Category: Statistics

Int J Rheum Dis. 2021 Aug 12. doi: 10.1111/1756-185X.14203. Online ahead of print.

ABSTRACT

Missing data in clinical epidemiological research violate the intention-to-treat principle, reduce the power of statistical analysis, and can introduce bias if the cause of missing data is related to a patient’s response to treatment. Multiple imputation provides a solution to predict the values of missing data. The main objective of this study is to estimate and impute missing values in patient records. The data from the Kuwait Registry for Rheumatic Diseases was used to deal with missing values among patient records. A number of methods were implemented to deal with missing data; however, choosing the best imputation method was judged by the lowest root mean square error (RMSE). Among 1735 rheumatoid arthritis patients, we found missing values vary from 5% to 65.5% of the total observations. The results show that sequential random forest method can estimate these missing values with a high level of accuracy. The RMSE varied between 2.5 and 5.0. missForest had the lowest imputation error for both continuous and categorical variables under each missing data rate (10%, 20%, and 30%) and had the smallest prediction error difference when the models used the imputed laboratory values.

PMID:34382756 | DOI:10.1111/1756-185X.14203

J Vet Intern Med. 2021 Aug 12. doi: 10.1111/jvim.16238. Online ahead of print.

ABSTRACT

BACKGROUND: Rates of detecting ≥1 potential enteric pathogens (PEP) or toxins (PEP-T) in feces, blood, or both of horses ≥6 months of age with enteric disease and impact of multiple detections on outcome of horses with colitis has not been reported.

OBJECTIVE: To determine detection rates of PEP/PEP-T in feces, blood, or both of horses with enteric disease and effect of detecting multiple agents on outcome of horses with colitis.

ANIMALS: Thirty-seven hundred fifty-three fecal samples submitted to IDEXX Laboratories and 239 fecal and blood samples submitted to Michigan State University’s Veterinary Diagnostic Laboratory (MSUVDL).

METHODS: Retrospective evaluation of PEP/PEP-T testing results was performed to determine rates of detection of 1 or more PEP/PEP-T. Impact of detecting multiple agents on outcome was assessed in 239 horses hospitalized for colitis.

RESULTS: One or more PEP/PEP-T was detected in 1175/3753 (31.3%) and 145/239 (60.7%) of samples submitted to IDEXX Laboratories and MSUVDL, respectively. In a hospitalized cohort, survival to discharge was lower (76%) in horses with 1 agent, compared to horses with either no (88%) or multiple (89%) agents. There was no difference (P = .78) in days of hospitalization between horses with 0 (1-17), 1 (1-33), and > 1 positive (1-20) result. There was no difference in cost of hospitalization (P = .25) between horses with 0 ($2357, $1110-15 553), 1 ($2742, $788-11 005), and >1 positive ($2560, $1091-10 895) result.

CONCLUSIONS AND CLINICAL IMPORTANCE: Detection rates of PEP/PEP-T in horses with colitis vary with cohorts and tests performed. Detection of more than 1 PEP or PEP-T did not affect outcome.

PMID:34382708 | DOI:10.1111/jvim.16238

J Magn Reson Imaging. 2021 Aug 12. doi: 10.1002/jmri.27884. Online ahead of print.

ABSTRACT

BACKGROUND: Some patients with type 2 diabetes mellitus (T2DM) progress towards mild cognitive impairment (MCI), while some patients can always maintain normal cognitive function. Network topologic alterations at global and nodal levels between T2DM individuals with and without cognitive impairment may underlie the difference.

PURPOSE: To investigate the topological alterations of the whole-brain white matter (WM) structural connectome in T2DM patients with and without MCI and characterize its relationship with disease severity.

STUDY TYPE: Cross-sectional and prospective study.

SUBJECTS: Forty-four (63.6% females) T2DM patients, 22 with mild cognitive impairment (DM-MCI) and 22 with normal cognition (DM-NC), and 34 (58.8% females) healthy controls (HC).

FIELD STRENGTH/SEQUENCE: 3 T/diffusion tensor imaging.

ASSESSMENT: Graph theoretical analysis was used to investigate the topological organization of the structural networks. The global topological properties and nodal efficiency were investigated and compared. Relationship between network metrics and clinical measurements was characterized.

STATISTICAL TESTS: Student’s t-test, chi-square test, ANOVA, partial correlation analyses, and multiple comparisons correction.

RESULTS: The global topological organization of WM networks was significantly disrupted in T2DM patients with cognitive impairment (reduced global and local efficiency and increased shortest path length) but not in those with normal cognition, compared with controls. The DM-MCI group had significantly decreased network efficiency compared with the DM-NC group. Compared with controls, decreased nodal efficiency was detected in three regions in DM-NC group. More regions with decreased nodal efficiency were found in the DM-MCI group. Altered global network properties and nodal efficiency of some regions were correlated with diabetic duration, HbA1c levels, and cognitive assessment scores.

DATA CONCLUSION: The more disrupted WM connections and weaker organized network are found in DM-MCI patients relative to DM-NC patients and controls. Network analyses provide information for the neuropathology of cognitive decline in T2DM patients. Altered nodal efficiency may act as potential markers for early detection of T2DM-related MCI.

LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 2.

PMID:34382716 | DOI:10.1002/jmri.27884

Neurosurgery. 2021 Aug 12:nyab295. doi: 10.1093/neuros/nyab295. Online ahead of print.

ABSTRACT

BACKGROUND: Conflicting evidence exists regarding the effectiveness of surgery for degenerative cervical myelopathy (DCM), particularly in mild DCM.

OBJECTIVE: To prospectively evaluate the impact of surgery on patient-reported outcomes in patients with mild (modified Japanese Orthopaedic Association [mJOA] ≥ 15), moderate (mJOA 12-14), and severe (mJOA < 12) DCM.

METHODS: Prospective, multicenter cohort study of patients with DCM who underwent surgery between 2015 and 2019 and completed 1-yr follow-up. Outcome measures (mJOA, Neck Disability Index [NDI], EuroQol-5D [EQ-5D], Short Form [SF-12] Physical Component Score [PCS]/Mental Component Score [MCS], numeric rating scale [NRS] neck, and arm pain) were assessed at 3 and 12 mo postoperatively and compared to baseline, stratified by DCM severity. Changes in outcome measures that were statistically significant (P < .05) and met their respective minimum clinically important differences (MCIDs) were deemed clinically meaningful. Responder analysis was performed to compare the proportion of patients between DCM severity groups who met the MCID for each outcome measure.

RESULTS: The cohort comprised 391 patients: 110 mild, 163 moderate, and 118 severe. At 12 mo after surgery, severe DCM patients experienced significant improvements in all outcome measures; moderate DCM patients improved in mJOA, NDI, EQ-5D, and PCS; mild DCM patients improved in EQ-5D and PCS. There was no significant difference between severity groups in the proportion of patients reaching MCID at 12 mo after surgery for any outcome measure, except NDI.

CONCLUSION: At 12 mo after surgery, patients with mild, moderate, and severe DCM all demonstrated improved outcomes. Severe DCM patients experienced the greatest breadth of improvement, but the proportion of patients in each severity group achieving clinically meaningful changes did not differ significantly across most outcome measures.

PMID:34382661 | DOI:10.1093/neuros/nyab295

Nucl Med Rev Cent East Eur. 2021;24(2):63-69. doi: 10.5603/NMR.2021.0017.

ABSTRACT

BACKGROUND: About 30% of patients with disseminated differentiated thyroid cancer (DTC) may experience a loss of iodine uptake. It is associated with higher aggressiveness of the tumour and a reduced 10-year survival rate. The diagnosis of non-radioiodine avid DTC metastases remains a diagnostic challenge. A helpful technique for this diagnosis is positron emission tomography with 2-[¹⁸F]fluoro-2-deoxy-D-glucose (PET/CT with [¹⁸F]FDG). On the other hand, there are still discussions about the clinical value of using exogenous thyroid-stimulating hormone (TSH) stimulation before PET/CT with [¹⁸F]FDG. The aim of the study was the assessment of the usefulness of PET/CT with [¹⁸F]FDG under TSH suppression and stimulation of TSH performed in the detection of non-radioiodine avid DTC metastases, as well as determination of the thyroglobulin concentration under suppression and stimulation of TSH, which influences the result of PET/CT with [¹⁸F]FDG in patients with non-radioiodine avid DTC.

MATERIAL AND METHODS: Retrospective analysis of 37 PET/CT with [¹⁸F]FDG performed in patients with DTC diagnosed and treated at the Department of Endocrinology and Isotope Therapy of the Military Institute of Medicine from January 2018 to July 2020. Of these, PET/CT with [¹⁸F]FDG under exogenous rhTSH stimulation was performed in 22 patients and PET/CT with [¹⁸F]FDG under TSH suppression in 15 was performed. In all analyzed patients, the result of diagnostic whole-body scintigraphy (WBS) using 80 MBq ¹³¹I under rhTSH stimulation was negative, and the concentration of thyroglobulin after stimulation (sTg) was greater than 1.0 ng/mL.

RESULTS: In the group of patients examined under TSH suppression, non-radioiodine avid in PET/CT with [¹⁸F]FDG were found in 6 out of 15 patients (40%) and in the group of patients examined under rhTSH stimulation in 10 out of 22 patients (45%). The differences between the groups were not statistically significant. The analysis of the receiver operating characteristic (ROC) curves allowed to determine the cut-off point for the positive result of PET/CT performed under TSH suppression with sTg concentration of 11.03 ng/mL. In the group of studies performed under rhTSH stimulation, the cut-off point for sTg was 6.3 ng/mL. There was no statistically significant difference between the baseline thyroglobulin (natTg) and sTg levels and the positive PET/CT result. The administration of rhTSH before the PET/CT examination also had no statistically significant effect on the maximum standard uptake value (SUVmax) of the dominant lesion identified in the PET/CT.

CONCLUSIONS: 1) PET/CT with [¹⁸F]FDG is a useful tool for detection of non-radioiodine avid recurrence and/or metastases of DTC. 2) The concentration of natTg and sTg is highly correlated with a positive result of PET/CT with [¹⁸F]FDG. 3) The concentration of natTg is comparable with sTg in predicting a positive result of PET/CT with [¹⁸F]FDG. 4) The cut-off point for a positive result of PET/CT for natTg was 1.36 ng/mL and for sTg was 7.05 ng/mL.

PMID:34382670 | DOI:10.5603/NMR.2021.0017

Health Serv Res. 2021 Aug 12. doi: 10.1111/1475-6773.13853. Online ahead of print.

ABSTRACT

OBJECTIVES: To (1) develop a survey to assess the patient experience of care in hospital-based emergency departments (ED) and (2) evaluate the reliability and validity of composite measures of patient experience using data collected through the experimental implementation of the newly developed Emergency Department Patient Experience of Care (EDPEC) Discharged to Community (DTC) Survey.

DATA SOURCE: 4893 adult patients were treated in the ED of 16 hospitals across the United States in 2018.

STUDY DESIGN: The study utilized a cross-sectional survey.

DATA COLLECTION: Survey development activities included a literature review, focus groups, and cognitive interviews with recently discharged ED patients, technical expert panels, and multiple field experiments. Survey development resulted in a 34-item instrument; the analysis reported here focuses on 18 items on patient experience of care. Using data from the EDPEC DTC Survey in the 2018 Feasibility Test, we performed confirmatory factor analysis to group 15 evaluative survey items into composite measures. We examined internal consistency reliability, interunit reliability, and associations between each composite measure and patients’ overall rating and willingness to recommend the ED.

PRINCIPAL FINDINGS: Analyses of 15 evaluative items identified four composite measures: Getting Timely Care, How Well Doctors and Nurses Communicate, Communication about Medications, and Communication about Follow-up. Patient-level internal consistency reliability exceeded 0.75 for two of four composites; ED-level internal consistency reliability exceeded 0.83 for all four composites. Interunit reliability estimates indicated that 450 survey completes per ED results in at least 0.70 reliability for all composites. Higher scores on each composite were associated with higher overall ratings and willingness to recommend the ED.

CONCLUSIONS: The composite measures derived from the EDPEC DTC Survey are statistically reliable and valid. These results provide guidance for EDPEC DTC Survey adopters on how to construct meaningful and psychometrically-sound composite measures for monitoring the quality of care they provide.

PMID:34382685 | DOI:10.1111/1475-6773.13853

J Clin Endocrinol Metab. 2021 Aug 12:dgab564. doi: 10.1210/clinem/dgab564. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to determine the procalcitonin (ProCT) diagnostic accuracy in prediction and treatment monitoring of medullary thyroid carcinoma (MTC).

DATA SOURCES: Electronic databases were searched for observational studies published until May 2021 without language or time restrictions.

STUDY SELECTION: Studies comparing ProCT and calcitonin accuracy were included. After removing duplicates and exclusion of not-eligible articles, relevant articles were screened independently by two reviewers. Eleven studies (4.5% of the identified studies) met the selection criteria.

DATA EXTRACTION: Two reviewers independently extracted data and assessed data quality and validity through QUADAS-2.

DATA SYNTHESIS: A meta-analysis was performed on sufficiently clinically and statistically homogeneous eleven studies (n = 5817 patients, 335 MTC patients). HSROC and bivariate methods were applied. Serum ProCT was found to be a highly accurate test for MTC diagnosis and monitoring. The pooled sensitivity, specificity, positive and negative likelihood ratios, AUC, and positive and negative predictive values for ProCT were 0.90 (95%CI: 0.71-0.97), 1.00 (95%CI: 0.85-1.00), 288 (95%CI: 5.6-14929.3), 0.10 (95%CI: 0.03-0.33), 0.97 (95%CI: 0.95-0.98), 99% and 2%.

CONCLUSIONS: The high accuracy, compounded with favorable analytical characteristics, give ProCT great potential to replace calcitonin as a new standard of care in the management of MTC.

PMID:34382653 | DOI:10.1210/clinem/dgab564

J Gerontol A Biol Sci Med Sci. 2021 Aug 12:glab212. doi: 10.1093/gerona/glab212. Online ahead of print.

ABSTRACT

Quantifying the physiology of aging is essential for improving our understanding of age-related disease and the heterogeneity of healthy aging. Recent studies have shown that in regression models using “-omic” platforms to predict chronological age, residual variation in predicted age is correlated with health outcomes, and suggest that these “omic clocks” provide measures of biological age. This paper presents predictive models for age using metabolomic profiles of cerebrospinal fluid from healthy human subjects, and finds that metabolite and lipid data are generally able to predict chronological age within 10 years. We use these models to predict the age of a cohort of subjects with Alzheimer’s and Parkinson’s disease and find an increase in prediction error, potentially indicating that the relationship between the metabolome and chronological age differs with these diseases. However, evidence is not found to support the hypothesis that our models will consistently over-predict the age of these subjects. In our analysis of control subjects, we find the carnitine shuttle, sucrose, biopterin, vitamin E metabolism, tryptophan, and tyrosine to be the most associated with age. We showcase the potential usefulness of age prediction models in a small dataset (n = 85), and discuss techniques for drift correction, missing data imputation, and regularized regression, which can be used to help mitigate the statistical challenges that commonly arise in this setting. To our knowledge, this work presents the first multivariate predictive metabolomic and lipidomic models for age using mass spectrometry analysis of cerebrospinal fluid.

PMID:34382643 | DOI:10.1093/gerona/glab212

Am J Hypertens. 2021 Aug 12:hpab129. doi: 10.1093/ajh/hpab129. Online ahead of print.

ABSTRACT

BACKGROUND: Blood pressure (BP) control was only 43.7% in the National Health and Nutrition Survey (NHANES) survey in 2017-2018. Scalable, non-clinic-based strategies to control BP are needed. We therefore conducted a pilot trial of a text-messaging intervention in a national network of retail outlet health kiosks with BP devices. All study procedures were conducted remotely.

METHODS: Eligible individuals (N=140), based on average BP >140/90 mmHg at kiosks during the prior year, were randomized to intervention vs. usual care. Intervention consisted of tailored text messages providing educational information with embedded links to educational videos on topics related to BP control. BP measurements were obtained at kiosks at 3, 6, and 12 months following randomization; control was defined as BP <140/90 mmHg. Follow-up at 12 months was curtailed due to SARS-CoV-2. We therefore combined 12-month (N=62) or carried forward 6-month (N=61) data as the primary endpoint.

RESULTS: Participants were 51.4% male, 70.7% white/Caucasian, had mean age of 52.1 years, and mean baseline BP 145.5/91.8 mmHg. At the endpoint, 37.7% intervention vs. 27.4% usual care subjects achieved BP control (difference, 10.3%, 95% CI -6.2%, 26.8%). In an intention-to-treat analysis with multiple imputation of missing data, 12-month BP control was 29.0% vs. 19.8% favoring intervention (difference, 9.2%. 95% CI -7.3%, 25.7%); intervention vs. control differences in adjusted mean BP levels were SBP: -5.4 mmHg (95% CI: -13.5, 2.7) and DBP: +0.6 mmHg (95% CI: -4.2, 5.4).

CONCLUSIONS: These pilot results support the potential for a highly scalable text-messaging intervention to improve BP.

PMID:34382648 | DOI:10.1093/ajh/hpab129

J Biomech Eng. 2021 Aug 12. doi: 10.1115/1.4052110. Online ahead of print.

ABSTRACT

Repair of severed nerves without auto- or allograft has included suture, suture with glue alone, suture with conduit and suture with glue augmentation to conduit, where use of conduit is considered for separation of the nerve ends from 5mm to 3cm. Repairs must not only serve acutely to provide apposition of nerve ends but must enable the healing of the nerve. Using biological conduit can place suture at the ends of the conduit while fibrin glue alone eliminates suture but with limited strength. The combination of conduit and glue offers the growth guidance of conduit with sufficient strength from the glue to maintain the nerve within the conduit. The role of glue in the repair integrity remains an open question, however. We sought to determine the factors in the strength of a glue-conduit-nerve construct and include consideration of standard suture repair. Fresh-frozen cadaveric digital nerves were repaired with suture alone, with glue alone or with suture and glue together and loaded to failure. Previously tested specimens with conduit, suture and glue were considered for comparison. The suture alone (2.02N) and suture with glue (2.24N) were not statistically different from each other but were statistically stronger than glue alone (0.15N). Compared to the earlier results of the strength of conduit with glue (0.65N), these results show that the glue and conduit act together. The increased area over which the glue adheres to the nerve and conduit creates a composite structure stronger than either alone.

PMID:34382652 | DOI:10.1115/1.4052110