Tag: statistics

Lancet Neurol. 2021 Mar 23:S1474-4422(21)00027-2. doi: 10.1016/S1474-4422(21)00027-2. Online ahead of print.

ABSTRACT

BACKGROUND: The European Friedreich’s Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich’s ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich’s ataxia.

METHODS: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich’s ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509.

FINDINGS: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be required to detect a 50% reduction in SARA progression at 80% power: 118 (59 per group) if only individuals who are ambulatory are included. With ADL as the primary outcome, 190 (95 per group) patients with Friedreich’s ataxia would be needed, and fewer patients would be required if only individuals with early-onset are included.

INTERPRETATION: Our findings for stage-dependent progression rates have important implications for clinicians and researchers, as they provide reliable outcome measures to monitor disease progression, and enable tailored sample size calculation to guide upcoming clinical trial designs in Friedreich’s ataxia.

FUNDING: European Commission, Voyager Therapeutics, and EuroAtaxia.

PMID:33770527 | DOI:10.1016/S1474-4422(21)00027-2

Clin Biomech (Bristol, Avon). 2021 Mar 15;84:105323. doi: 10.1016/j.clinbiomech.2021.105323. Online ahead of print.

ABSTRACT

BACKGROUND: Two populations commonly presenting with equinus gait are Idiopathic Toe-Walkers and children with Cerebral Palsy. Surgical intervention to treat equinus is defined by three zones. Zone three surgery, performed at the Achilles tendon, is most commonly used clinically. There is however, evidence from simulation studies that zone two surgery, performed at the muscle belly, might provide better functional outcomes. The purpose of this study was to investigate the effect of zone two calf-lengthening on post-operative gait in these populations.

METHODS: A retrospective audit of the Queensland Children’s Motion Analysis Service database identified 17 toe-walkers (mean age 10.13 (SD 2.625)) and 11 Cerebral Palsy (mean age 9.72 (SD 4.04)) participants that received calf-lengthening surgery for plantarflexion contracture and had pre- and post-surgery 3D gait analysis. Inverse kinematics, dynamics, and muscle analysis were performed in OpenSim (v3.3) using a modified gait2392 model. Pre to post-surgery comparisons were performed in MATLAB using statistical parametric mapping. Dependent variables included ankle kinematics, powers and muscle-tendon length estimates.

FINDINGS: The primary outcome of this study was that ankle dorsiflexion increased in both Idiopathic Toe Walking and Cerebral Palsy groups post-calf lengthening across 90% and 85% of the gait cycle respectively. There was an increase in modelled muscle-tendon lengths, specifically in the medial gastrocnemius, of 78% (toe-walkers), and 100% (Cerebral Palsy) of the gait cycle. Power generation during push-off was not affected.

INTERPRETATION: Overall, the results appear to support the efficacy of zone 2 calf-lengthening for children with Cerebral Palsy and Idiopathic Toe Walking.

PMID:33770533 | DOI:10.1016/j.clinbiomech.2021.105323

Clin Imaging. 2021 Mar 19;78:60-63. doi: 10.1016/j.clinimag.2021.02.040. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate whether, with access to free screening services, uninsured minority women in NYC are able to successfully manage existing barriers to breast cancer screening.

METHODS: This is a retrospective cohort study, with permission to use de-identified data received from Project Renewal’s ScanVan in 2019. Project Renewal ScanVan provides clinical breast exams, mammograms, and health education to low-income women. The screening mammograms were conducted in the ScanVan and read by a board-certified radiologist. The electronic medical records were reviewed with respect to the patients’ BI-RADS category, insurance status, race, and age. Descriptive statistics were performed and cancer detection rate, recall rate, and positive predictive values (PPV1, PPV2, PPV3) were calculated.

RESULTS: In 2019, 66% (2499 of 3745) of patients who used the ScanVan were Hispanic & African American. 43% (1627 of 3745) of the women were uninsured, 15% (579 of 3745) of the women had Medicare, and 18% (676 of 3745) classified as other. 17 out of 3745 patients screened received a new diagnosis of breast cancer, corresponding to a cancer detection rate of 4.5/1000 screened. 258 were recalled, corresponding with a recall rate of 7%. The PPV1 was 6.5% (17/258); PPV2 was 29.8% (17/57); and PPV3 was 34% (17/50).

CONCLUSION: Barriers to breast cancer screening include lack of medical insurance, limited access to care, and the absence of a primary care physician. The mobile mammography screening van successfully overcame such barriers, providing uninsured women from racial minority groups with vital breast cancer screening and follow up care.

PMID:33770557 | DOI:10.1016/j.clinimag.2021.02.040

Arthritis Care Res (Hoboken). 2021 Mar 26. doi: 10.1002/acr.24607. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop and validate a composite RA disease activity index using optical spectral transmission (OST)-scores obtained with the HandScan replacing tender and swollen joint counts.

METHODS: RA patients from a single centre routinely undergoing HandScan measurements and at least one concurrent OST-score and DAS28 were included. Data was extracted from medical records. Linear regression analyses with DAS28 as outcome were performed to create a disease activity index (DAS-OST). OST-score, ESR and patient global assessment (PGA-)VAS, gender, age, disease duration and RF-status were evaluated as independent variables. Final models were derived, based on statistical significance of coefficients and model fit. Of the data, 2/3 was used for development and 1/3 for validation; external validation was performed in a cohort from another centre. Agreement between DAS-OST and DAS28 was assessed using the Bland-Altman plot method and intra-class correlation coefficient (ICC). Diagnostic value of DAS-OST was determined for established definitions of remission, and low (L), and high (H) disease activity (DA).

RESULTS: Data of 3358 observations from 1505 unique RA patients were extracted. DAS-OST was defined as: -0.44 + OST*0.03 + male*-0.11 + LN(ESR)*0.77 + PGA-VAS*0.03. The ICC between DAS-OST and DAS28 were 0.88 (95%CI 0.87-0.90) and 0.82 (95%CI 0.75-0.86) and measurement errors 0.58 and 0.87 in internal and external validation, respectively. Sensitivity for remission, LDA and HDA were 79%, 91%, 43%, and specificity 92%, 80%, 96% in external validation.

CONCLUSION: Using the HandScan, RA disease activity can be accurately estimated if combined with ESR, PGA-VAS and gender into a disease activity index (DAS-OST).

PMID:33770421 | DOI:10.1002/acr.24607

Psychometrika. 2021 Mar 26. doi: 10.1007/s11336-021-09752-7. Online ahead of print.

ABSTRACT

In this article, we present the findings of an oral history project on the past, present, and future of psychometrics, as obtained through structured interviews with twenty past Psychometric Society presidents. Perspectives on how psychometrics should be practiced vary strongly. Some presidents are psychology-oriented, whereas others have a more mathematical or statistical approach. The originally strong relationship between psychometrics and psychology has weakened, and contemporary psychometrics has become a diverse and multifaceted discipline. The presidents are confident psychometrics will continue to be relevant but believe psychometrics needs to become better at selling its strong points to relevant research areas. We recommend for psychometrics to cherish its plurality and make its goals and priorities explicit.

PMID:33770319 | DOI:10.1007/s11336-021-09752-7

J Neurooncol. 2021 Mar 26. doi: 10.1007/s11060-021-03746-2. Online ahead of print.

ABSTRACT

INTRODUCTION: Esthesioneuroblastoma (ENB) is an uncommon primary sinonasal tumor which can extend intracranially. Exactly how to classify them pathologically still remains discrepant; the Hyams grading system, for example, has not been universally adopted. This individual patient data (IPD) meta-analysis aimed to investigate the prognostic implication of each Hyams grade on patient outcomes.

METHODS: We accessed two electronic databases including PubMed and Web of Science. Raw patient data from potential articles were extracted. To examine the associations of various clinicopathological factors with the Hyams grades, we utilized Chi-square, t-test, and Mann-Whitney, as appropriate. Log-rank test and Cox regression analysis were used to elucidate the impact of the Hyams grades on recurrence-free survival (RFS), metastasis-free survival (MFS), and overall survival (OS) of ENB patients.

RESULTS: We included 33 studies with 492 ENB patients. We found significant associations of Kadish stages, Dulguerov stages, rates of recurrence, metastasis, and patient mortality with Hyams grade. Log-rank tests and Cox regression models demonstrated significant differences in RFS and OS of Hyams grade I – II, grade III, and grade IV patients. There was no statistical difference in RFS and OS of Hyams grade I and II. Radiotherapy was only effective in grade III – IV ENBs and chemotherapy showed no benefits to patients.

CONCLUSION: We verify that the Hyams grading system appears to be a reliable prognostic indicator to assess ENB patient outcomes. Consolidating the Hyams grading system into a three-tier system based on similar clinical outcomes of grades I and II may simplify this classification schema.

PMID:33770323 | DOI:10.1007/s11060-021-03746-2

Ann Nucl Med. 2021 Mar 26. doi: 10.1007/s12149-021-01608-5. Online ahead of print.

ABSTRACT

AIM: To evaluate the use of digital ¹⁸F-FDG PET/CT with small-voxels reconstruction for detecting in-transit metastases in melanoma patients with primary lesion located on the upper or lower limbs, in comparison with standard reconstruction and European Association of Nuclear Medicine Research limited (EARL)-compliant reconstruction mimicking former generation PET systems.

METHODS: Forty-six PET examinations acquired in list mode on a Vereos digital PET/CT system were reconstructed with (1) the standard reconstruction [2 iterations, 10 subsets (2i10s), point-spread function (PSF) modelling and time-of-flight enabled, no post-filtering and voxel size of 2 mm], (2) a small-voxel reconstruction using 1 mm voxels otherwise using the same parameters, (3) an EARL-compliant reconstruction mimicking a former generation system. Comparison of results across these reconstructions was made for a blind randomized review using a 3-point scale for the presence of in-transit metastases and image quality as well as for tumour-to-background (T/B) ratios and noise level in reference organs.

RESULTS: Seven of the thirty-two EARL-compliant images classified as negative moved to positive on 1mm_PSF images, and 5 of the 6 EARL-compliant images classified as indeterminate moved to positive on 1mm_PSF images (P = 0.01). Amongst a total of 20 PET examinations classified as positive using the 1mm_PSF reconstruction, fifteen were considered true positive, five false positive results occurred. Twenty-four patients with 1 mm PSF images were classified as negative, none of those under active surveillance experienced in-transit metastases during the 17 months following their PET examination. The positive likelihood ratio for the 1 mm reconstruction was much higher than that observed for EARL-compliant images (14.7 vs 7.82). Importantly, negative likelihood ratios for the 1 mm and 1mm_PSF reconstruction were almost perfect. Compared to EARL-compliant data, T/B ratios extracted from the 1mm_PSF showed a 2.84-fold increase (P < 0.001). A similar pattern of statistically significant increase was observed for noise level in organs of reference. Image quality for the torso was found to be significantly lower for 1mm_PSF reconstruction (P = 0.03). Image quality for the limbs was found to be better for 1mm_PSF (P < 0.001).

CONCLUSION: Digital PET with small-voxel reconstruction brings an additional value for the detection of in-transit metastases by reducing the number of indeterminate findings and making up for falsely negative scans using former generation PET systems. An acquisition encompassing lower or upper limbs as appropriate should be performed.

PMID:33770374 | DOI:10.1007/s12149-021-01608-5

Mol Biol Rep. 2021 Mar 26. doi: 10.1007/s11033-021-06292-2. Online ahead of print.

ABSTRACT

Venustaconcha ellipsiformis (Unionidae) is a freshwater mussel species inhabiting small to medium streams of the Midwestern United States; however, its occurrence is rather sporadic and populations are often isolated. Due to anthropogenic habitat degradation and water pollution, this species is designated as some sort of conservation status in many states. To prioritize conservation strategies, highly variable genetic markers are necessary to assess population genetic structure and potential genetic erosion of V. ellipsiformis. Using whole genome sequence data, we developed and characterized microsatellite markers for V. ellipsiformis. Among 23 tetranucleotide loci tested, 14 loci were consistently amplified and showed polymorphism. Analyses performed on three populations in the upper Mississippi River basin showed that the number of alleles per locus ranged from 2 to 11 and the observed heterozygosity varied from 0.15 to 0.75. Based on genotypic and allelic rarefaction curves, these loci had adequate statistical power to genetically discriminate between individuals and the sample size was large enough to capture most alleles available in the populations at most loci. Finally, cross-species screening of the loci successfully amplified and showed polymorphism in six species in the tribe Lampsilini. The microsatellite loci developed in this study provide a valuable addition to extant genetic markers for freshwater mussels and can be useful to provide high-level resolution of population genetic parameters for V. ellipsiformis. Such information will be of great value for resource managers developing and prioritizing conservation strategies for imperiled mussel species.

PMID:33770294 | DOI:10.1007/s11033-021-06292-2

Environ Geochem Health. 2021 Mar 26. doi: 10.1007/s10653-021-00882-6. Online ahead of print.

ABSTRACT

In arid and semiarid regions, groundwater is required for the drinking, agriculture, and industrial activities due to scarcity of surface water. Groundwater contaminated with high concentrations of fluoride and nitrate can severely affect human health in these regions. Twenty-eight groundwater samples from rural habitations of Jhunjhunu district, Rajasthan, India, were collected in March 2018 and subjected to analysis for water quality parameters. Fluoride and nitrate concentrations in groundwater varied from 0 to 5.74 mg/L and 10.22-519.64 mg/L, respectively. Nitrate content of about 86% samples and fluoride content of about 54% exceeded the permissible limit of Bureau of Indian Standards (IS:10,500) as well as World Health Organization standards. All groundwater samples belonged to poor to unfit drinking water quality index. Principle component analysis elucidates the anthropogenic contribution to high nitrate concentrations observed in this area. Noncarcinogenic human health risk evaluated from high nitrate and fluoride in drinking water for children, men, and women points to the fact that noncarcinogenic risk is exceeding the allowable limit to human health. The predominating hydrochemical facies in the area is Na⁺-HCO₃^–-Cl^– followed by Na⁺-Mg²⁺-HCO₃^–-Cl^–. The Gibbs plot and bivariate ionic cross-plots suggest the noncarbonate weathering (rock dominance), evaporation dominance, and ion exchange process to be the predominating geochemical mechanisms governing the evolution of groundwater hydrogeochemistry. Giggenbach diagram shows the immature character, i.e., incomplete equilibration of the groundwater.

PMID:33770299 | DOI:10.1007/s10653-021-00882-6

Biomech Model Mechanobiol. 2021 Mar 26. doi: 10.1007/s10237-021-01444-6. Online ahead of print.

ABSTRACT

This paper aims to investigate detailed mechanical interactions between the pulmonary haemodynamics and left heart function in pathophysiological situations (e.g. atrial fibrillation and acute mitral regurgitation). This is achieved by developing a complex computational framework for a coupled pulmonary circulation, left atrium and mitral valve model. The left atrium and mitral valve are modelled with physiologically realistic three-dimensional geometries, fibre-reinforced hyperelastic materials and fluid-structure interaction, and the pulmonary vessels are modelled as one-dimensional network ended with structured trees, with specified vessel geometries and wall material properties. This new coupled model reveals some interesting results which could be of diagnostic values. For example, the wave propagation through the pulmonary vasculature can lead to different arrival times for the second systolic flow wave (S2 wave) among the pulmonary veins, forming vortex rings inside the left atrium. In the case of acute mitral regurgitation, the left atrium experiences an increased energy dissipation and pressure elevation. The pulmonary veins can experience increased wave intensities, reversal flow during systole and increased early-diastolic flow wave (D wave), which in turn causes an additional flow wave across the mitral valve (L wave), as well as a reversal flow at the left atrial appendage orifice. In the case of atrial fibrillation, we show that the loss of active contraction is associated with a slower flow inside the left atrial appendage and disappearances of the late-diastole atrial reversal wave (AR wave) and the first systolic wave (S1 wave) in pulmonary veins. The haemodynamic changes along the pulmonary vessel trees on different scales from microscopic vessels to the main pulmonary artery can all be captured in this model. The work promises a potential in quantifying disease progression and medical treatments of various pulmonary diseases such as the pulmonary hypertension due to a left heart dysfunction.

PMID:33770307 | DOI:10.1007/s10237-021-01444-6