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Nevin Manimala Statistics

Automated Plan Checking Software Demonstrates Continuous and Sustained Improvements in Safety and Quality: A 3-year Longitudinal Analysis

Pract Radiat Oncol. 2021 Oct 17:S1879-8500(21)00284-8. doi: 10.1016/j.prro.2021.09.014. Online ahead of print.

ABSTRACT

PURPOSE: Perform a longitudinal analysis of the performance of our automated plan checking software by retrospectively evaluating the number of errors identified in plans delivered to patients in three, month-long, data collection periods taken between 2017 and 2020.

METHODS: 11 automated checks were retrospectively run on 1169 external beam radiotherapy treatment plans identified as meeting the following criteria: planning target volume (PTV) based multi-field photon plans receiving a status of treatment approved in either March 2017, March 2018, or March 2020. The number of “passes” (true positives) and “flags” were recorded. “Flags” were sub-categorized into “false negatives”, “false negatives due to naming conventions”, or “true negatives”. 2 × 2 contingency tables using a two-tailed Fischer’s exact test were utilized to determine whether there were nonrandom associations between the output of the automated plan checking software and whether the check was manual or automated at the original time of treatment approval.

RESULTS: A statistically significant decrease in flags between the pre- and post-automation datasets was observed for four contour-based checks, namely “adjacent structures overlap”, “empty structures and missing slices”, “overlap between body and couch”, and “laterality”, as well as a check that determined whether the plan’s global maximum dose was within the planning target volume. Review of the origins of false negatives was fed back into the design of the checks to improve the reliability of the system and help avoid warning fatigue.

CONCLUSIONS: Periodic and longitudinal review of the performance of automated software is essential for monitoring and understanding its impact on error rates as well as for optimization of the tool to adapt to regular changes of clinical practice. The automated plan checking software has demonstrated continuous contributions to the safe and effective delivery of external beam radiotherapy to our patient population, an impact that extends beyond its initial implementation and deployment.

PMID:34670137 | DOI:10.1016/j.prro.2021.09.014

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Nevin Manimala Statistics

End-of-life use of antibiotics: a survey on how doctors decide

Int J Infect Dis. 2021 Oct 17:S1201-9712(21)00808-0. doi: 10.1016/j.ijid.2021.10.026. Online ahead of print.

ABSTRACT

OBJECTIVES: Infections are the main complications in terminal diseases. Many patients die using antibiotics, which raises questions about their real usefulness and role in unnecessary prolongation of suffering. This survey evaluated how doctors use antibiotics in palliative care.

METHODS: From June to August of 2016, an online survey was conducted with 224 doctors who provide palliative care. They had to decide whether to initiate antibiotics in fictitious scenarios involving patients with suspected infections (urinary tract infection, pneumonia, sepsis) in end-of-life (from cancer, dementia, malignant stroke with sequelae, advanced COPD, multiple organ failure). Then, they had to decide whether to stop, maintain, or extend antibiotics after non-response in 72 hours.

RESULTS: 88-100% of doctors decided to initiate antibiotics in all situations, except in advanced dementia (55%), and most of them decided to maintain/extend antibiotics inadequately. Factors associated with maintaining/extending antibiotics inadequately were: longer time since graduation (over 13 years; significant in all 7 clinical situations; OR range: 2.45-10.11), and not having formal specialization in palliative care (statistically significant in 3 of 7 situations).

CONCLUSIONS: Most palliative care physicians in this study decided to initiate and maintain/extend antibiotics at the end-of-life.

PMID:34670142 | DOI:10.1016/j.ijid.2021.10.026

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Nevin Manimala Statistics

Skin-to-skin contact and deaths in newborns weighing up to 1800 grams: a cohort study

J Pediatr (Rio J). 2021 Oct 17:S0021-7557(21)00134-0. doi: 10.1016/j.jped.2021.09.001. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association between dose of skin-to-skin contact (SSC) per day and initiation time with the occurrence of deaths in newborns with weight up to 1800g.

METHOD: Multicentric cohort in five Brazilian neonatal units, including newborns with a birth weight of ≤1800g. The time of SSC was registered in individual file, by the team or family during the hospitalization. Maternal and newborn data were obtained through questionnaires applied to mothers and in medical records. Classification Tree was used for data analysis.

RESULTS: The performance of the first SSC after 206h was significantly associated with death (p = 0.02). Although there was no association between SSC/day and death (p = 0.09), the number of deaths among those who performed more than 146.9 minutes/day was lower (3;1.5%) than among those who performed this practice for a shorter time (13;6.4%), a fact considered of great clinical importance. Early and late infections present statistically significant associations with the outcome. The chance of death was equal to zero when there was no early infection in the group with the longest duration of SSC. This probability was also equal to zero in the absence of late sepsis for the group with less than 146.9 minutes/day of SSC.

CONCLUSIONS: The first SSC before 206 hours of life is recommended in order to observe a reduction in the risk of neonatal death. Staying in SSC for more than 146.9 min/day seems to be clinically beneficial for these neonates mostly when it was associated with the absence of infection.

PMID:34670115 | DOI:10.1016/j.jped.2021.09.001

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Nevin Manimala Statistics

Ability of the Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT) to Predict Discharge to Institutional Post-Acute Care

Arch Phys Med Rehabil. 2021 Oct 17:S0003-9993(21)01448-9. doi: 10.1016/j.apmr.2021.04.028. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize the ability of the patient-reported Functional Assessment in Acute Care Multidimensional Computerized Adaptive Test (FAMCAT) domains to predict discharge disposition when administered during acute care stays.

DESIGN: Cohort Study. Logistic regression models were estimated to identify the ability of FAMCAT domains to predict discharge to an institution for post-acute care (PAC).

SETTING: Academic Medical Center PARTICIPANTS: Patients admitted to General Medicine Services from June 2016 to June 2019, n = 4,240 INTERVENTIONS: Not applicable.

MAIN OUTCOME MEASURE(S): discharge to an institution RESULTS: In this sample, 10.5% of patients were discharged to an institution for rehabilitation versus home. FAMCAT domain scores were highly predictive of discharge to institutional PAC. Daily Activity and Basic Mobility domains had excellent discriminative ability for discharge to an institution (c-statistic 0.83 and 0.87, respectively). In best fit models accounting for additional characteristics, discrimination was outstanding for Daily Activity (c-statistic 0.91, 95% CI: 0.89, 0.94) and Basic Mobility (c-statistic 0.92, 95% CI: 0.89, 0.94).

CONCLUSION(S): The FAMCAT Daily Activity and Mobility domains demonstrated excellent discrimination for identifying patients who discharged to an institutional setting for rehabilitation, and outstanding discrimination when adjusted for salient patient factors associated with discharge disposition. Estimates obtained in this investigation are comparable to the best discrimination achieved with clinician-rated measures to identify patients who would require institutional PAC.

PMID:34670134 | DOI:10.1016/j.apmr.2021.04.028

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Nevin Manimala Statistics

Multi-year investigation of a relaxation course with a mindfulness meditation component on college students’ stress, resilience, coping and mindfulness

J Am Coll Health. 2021 Oct 20:1-6. doi: 10.1080/07448481.2021.1987918. Online ahead of print.

ABSTRACT

OBJECTIVE: Examine the effects of a relaxation course with a mindfulness meditation component in a two-group pre-test and post-test non-randomized study design.

PARTICIPANTS: Participants included 219 undergraduate students (experimental group: n = 103; control group: n = 116), 18-43 years old.

METHODS: Completion of measures of stress, resilience, coping and mindfulness at the beginning and end of the intervention.

RESULTS: The independent sample t-test analysis revealed a statistically significant decrease in stress and maladaptive coping, and an increase in resilience in the experimental group compared to the control group.

CONCLUSION: Benefits were observed following the intervention by positively impacting factors associated with increased functioning in life. Classroom-based interventions could be considered beneficial for students.

PMID:34670109 | DOI:10.1080/07448481.2021.1987918

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Nevin Manimala Statistics

A novel statistical test for treatment differences in clinical trials using a response adaptive forward looking gittins index rule

Biometrics. 2021 Oct 20. doi: 10.1111/biom.13581. Online ahead of print.

ABSTRACT

The most common objective for response adaptive clinical trials is to seek to ensure that patients within a trial have a high chance of receiving the best treatment available by altering the chance of allocation on the basis of accumulating data. Approaches which yield good patient benefit properties suffer from low power from a frequentist perspective when testing for a treatment difference at the end of the study due to the high imbalance in treatment allocations. In this work we develop an alternative pairwise test for treatment difference on the basis of allocation probabilities of the covariate-adjusted response-adaptive randomization with forward looking Gittins index rule (CARA-FLGI) for binary responses. The performance of the novel test is evaluated in simulations for two-armed studies and then its applications to multi-armed studies is illustrated. The proposed test has markedly improved power over the traditional Fisher exact test when this class of non-myopic response adaptation is used. We also find that the test’s power is close to the power of a Fisher exact test under equal randomization. This article is protected by copyright. All rights reserved.

PMID:34669968 | DOI:10.1111/biom.13581

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Nevin Manimala Statistics

Trans-ethnic Mendelian-randomization study reveals causal relationships between cardiometabolic factors and chronic kidney disease

Int J Epidemiol. 2021 Oct 20:dyab203. doi: 10.1093/ije/dyab203. Online ahead of print.

ABSTRACT

BACKGROUND: This study was to systematically test whether previously reported risk factors for chronic kidney disease (CKD) are causally related to CKD in European and East Asian ancestries using Mendelian randomization.

METHODS: A total of 45 risk factors with genetic data in European ancestry and 17 risk factors in East Asian participants were identified as exposures from PubMed. We defined the CKD by clinical diagnosis or by estimated glomerular filtration rate of <60 ml/min/1.73 m2. Ultimately, 51 672 CKD cases and 958 102 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13 093 CKD cases and 238 118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo were included.

RESULTS: Eight risk factors showed reliable evidence of causal effects on CKD in Europeans, including genetically predicted body mass index (BMI), hypertension, systolic blood pressure, high-density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein(a), type 2 diabetes (T2D) and nephrolithiasis. In East Asians, BMI, T2D and nephrolithiasis showed evidence of causality on CKD. In two independent replication analyses, we observed that increased hypertension risk showed reliable evidence of a causal effect on increasing CKD risk in Europeans but in contrast showed a null effect in East Asians. Although liability to T2D showed consistent effects on CKD, the effects of glycaemic phenotypes on CKD were weak. Non-linear Mendelian randomization indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI of >25 kg/m2.

CONCLUSIONS: Eight cardiometabolic risk factors showed causal effects on CKD in Europeans and three of them showed causality in East Asians, providing insights into the design of future interventions to reduce the burden of CKD.

PMID:34669934 | DOI:10.1093/ije/dyab203

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Nevin Manimala Statistics

webTWAS: a resource for disease candidate susceptibility genes identified by transcriptome-wide association study

Nucleic Acids Res. 2021 Oct 20:gkab957. doi: 10.1093/nar/gkab957. Online ahead of print.

ABSTRACT

The development of transcriptome-wide association studies (TWAS) has enabled researchers to better identify and interpret causal genes in many diseases. However, there are currently no resources providing a comprehensive listing of gene-disease associations discovered by TWAS from published GWAS summary statistics. TWAS analyses are also difficult to conduct due to the complexity of TWAS software pipelines. To address these issues, we introduce a new resource called webTWAS, which integrates a database of the most comprehensive disease GWAS datasets currently available with credible sets of potential causal genes identified by multiple TWAS software packages. Specifically, a total of 235 064 gene-diseases associations for a wide range of human diseases are prioritized from 1298 high-quality downloadable European GWAS summary statistics. Associations are calculated with seven different statistical models based on three popular and representative TWAS software packages. Users can explore associations at the gene or disease level, and easily search for related studies or diseases using the MeSH disease tree. Since the effects of diseases are highly tissue-specific, webTWAS applies tissue-specific enrichment analysis to identify significant tissues. A user-friendly web server is also available to run custom TWAS analyses on user-provided GWAS summary statistics data. webTWAS is freely available at http://www.webtwas.net.

PMID:34669946 | DOI:10.1093/nar/gkab957

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Nevin Manimala Statistics

Use of Machine Learning-Based Software for the Screening of Thyroid Cytopathology Whole Slide Images

Arch Pathol Lab Med. 2021 Oct 20. doi: 10.5858/arpa.2020-0712-OA. Online ahead of print.

ABSTRACT

CONTEXT.—: The use of whole slide images (WSIs) in diagnostic pathology presents special challenges for the cytopathologist. Informative areas on a direct smear from a thyroid fine-needle aspiration biopsy (FNAB) smear may be spread across a large area comprising blood and dead space. Manually navigating through these areas makes screening and evaluation of FNA smears on a digital platform time-consuming and laborious. We designed a machine learning algorithm that can identify regions of interest (ROIs) on thyroid fine-needle aspiration biopsy WSIs.

OBJECTIVE.—: To evaluate the ability of the machine learning algorithm and screening software to identify and screen for a subset of informative ROIs on a thyroid FNA WSI that can be used for final diagnosis.

DESIGN.—: A representative slide from each of 109 consecutive thyroid fine-needle aspiration biopsies was scanned. A cytopathologist reviewed each WSI and recorded a diagnosis. The machine learning algorithm screened and selected a subset of 100 ROIs from each WSI to present as an image gallery to the same cytopathologist after a washout period of 117 days.

RESULTS.—: Concordance between the diagnoses using WSIs and those using the machine learning algorithm-generated ROI image gallery was evaluated using pairwise weighted κ statistics. Almost perfect concordance was seen between the 2 methods with a κ score of 0.924.

CONCLUSIONS.—: Our results show the potential of the screening software as an effective screening tool with the potential to reduce cytopathologist workloads.

PMID:34669924 | DOI:10.5858/arpa.2020-0712-OA

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Nevin Manimala Statistics

The Risk of Later Diagnosis of Inflammatory Bowel Disease in Patients With Dermatological Disorders Associated With Inflammatory Bowel Disease

Inflamm Bowel Dis. 2021 Oct 20;27(11):1731-1739. doi: 10.1093/ibd/izaa344.

ABSTRACT

BACKGROUND: Dermatological conditions such as erythema nodosum (EN), pyoderma gangrenosum, Sweet’s syndrome, and aphthous stomatitis can occur with inflammatory bowel disease (IBD) and are considered dermatological extraintestinal manifestations (D-EIMs). Rarely, they may precede IBD. Other common conditions such as psoriasis have also been associated with IBD. This study examined the risk of a subsequent IBD diagnosis in patients presenting with a D-EIM.

METHODS: A retrospective cohort study compared patients with D-EIMs and age-/sex-matched patients without D-EIMs. Hazard ratios (HRs) were adjusted for age, sex, body mass index, deprivation, comorbidity, smoking, loperamide use, anemia, and lower gastrointestinal symptoms. Logistic regression was used to produce a prediction model for the diagnosis of IBD within 3 years of EN diagnosis.

RESULTS: We matched 7447 patients with D-EIMs (74% female; median age 38 years (interquartile ratio [IQR], 24-65 years) to 29,297 patients without D-EIMs. We observed 131 (1.8%) subsequent IBD diagnoses in patients with D-EIMs compared with 65 (0.2%) in those without D-EIMs. Median time to IBD diagnosis was 205 days (IQR, 44-661 days) in those with D-EIMs and 1594 days (IQR, 693-2841 days) in those without D-EIMs. The adjusted HR for a later diagnosis of IBD was 6.16 (95% confidence interval [CI], 4.53-8.37; P < 0.001), for ulcerative colitis the HR was 3.30 (95% CI, 1.98-5.53; P < 0.001), and for Crohn’s disease the HR was 8.54 (95% CI, 5.74-12.70; P < 0.001). Patients with psoriasis had a 34% increased risk of a subsequent IBD diagnosis compared with the matched control patients (HR, 1.34; 95% CI, 1.20-1.51; P < 0.001). We included 4043 patients with an incident EN diagnosis in the prediction model cohort, with 87 patients (2.2%) diagnosed with IBD within 3 years. The model had a bias-corrected c-statistic of 0.82 (95% CI, 0.78-0.86).

CONCLUSIONS: Patients with D-EIMs have a 6-fold increased risk of a later diagnosis of IBD. Younger age, smoking, low body mass index, anemia, and lower gastrointestinal symptoms were associated with an increased risk of diagnosis of IBD within 3 years in patients with EN.

PMID:34669933 | DOI:10.1093/ibd/izaa344