Category: Nevin Manimala

J Patient Rep Outcomes. 2023 Sep 13;7(1):92. doi: 10.1186/s41687-023-00621-8.

ABSTRACT

BACKGROUND: The COMET-ICE trial demonstrated that sotrovimab clinically and statistically significantly reduces the risk of all-cause > 24-h hospitalization or death due to any cause among patients with COVID-19 at high risk of disease progression. Patient-reported outcomes are important to capture symptom burden of COVID-19 and assess treatment effectiveness. This study investigated symptoms and their impact over the acute phase of COVID-19 infection among patients on sotrovimab versus placebo.

METHODS: Randomized (1:1), double-blind, multicenter, placebo-controlled, phase 2/3 study in 57 centers across five countries. Participants were non-hospitalized patients with symptomatic, mild-to-moderate COVID-19 and ≥ 1 baseline risk factor for disease progression (aged ≥ 55 years or ≥ 1 of the following: diabetes requiring medication, obesity, chronic kidney disease, congestive heart failure, chronic obstructive pulmonary disease, or moderate-to-severe asthma). An intravenous infusion of sotrovimab 500 mg or placebo was administered on Day 1. The FLU-PRO Plus questionnaire was administered once-daily with 24-h recall from Day 1-21, and at Day 29. Intensity and duration of COVID-19 symptoms were determined from area under the curve (AUC) and mean change in total and individual domain scores through Days 7, 14, and 21. Time to symptom alleviation was assessed.

RESULTS: In total, 1057 patients were randomized to sotrovimab (n = 528) or placebo (n = 529). At Day 7, mean decrease in FLU-PRO Plus total score (measured by AUC) was statistically significantly greater for patients on sotrovimab (-3.05 [95% confidence interval (CI) -3.27 to -2.83]) than placebo (-1.98 [95% CI -2.20 to -1.76]; difference -1.07 [95% CI -1.38 to -0.76]; p < 0.001). Significant differences were also observed at Days 14 and 21. A more rapid decline in symptom severity was observed with sotrovimab versus placebo through Week 1 and the first 21 days post-treatment. By Day 21, 41% of patients on sotrovimab and 34% on placebo reported symptom resolution. In a post-hoc analysis, median time to symptom alleviation was 4 and 6 days, respectively.

CONCLUSIONS: Sotrovimab provides significant and rapid improvements in patient-reported COVID-19 symptoms, as measured by the FLU-PRO Plus. These results further show the benefits of sotrovimab in alleviating symptoms among high-risk patients with COVID-19. Trial registration ClinicalTrials.Gov: NCT04545060 ( https://clinicaltrials.gov/ct2/show/NCT04545060 ). Date of registration: September 10, 2020 (retrospectively registered).

PMID:37702920 | DOI:10.1186/s41687-023-00621-8

J Nephrol. 2023 Sep 13. doi: 10.1007/s40620-023-01761-2. Online ahead of print.

ABSTRACT

BACKGROUND: The outcome of renal vein thrombosis, in particular as for the long-term impact on kidney function, is not fully known. We aimed to study the natural course and outcomes of patients with renal vein thrombosis, in a large, single-center cohort.

METHODS: A single-center retrospective cohort study including patients who were diagnosed with renal vein thrombosis between January 2006 and September 2021 was analyzed. The main outcomes analyzed were worsening kidney function, defined as a decrease in eGFR of at least 40% from baseline, and all-cause mortality.

RESULTS: Eighty-seven patients were included, 56.3% were female, median age was 57 years. Malignancy was the most common cause of renal vein thrombosis (60.9%), followed by post-surgery and trauma (16.1%) and nephrotic syndrome (12.6%). At initial presentation, 65.5% of the patients were asymptomatic; the main signs and symptoms were gross hematuria (20.7%), flank pain (18.4%), and flank tenderness (9.2%). During follow-up, 18 (21.4%) patients experienced worsening kidney function and 57 (65.5%) died. Multivariable analyses showed that the risk of worsening kidney function was higher in patients with nephrotic syndrome (hazard ratio [HR] 18.41; 95% confidence interval [CI], 1.57-216.04), body weight ≥ 60 kg (HR 4.82; 95% CI 1.43-16.32), and malignancy (HR 9.10; 95% CI 1.05-78.63). Symptomatic acute renal vein thrombosis was associated with a lower risk of worsening kidney function compared to asymptomatic or symptomatic chronic renal vein thrombosis (HR 0.12; 95% CI 0.01-0.96). Malignancy (HR 5.45; 95% CI 2.58-11.54), age ≥ 75 years (HR 3.44; 95% CI 1.49-7.93), and serum albumin < 3.0 g/dL (HR 2.88; 95% CI 1.65-5.05) were associated with an increased mortality risk.

CONCLUSION: Renal vein thrombosis is associated with a high rate of worsening kidney function and mortality. It is crucial to promptly identify patients at high risk and initiate early treatment to prevent negative outcomes.

PMID:37702914 | DOI:10.1007/s40620-023-01761-2

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