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Nevin Manimala Statistics

The Application of H-Loop in Arthroscopic Knotless Double-Row Rotator Cuff Repairs

Orthop Surg. 2021 Oct 1. doi: 10.1111/os.13107. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the functional outcomes after a novel method of H-loop knotless double-row technique in patients with rotator cuff tears.

METHOD: From June 2020 to September 2020, a total of six patients (five women, one man) with arthroscopic rotator cuff repair using the H-loop knotless double-row technique were enrolled in our study. The average age is 54 years (range: 50-61 years). The preoperative and final follow-up clinical outcome were evaluated using the American Shoulder and Elbow Surgeons (ASES) score, visual analog scale (VAS), University of California Los Angeles (UCLA) score, and Constant-Murley score. The active shoulder range of motion (ROM) was also collected preoperatively and postoperatively at the final follow-up (forward flexion and abduction). Accordingly, intraoperative and postoperative complications were observed as well.

RESULT: There were six patients that underwent arthroscopic rotator cuff repair using the H-loop knotless double-row technique. The average follow-up period was 7.52 ± 0.70 months. The VAS, UCLA, ASES, and Constant-Murley scores improved from 5 ± 2.45, 15.67 ± 3.44, 47.67 ± 17.41 and 49.17 ± 8.98 preoperatively, to 0.83 ± 0.75, 36.27 ± 3.83, 91.67 ± 10.76 and 85.83 ± 4.31 at the final follow-up, with statistical significances of P = 0.009, P < 0.001, P = 0.006, and P = 0.001, respectively. Meanwhile, the active shoulder ROM (forward flexion and abduction) improved from 135.00 ± 46.80 and 125 ± 56.48 preoperatively, to 173.67 ± 4.13 and 172 ± 3.27 at final follow-up, respectively (P = 0.082, P = 0.088). During the follow-up, there were no postoperative complications such as wound-site infection, nerve or vessel damage, subcutaneous hematoma, and suture anchor problems.

CONCLUSION: With the benefit of reducing the possibility of strangulation and blood supply affection for the rotator cuff, The H-loop knotless double row technique may be an alternative method to significantly improve subjective functional outcomes and increase the healing rate of medium-sized rotator cuff tears with degeneration issues and poor tissue quality.

PMID:34596353 | DOI:10.1111/os.13107

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Nevin Manimala Statistics

Population structure and pattern of geographic differentiation of Colorado Potato Beetle, Leptinotarsa decemlineata (Coleoptera: Chrysomelidae) in Turkey

Pest Manag Sci. 2021 Oct 1. doi: 10.1002/ps.6663. Online ahead of print.

ABSTRACT

BACKGROUND: The Colorado potato beetle (CPB) is the most harmful pest of potato in potato cultivation regions globally. Although it is an economically important agricultural pest, the population structure and colonization route of this species in Turkey are uncertain. We used microsatellite and mtDNA markers to obtain information about the population source, structure and bio-invasion route of CPB populations in Turkey.

RESULTS: The common single mtDNA haplotype in European CPB populations was obtained in all Turkish CPB populations based on mtDNA data analysis. However, microsatellites revealed a low level of genetic variation in CPB populations. The results of microsatellite analysis (FCA, BAPS, UPGMA dendrogram, F-statistics and Nei’s distances) indicated three groups for invasive CPB: Thrace-Marmara and Aegean; Black Sea, Central Anatolia and Mediterranean; Northeastern Anatolia. Region-specific alleles have been identified in regions, where commercial potato cultivation and insecticide use are intensive.

CONCLUSION: The detection of a single fixed European haplotype in all Turkish populations has proved that CPB in Turkey originated from Europe as a result of a founder event occurred in European populations. Low genetic variation was due to the short time period since the spread of CPB from America to Europe. The highest number of private alleles were found in the top commercial potato cultivation region-Central Anatolia from where the CPB populations spread to other parts of Turkey. This article is protected by copyright. All rights reserved.

PMID:34596319 | DOI:10.1002/ps.6663

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Nevin Manimala Statistics

Changes in peripheral blood in SARS CoV-2 patients and its clinico-pathological correlation: A prospective cross-sectional study

Int J Lab Hematol. 2021 Oct 1. doi: 10.1111/ijlh.13720. Online ahead of print.

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV2 can present from mild flu-like symptoms to acute respiratory distress syndrome. There is multi-organ involvement; particularly, hematopoietic system can be associated with morphological changes in blood cells of COVID-19 patients.

METHOD: We conducted a cross-sectional study on a cohort of 50 COVID-19 patients, confirmed on RT-PCR with documented cycle threshold (Ct) value. Peripheral blood sample of these patients was collected and examined for complete blood counts (CBC) on automated haematological analyser as well as Leishman-stained blood smears to look for morphological changes in blood cells. Morphological changes were evaluated with reference to clinical severity and Ct value. Additionally, association between Ct value and clinical severity was also performed. Statistical tests were performed, and P value <.05 was considered significant.

RESULTS: Mean age of our study group was 42.16 ± 15.55 years, with male preponderance. Most commonly observed peripheral blood changes were hypolobation (P value = .002) and toxic granules (P value = .005) in neutrophils, atypical granules with nucleolar prominence in lymphocytes, cytoplasmic granulation with clumped nuclear chromatin in monocytes, giant platelets and thrombocytopenia and normocytic normochromic anaemia.

CONCLUSION: No association was found between clinical severity and Ct value as well as peripheral blood morphological changes with Ct value. We conclude that examination of peripheral smear coupled with complete blood count (CBC) is only partially supportive of disease pathogenesis and to assess the viral load other parameters should be utilised instead of relying solely on Ct value.

PMID:34596329 | DOI:10.1111/ijlh.13720

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Direct effect of transforming growth factor-beta 1 (TGF-β1) on human apical papilla cell proliferation and mineralisation

Aust Endod J. 2021 Oct 1. doi: 10.1111/aej.12572. Online ahead of print.

ABSTRACT

Firstly, this study investigated the direct effect of Transforming Growth Factor-beta 1 at 10, 5, 2.5 and 1.25 ng mL-1 on human apical papilla cell proliferation and mineralisation. Cell proliferation was examined at 0, 2, 4, 6, 24, 48, 72, 96 and 120 h using Alamar BlueTM assay. Cell mineralisation was examined at day 21 with a quantitative Alizarin Red S staining. Secondly, the study aimed to estimate the amount of Transforming Growth Factor-beta 1 (TGF-β1) released from the dentin after root canal irrigation. The solution collected from a root canal after rinsing with various protocols (normal saline solution, ethylenediaminetetraacetic acid or chlorhexidine) was analysed with an enzyme-linked immunosorbent assay. Data were statistically analysed using a one-way analysis of variance. The results, from the first part, revealed cell proliferation reduction in all experimental groups presented with TGF-β1. The higher concentration generated more deteriorating effects. Cell mineralisation was highest in a group with TGF-β1 at 1.25 ng mL-1 (P < 0.05). For the growth factor released from dentin, the highest amount was detected only when ethylenediaminetetraacetic acid was associated with the irrigation (P < 0.05). In summary, the direct effects of TGF-β1 on cell proliferation and differentiation were diverse, depending on concentration. The release of TGF-β1 from root dentin can be achieved after rinsing with ethylenediaminetetraacetic acid.

PMID:34596309 | DOI:10.1111/aej.12572

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Nevin Manimala Statistics

Large-scale group genetic counseling: Evaluation of a novel service delivery model in a Canadian hereditary cancer clinic

J Genet Couns. 2021 Oct 1. doi: 10.1002/jgc4.1512. Online ahead of print.

ABSTRACT

Increasing demand for genetic services has led to the development of streamlined genetic counseling (GC) models. We piloted large-scale group pre-test GC with up to 50 patients per group and compared this to a traditional one-on-one approach. Patients referred to the British Columbia (BC) Cancer Hereditary Cancer Program were eligible if they had: (a) family history meeting our program’s referral criteria; (b) no relevant personal history of cancer; (c) no prior genetic testing in the family; and (d) no living testable relative in BC. Patient-reported outcome measures included: (a) Genetic Counselling Outcome Scale (GCOS) prior to pre-test GC (T1) and at 4 weeks post-test GC (T2); (b) Satisfaction Survey after pre-test GC; and (c) the Multidimensional Impact of Cancer Risk Assessment (MICRA) for patients undergoing testing (4 weeks after post-test GC). In total, 391 patients underwent GC, 184 by group and 207 by one-on-one appointments. Between May 2018 and May 2019, 6 pre-test group sessions were conducted (median number of patients per group = 28; range 15-48). 8% of patients (n = 32) declined large group GC due to personal preference for one-on-one GC. There were no statistically significant differences in MICRA and GCOS survey results when comparing the pre-test large group versus traditional pre-test one-on-one models (based on 3 MICRA subscales: p = 0.063, p = 0.612, p = 0.842; and GCOS p = 0.169). Overall, the large group pre-test counseling approach was more time-efficient with 15-48 patient group sessions conducted over a mean duration of 80 min as compared to 42 min per patient with the traditional one-on-one GC model. Large-scale group GC was feasible and acceptable to patients and represents a novel streamlined model for GC to enable timely access to cancer genetic services.

PMID:34596310 | DOI:10.1002/jgc4.1512

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Are current cut-off values of 11-DOC in children useful for assessing suspected nonclassical congenital adrenal hyperplasia due to 11β-hydroxylase deficiency?

Clin Endocrinol (Oxf). 2021 Oct 1. doi: 10.1111/cen.14597. Online ahead of print.

ABSTRACT

OBJECTIVE: A nonclassic form of 11β-hydroxylase deficiency (NC11β-OHD) has been reported to cause mild androgen excess symptoms. Currently, the gold standard for biochemical diagnosis is elevated 11-deoxycortisol (11-DOC) levels after corticotropin stimulation test (ACTHstimT). However, there are no clear 11-DOC level cutoffs. One of the accepted references for 11-DOC levels for the paediatric population was published in 1991 by Lashansky et al. AIM: To determine the correlation between 11-DOC levels measured during ACTHstimT and clinical symptoms attributed to NC11β-OHD.

DESIGN: A retrospective study including all paediatric patients who underwent ACTHstimT at Shamir Medical Center between 2007 and 2015. Clinical data were collected from the patients’ medical files. Outcome measures included the number of patients with hyperandrogenism signs and predefined elevated 11-DOC cut-off levels according to Lashansky for sex and age, and according to commercial kit cut-offs.

RESULTS: Data were complete at presentation for 136 patients. Long-term clinical data were documented for 98 patients, mean follow-up duration of 3.1 years (1.37-5.09). There was no statistically significant difference in the number of cases with elevated 11-DOC according to both cut-offs and early puberty, premature adrenarche nor acne. Follow-up data demonstrated no statistically significant difference in the number of cases with elevated 11-DOC levels among patients with compromised final adult height, polycystic ovarian syndrome or hyperandrogenism.

CONCLUSIONS: Basal and corticotropin stimulated 11-DOC levels were not significantly elevated above the 1.5 times cut-offs according to paediatric-specific norms or the commercial assay in paediatric individuals with possible clinical suspicion of NC11β-OHD.

PMID:34596265 | DOI:10.1111/cen.14597

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Nevin Manimala Statistics

A General Model to Calculate the Spin-Lattice Relaxation Rate (R1) of Blood, Accounting for Hematocrit, Oxygen Saturation, Oxygen Partial Pressure, and Magnetic Field Strength Under Hyperoxic Conditions

J Magn Reson Imaging. 2021 Oct 1. doi: 10.1002/jmri.27938. Online ahead of print.

ABSTRACT

BACKGROUND: Under normal physiological conditions, the spin-lattice relaxation rate (R1) in blood is influenced by many factors, including hematocrit, field strength, and the paramagnetic effects of deoxyhemoglobin and dissolved oxygen. In addition, techniques such as oxygen-enhanced magnetic resonance imaging (MRI) require high fractions of inspired oxygen to induce hyperoxia, which complicates the R1 signal further. A quantitative model relating total blood oxygen content to R1 could help explain these effects.

PURPOSE: To propose and assess a general model to estimate the R1 of blood, accounting for hematocrit, SO2 , PO2 , and B0 under both normal physiological and hyperoxic conditions.

STUDY TYPE: Mathematical modeling.

POPULATION: One hundred and twenty-six published values of R1 from phantoms and animal models.

FIELD STRENGTH/SEQUENCE: 5-8.45 T.

ASSESSMENT: We propose a two-compartment nonlinear model to calculate R1 as a function of hematocrit, PO2 , and B0. The Akaike Information Criterion (AIC) was used to select the best-performing model with the fewest parameters. A previous model of R1 as a function of hematocrit, SO2 , and B0 has been proposed by Hales et al, and our work builds upon this work to make the model applicable under hyperoxic conditions (SO2 > 0.99). Models were assessed using the AIC, mean squared error (MSE), coefficient of determination (R2 ), and Bland-Altman analysis. The effect of volume fraction constants WRBC and Wplasma was assessed by the SD of resulting R1. The range of the model was determined by the maximum and minimum B0, hematocrit, SO2 , and PO2 of the literature data points.

STATISTICAL TESTS: Bland-Altman, AIC, MSE, coefficient of determination (R2 ), SD.

RESULTS: The model estimates agreed well with the literature values of R1 of blood (R2 = 0.93, MSE = 0.0013 s-2 ), and its performance was consistent across the range of parameters: B0 = 1.5-8.45 T, SO2 = 0.40-1, PO2 = 30-700 mmHg.

DATA CONCLUSION: Using the results from this model, we have quantified and explained the contradictory decrease in R1 reported in oxygen-enhanced MRI and oxygen-delivery experiments.

LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

PMID:34596290 | DOI:10.1002/jmri.27938

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Two-phase sample selection strategies for design and analysis in post-genome-wide association fine-mapping studies

Stat Med. 2021 Oct 1. doi: 10.1002/sim.9211. Online ahead of print.

ABSTRACT

Post-GWAS analysis, in many cases, focuses on fine-mapping targeted genetic regions discovered at GWAS-stage; that is, the aim is to pinpoint potential causal variants and susceptibility genes for complex traits and disease outcomes using next-generation sequencing (NGS) technologies. Large-scale GWAS cohorts are necessary to identify target regions given the typically modest genetic effect sizes. In this context, two-phase sampling design and analysis is a cost-reduction technique that utilizes data collected during phase 1 GWAS to select an informative subsample for phase 2 sequencing. The main goal is to make inference for genetic variants measured via NGS by efficiently combining data from phases 1 and 2. We propose two approaches for selecting a phase 2 design under a budget constraint. The first method identifies sampling fractions that select a phase 2 design yielding an asymptotic variance covariance matrix with certain optimal characteristics, for example, smallest trace, via Lagrange multipliers (LM). The second relies on a genetic algorithm (GA) with a defined fitness function to identify exactly a phase 2 subsample. We perform comprehensive simulation studies to evaluate the empirical properties of the proposed designs for a genetic association study of a quantitative trait. We compare our methods against two ranked designs: residual-dependent sampling and a recently identified optimal design. Our findings demonstrate that the proposed designs, GA in particular, can render competitive power in combined phase 1 and 2 analysis compared with alternative designs while preserving type 1 error control. These results are especially evident under the more practical scenario where design values need to be defined a priori and are subject to misspecification. We illustrate the proposed methods in a study of triglyceride levels in the North Finland Birth Cohort of 1966. R code to reproduce our results is available at github.com/egosv/TwoPhase_postGWAS.

PMID:34596256 | DOI:10.1002/sim.9211

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Nevin Manimala Statistics

Development of a new pharmacokinetic model for target-concentration controlled infusion of vancomycin in critically ill patients

Clin Exp Pharmacol Physiol. 2021 Oct 1. doi: 10.1111/1440-1681.13597. Online ahead of print.

ABSTRACT

The aim of this prospective study was to construct a new pharmacokinetic model of vancomycin for target-concentration controlled infusion (TCI). As the first loading dose, 25 mg/kg of vancomycin was administered during 60-90 min. Arterial blood samples were obtained at pre-set intervals to measure the serum concentrations of vancomycin. Population pharmacokinetic analysis was performed using the NONMEM software (ICON Development Solutions, Dublin, Ireland). In total, 197 serum concentration measurements from 22 patients were used to characterize the pharmacokinetics of vancomycin. A three-compartment mammillary model best described the pharmacokinetics of vancomycin in critically ill patients. The ideal body weight was a significant covariate for the central and slow peripheral volume of distribution. The weight and age converted to categorical variables at a cut-off of 65 years were a significant covariate for the clearance. Based on the results of stochastic simulation, the TCI method maintained the therapeutic concentration range for the longest duration. In addition, assuming that vancomycin was administered by the TCI method for 7 days, the dose was reduced by about 15% compared with the standard administration methods. The daily area under the curve values were maintained between 500 mg·h/L and 600 mg·h/L. TCI has the potential to become a new infusion method for patient-tailored dosing in critically ill patients. To administer vancomycin via TCI in clinical practice, the newly constructed pharmacokinetic model should undergo proper external validation.

PMID:34596258 | DOI:10.1111/1440-1681.13597

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Remdesivir treatment in hospitalized patients with COVID-19: a comparative analysis of in-hospital all-cause mortality in a large multi-center observational cohort

Clin Infect Dis. 2021 Oct 1:ciab875. doi: 10.1093/cid/ciab875. Online ahead of print.

ABSTRACT

BACKGROUND: Remdesivir (RDV) improved clinical outcomes among hospitalized COVID-19 patients in randomized trials, but data from clinical practice are limited.

METHODS: We examined survival outcomes for US patients hospitalized with COVID-19 between Aug-Nov 2020 and treated with RDV within two-days of hospitalization vs. those not receiving RDV during their hospitalization using the Premier Healthcare Database. Preferential within-hospital propensity score matching with replacement was used. Additionally, patients were also matched on baseline oxygenation level (no supplemental oxygen charges (NSO), low-flow oxygen (LFO), high-flow oxygen/non-invasive ventilation (HFO/NIV) and invasive mechanical ventilation/ECMO (IMV/ECMO) and two-month admission window and excluded if discharged within 3-days of admission (to exclude anticipated discharges/transfers within 72-hrs consistent with ACTT-1 study). Cox Proportional Hazards models were used to assess time to 14-/28-day mortality overall and for patients on NSO, LFO, HFO/NIV and IMV/ECMO.

RESULTS: 28,855 RDV patients were matched to 16,687 unique non-RDV patients. Overall, 10.6% and 15.4% RDV patients died within 14- and 28-days, respectively compared with 15.4% and 19.1% non-RDV patients. Overall, RDV was associated with a reduction in mortality at 14-days (HR[95% CI]: 0.76[0.70-0.83]) and 28-days (0.89[0.82-0.96]). This mortality benefit was also seen for NSO, LFO and IMV/ECMO at 14-days (NSO:0.69[0.57-0.83], LFO:0.68[0.80-0.77], IMV/ECMO:0.70[0.58-0.84]) and 28-days (NSO:0.80[0.68-0.94], LFO:0.77[0.68-0.86], IMV/ECMO:0.81[0.69-0.94]). Additionally, HFO/NIV RDV group had a lower risk of mortality at 14-days (0.81[0.70-0.93]) but no statistical significance at 28-days.

CONCLUSIONS: RDV initiated upon hospital admission was associated with improved survival among COVID-19 patients. Our findings complement ACTT-1 and support RDV as a foundational treatment for hospitalized COVID-19 patients.

PMID:34596223 | DOI:10.1093/cid/ciab875