removal of magnetic ureteric stents, and no statistically significant difference with indwelling ureteric stents. Furthermore, majority of the studies reported a reduction in the cost associated with magnetic ureteric stents. There is no significant difference in pain from indwelling ureteric stents. There is a reduction in pain with the removal of magnetic ureteric stents compared to conventional removal via cystoscopy and an associated reduction in cost.

PMID:35064536 | DOI:10.1007/s11845-022-02920-3

Environ Sci Pollut Res Int. 2022 Jan 21. doi: 10.1007/s11356-022-18696-z. Online ahead of print.

ABSTRACT

Municipal solid waste (MSW) is a highly heterogeneous porous medium that contains a variety of components and has complex pores and solid structures. Macroscale experiments are insufficient to describe the hydraulic and mechanical properties of MSW, especially for preferential flow in pores and the reinforcing effect of solids. For a deep understanding of the microscale structure of MSW, CT scanning tests were carried out on two kinds of samples prepared in the laboratory and drilled in landfills. MSW images were divided into pores and solids through dynamic threshold segmentation and morphological denoising methods. The distributions of pore size and structural solid angle were calculated by the maximum inscribed sphere (MIS) algorithm and angle statistical algorithm based on the surface model, respectively. According to the pore-size distribution, the pores were divided into large (diameter > 1 mm), medium (1 mm > diameter > 0.1 mm), and small (diameter < 0.1 mm) pores in MSW. Under a vertical stress of 50 kPa, the porosities of the large, medium, and small pores were 35%, 12%, and 26%, respectively. As the vertical stress increased to 400 kPa, the porosity of large pores decreased significantly to 15%, while the porosities of medium and small pores remained almost unchanged. In addition, the structural solid angle tended to be horizontal under compression, but its influence was limited. The structural solid angle was mainly concentrated at approximately 30-32°. The probability distribution of the structural solid angle could be well fitted using the Gauss function.

PMID:35064512 | DOI:10.1007/s11356-022-18696-z

J Racial Ethn Health Disparities. 2022 Jan 21. doi: 10.1007/s40615-022-01228-3. Online ahead of print.

ABSTRACT

AIM: This study quantified and compared demographic and clinical features of bipolar disorder (BD) in persons of African ancestry (AA) and European ancestry (EUR).

METHODS: Participants enrolled in the Mayo Clinic Bipolar Biobank from 2009 to 2015. The structured clinical interview for DSM-IV was used to confirm the diagnosis of BD, and a questionnaire was developed to collect data on the clinical course of illness. Descriptive statistics and bivariate analyses were completed to compare AA versus EUR participants. Subsequently, clinical outcomes were compared between AA and EUR participants using linear regression for continuous outcomes or logistic regression for binary outcomes while controlling for differences in age, sex, and recruitment site.

RESULTS: Of 1865 participants enrolled in the bipolar biobank, 65 (3.5%) self-identified as AA. The clinical phenotype for AA participants, in comparison to EUR participants, was more likely to include a history of PTSD (39.7% vs. 26.2%), cocaine use disorder (24.2% vs. 11.9%), and tardive dyskinesia (7.1% vs. 3%).

CONCLUSION: The low rate of AA enrollment is consistent with other genetic studies. While clinical features of bipolar disorder are largely similar, this study identified differences in rates of trauma, substance use, and tardive dyskinesia that may represent health disparities in bipolar patients of African ancestry. Future bipolar biomarker studies with larger sample sizes focused on underrepresented populations will provide greater ancestry diversity in genomic medicine with greater applicability to diverse patient populations, serving to inform health care policies to address disparities in bipolar disorder.

PMID:35064520 | DOI:10.1007/s40615-022-01228-3