Tag: statistics

Drugs R D. 2023 Sep 13. doi: 10.1007/s40268-023-00438-2. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: N-terminal pro-B-type natriuretic peptide (NT-proBNP) and soluble interleukin 1 receptor-like 1 ST2 (sST2) are biomarkers used to grade heart failure with reduced ejection fraction (HFrEF) severity. Both are potential targets of HFrEF treatment, but the first is associated with the patient’s hemodynamic status, while the second is more indicative of the inflammatory status and of myocardial fibrosis. The aim of this study was to assess the kinetics of these biomarkers after treatment with sacubitril/valsartan in HFrEF.

METHODS: We analyzed blood samples of patients with HFrEF at baseline (before sacubitril/valsartan treatment), after 1, 2, and 3 months (respectively, after a month taking the 24/26 – 49/51 – 97/103 mg twice daily, or b.i.d., doses), and 6 months after the maximum-tolerated dose was reached (end study).

RESULTS: We obtained samples from 72 patients with HFrEF (age 64.0 ± 10.5 years, 83% males). NT-proBNP and sST2 values progressively and significantly reduced to 37% and 16%, respectively, with a greater reduction for NT-proBNP (p < 0.001). Specifically, NT-proBNP reduced from 1144 [593-2586] pg/mL to 743 [358-1524] pg/mL and sST2 from 27.3 [20.5-35.0] ng/mL to 23.1 [15.9-30.7] ng/mL, p for trend < 0.001 in both cases. The reduction of the two biomarkers over time occurred with statistically significant different kinetics: deferred for sST2 and faster for NT-proBNP. No significant changes in renal function and potassium levels were recorded.

CONCLUSION: These findings suggest that, in patients with HF, sacubitril/valsartan effects on the cardiovascular system share a double pathway: a first, hemodynamic, faster pathway and a second, non-hemodynamic anti-fibrotic, delayed one. Both likely contribute to the sacubitril/valsartan benefits in HFrEF.

PMID:37702906 | DOI:10.1007/s40268-023-00438-2

Eur Arch Paediatr Dent. 2023 Sep 13. doi: 10.1007/s40368-023-00821-2. Online ahead of print.

ABSTRACT

PURPOSE: The primary objective of the review was to assess the effectiveness of self-assembling P11-4 peptide (SAP) with or without any fluoride agents (FA) in remineralization of the White spot lesions (WSLs)/incipient carious lesions (ICLs) compared to other enamel remineralizing agents/non-intervention/placebo.

METHODS: Human RCTs published during the period from 1st January 2000-30th June 2021 were searched in the electronic bibliographic databases and scanning reference lists of articles from PubMed, Google Scholar, and The Cochrane Central Register of Controlled Trials. The Risk-of-Bias was assessed using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2) tool for all included studies. The statistical heterogeneity between studies was assessed by the Cochrane Q test and I² test. A random-effects model was used considering the variations in true effects size between the included studies. The quality of the evidence for remineralizing effectiveness of SAP/SAP + FA was done using the GRADEpro GDT software which employs GRADE.

RESULTS: Four out of eight included trials were assessed to have “high risk” of bias. Mean difference for Laser fluorescence outcome assessment method (SAP v/s FA) was – 4.89 (95% CI: – 17.35 to 7.57; p = 0. 44; I² = 89%). The combined risk ratio observed through Nyvad criteria (SAP v/s FA) was 0.12 (95% CI: 0.01-1.59; p = 0.11; I² = 71%). Mean difference for Laser fluorescence outcome assessment method (SAP + FA v/s FA) was – 11.52 (95% CI: – 14.43 to – 8.61; p = < 0.001;I² = 0%). The combined risk ratio for ICDAS outcome assessment method (SAP + FA v/s FA) was 0.27 (95% CI: 0.03-2.84; p = 0.15; I² = 53%).

CONCLUSION: Considering the results observed from the included trials we are uncertain whether SAP/SAP + FA increases/decreases the remineralizing/regeneration of WSLs/ICLs.

PMID:37702901 | DOI:10.1007/s40368-023-00821-2

Endocrine. 2023 Sep 13. doi: 10.1007/s12020-023-03507-3. Online ahead of print.

ABSTRACT

PURPOSE: Patients with locally advanced or metastatic differentiated thyroid cancer (DTC) have a variable prognosis, and the development of more effective treatment strategies is an important research topic. Overall survival (OS) is the gold standard for research endpoints in randomized controlled trials (RCTs), but observing an OS benefit requires the inclusion of a large number of patients and a long follow-up period. In this study, we aimed to investigate whether progression-free survival (PFS) could be used as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials.

MATERIALS AND METHODS: We conducted a search in the PubMed and EMBASE databases to include all RCTs of locally advanced or metastatic DTC and extracted survival data. A weighted linear regression analysis was performed to explore the correlation between PFS benefit and OS benefit by taking the logarithm of the hazard ratios (HRs) of PFS and OS for each trial with a base of 10 and weighted by the number of patients in each RCT.

RESULTS: Seven RCTs, including 1410 patients, were included. At the trial level, PFS benefit was weakly correlated with OS benefit (R² = 0.210, 95% CI: 0.000-0.811) and did not meet the statistical criteria for the surrogate endpoint.

CONCLUSION: This study does not support PFS as a surrogate endpoint for OS in locally advanced or metastatic DTC clinical trials.

TRIAL REGISTRATION: PROSPERO Identifier: CRD42022334898.

PMID:37702900 | DOI:10.1007/s12020-023-03507-3

Aging Ment Health. 2023 Sep 13:1-8. doi: 10.1080/13607863.2023.2256271. Online ahead of print.

ABSTRACT

OBJECTIVES: Compared with younger and middle-aged adults, older adults are less likely to adopt new computer technology, potentially limiting access to healthcare and many other important resources available online. This limitation could impact cognitive abilities, well-being, and mental health outcomes of older adults. The aims of the present study were to increase access to online county and healthcare resources, while also assessing the impact of technology access on cognitive functioning and multiple well-being domains.

METHODS: A pilot community collaboration provided a two-month tablet training intervention, focused on increasing digital independence via tablet navigation, resources access, and fraud and scam prevention, to 20 low-income older adult participants (75% female, M_age = 70.85). Pre- and post-test phone interviews were conducted to measure any changes in digital independence, cognitive abilities, well-being, mental health, and mindset.

RESULTS: Linear mixed effects models revealed no significant changes in outcome measures from pre- to post-test. However, we found effects of digital independence on several well-being measures, providing important information for the impact of technology access and training for low-income older adults.

CONCLUSION: This pilot intervention offers limited but promising results, inspiring further investigations that may inform public health and policy services to address barriers to access and potentially improve psychological health.

PMID:37702149 | DOI:10.1080/13607863.2023.2256271

J Magn Reson Imaging. 2023 Sep 13. doi: 10.1002/jmri.28974. Online ahead of print.

ABSTRACT

BACKGROUND: In neuroscience, accurately quantifying individual brain regions in large cohorts is a challenge. Differences in intracranial structures can suggest functional differences, but they also reflect the effects of other factors. However, there is currently no standardized method for the correction of intracranial structure measurements.

PURPOSE: To identify the optimal method to counteract the influence of total intracranial volume (TIV) and gender on the measurement of intracranial structures.

STUDY TYPE: Prospective.

POPULATION/SUBJECTS: One hundred forty-one healthy adult volunteers (70 male, mean age 21.8 ± 1.7 years).

FIELD STRENGTH/SEQUENCE: T1-weighted 3D gradient-echo sequence at 3.0 T.

ASSESSMENT: A radiologist with 5 years of work experience screened the raw images to exclude poor-quality images. Freesurfer then performed automated segmentation to obtain measurements of intracranial structures. Male-only, female-only, and TIV-matched sub-samples were created separately. Comparisons between the original data and these sub-samples were used to assess the effects of gender and TIV. Comparison the consistency between TIV-matched sample and corrected data that corrected by four methods: Proportion method, power-corrected proportion method, covariate regression method, and residual method.

STATISTICAL TESTS: Cohen’s d for examining group distribution disparities, t-tests for probing mean differences, correlation coefficients to assess the relationships between intracranial substructure measurements and TIV. Multiple comparison corrections were applied to the results.

RESULTS: The correlation coefficients between TIV and the volumes of intracranial structures ranged from 0.033 to 0.883, with an average of 0.467. Thirty significant volume differences were found among 36 structures in the original sample, while no differences were observed in the TIV-matched sample. Among the four correction methods, the residual method had highest consistency (similarity 94.4%) with the TIV-matched group.

DATA CONCLUSION: The variation in intracranial structure sizes between genders was largely attributable to TIV. The residual method offers a more accurate and effective approach for correcting the effects of TIV on intracranial structures.

EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

PMID:37702125 | DOI:10.1002/jmri.28974

Angew Chem Int Ed Engl. 2023 Sep 13:e202312830. doi: 10.1002/anie.202312830. Online ahead of print.

ABSTRACT

“The most exciting thing about my research is the freedom and flexibility that computational chemistry offers to work on any element in the periodic table… My favorite example of chemistry/science in everyday life is the way nature keeps statistical averages and Gaussian distributions.” Find out more about Rajeev Ramanan in his Introducing… Profile.

PMID:37702098 | DOI:10.1002/anie.202312830

Health Econ Policy Law. 2023 Sep 13:1-15. doi: 10.1017/S1744133123000178. Online ahead of print.

ABSTRACT

Nurse workforce shortages put healthcare systems under pressure, moving the nursing profession into the core of healthcare policymaking. In this paper, we shift the focus from workforce policy to workforce politics and highlight the political role of nurses in healthcare systems in England, Spain, Sweden, and the Netherlands. Using a comparative discursive institutionalist approach, we study how nurses are organised and represented in these four countries. We show how nurse politics plays out at the levels of representation, working conditions, career building, and by breaking with the public healthcare system. Although there are differences between the countries – with nurses in England and Spain under more pressure than in the Netherlands and Sweden – nurses are often not represented in policy discourses; not just because of institutional ignorance but also because of fragmentation of the profession itself. This institutional ignorance and lack of collective representation, we argue, requires attention to foster the role and position of nurses in contemporary healthcare systems.

PMID:37702051 | DOI:10.1017/S1744133123000178

Drug Deliv. 2023 Dec;30(1):2252999. doi: 10.1080/10717544.2023.2252999.

ABSTRACT

Subcutaneous (SC) infusion of large volumes at rapid flow rates has historically been limited by the glycosaminoglycan hyaluronan (HA), which forms a barrier to bulk fluid flow in the SC space. Recombinant human hyaluronidase PH20 (rHuPH20) depolymerizes HA, temporarily eliminating this barrier to rapid SC delivery of large volume co-administered therapeutics. Using a miniature pig model, in-line pressure and applied force to the delivery hardware were measured when subcutaneously infusing a representative macromolecule (human polyclonal immunoglobulin [Ig]), at varying concentrations and viscosities (20-200 mg/mL), co-formulated with and without rHuPH20 (2000 U/mL and 5000 U/mL). Maximal flow rate (Q_max) was calculated as the flow rate producing a statistically significant difference in mean applied force between injections administered with or without rHuPH20. There was a significant reduction in mean applied force required for SC delivery of 100 mg/mL Ig solution with 5000 U/mL rHuPH20 versus Ig solution alone. Similar significant reductions in mean applied force were observed for most Ig solution concentrations, ranging from 25-200 mg/mL when administered with or without 2000 U/mL rHuPH20. Q_max was inversely proportional to Ig solution viscosity and Q_max for solutions co-formulated with 5000 U/mL rHuPH20 was approximately double that of 2000 U/mL rHuPH20 solutions. Mathematical simulation of a hypothetical 800 mg Ig dose co-formulated with rHuPH20 showed that delivery times <30 s could be achieved across a broad range of concentrations. Addition of rHuPH20 can help overcome volume and time constraints associated with SC administration across a range of concentrations in a dose-dependent manner.

PMID:37702020 | DOI:10.1080/10717544.2023.2252999

Pediatr Pulmonol. 2023 Sep 13. doi: 10.1002/ppul.26676. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep disordered breathing (SDB) may exacerbate asthma and is a treatable comorbidity.

OBJECTIVE: To design and implement a screening process for SDB in patients hospitalized for asthma exacerbation using quality improvement (QI) methods. We sought to improve screening for SDB from zero to 60% from July 2019 to December 2020.

DESIGN/METHODS: A multidisciplinary team used QI methods to screen for SDB using the Michigan pediatric sleep questionnaire (PSQ) in patients 2-18 years hospitalized for asthma exacerbation. Key interventions included: pairing the PSQ screen with another element of routine care (the asthma risk factor screen), educating staff and physicians, engaging respiratory therapists to complete the PSQ and document scores, and modifying the electronic medical record (asthma order set and flowsheet for PSQ score documentation). A run chart tracked progress and descriptive statistics were generated.

RESULTS: There were 2067 patients admitted for asthma exacerbation during this project. The PSQ was completed for 1531 patients (74%) overall. Of screened patients, 360 (24%) had a positive PSQ; the mean age was 8.6 years. Approximately 14 months after the project began, ~90% of children admitted for asthma were being screened; subsequently, >80% of patients were being screened until May 2022. Screening with the PSQ occurred approximately 90% of the time when routine asthma risk screens were completed.

CONCLUSION: A screening process for SDB was successfully implemented and appeared feasible and sustainable. The high proportion of positive screens reinforces the importance of evaluating for SDB in the high-risk population of children requiring hospitalization for asthma exacerbation.

PMID:37701984 | DOI:10.1002/ppul.26676

J Neurophysiol. 2023 Sep 13. doi: 10.1152/jn.00248.2023. Online ahead of print.

ABSTRACT

The dynamics and interaction of spinal and suparspinal centers during locomotor adaptation remain vaguely understood. In this work, we use Hoffmann reflex measurements to investigate changes of spinal reflex gains during split-belt locomotor adaptation. We show that spinal reflex gains are dynamically modulated during split-belt locomotor adaptation. During first exposure to split-belt transitions, modulation occurs mostly on the leg ipsilateral to the speed change, and constitutes rapid suppression or facilitation of the reflex gains, followed by slow recovery to baseline. Over repeated exposure, the modulation pattern washes out. We further show that reflex gain modulation strongly correlates with correction of leg asymmetry, and cannot be explained by speed modulation solely. We argue that reflex modulation is likely of supraspinal origins, and constitutes an integral part of the neural substrate underlying split-belt locomotor adaptation.

PMID:37701940 | DOI:10.1152/jn.00248.2023