Tag: nevin manimala

BMJ Open Respir Res. 2024 Apr 4;11(1):e002238. doi: 10.1136/bmjresp-2023-002238.

ABSTRACT

BACKGROUND: We assessed the effectiveness of sotrovimab vs no early COVID-19 treatment in highest-risk COVID-19 patients during Omicron predominance.

METHODS: Retrospective cohort study using the Discover dataset in North West London. Included patients were non-hospitalised, aged ≥12 years and met ≥1 National Health Service highest-risk criterion for sotrovimab treatment. We used Cox proportional hazards models to compare HRs of 28-day COVID-19-related hospitalisation/death between highest-risk sotrovimab-treated and untreated patients. Age, renal disease and Omicron subvariant subgroup analyses were performed.

RESULTS: We included 599 sotrovimab-treated patients and 5191 untreated patients. Compared with untreated patients, the risk of COVID-19 hospitalisation/death (HR 0.50, 95% CI 0.24, 1.06; p=0.07) and the risk of COVID-19 hospitalisation (HR 0.43, 95% CI 0.18, 1.00; p=0.051) were both lower in the sotrovimab-treated group; however, statistical significance was not reached. In the ≥65 years and renal disease subgroups, sotrovimab was associated with a significantly reduced risk of COVID-19 hospitalisation, by 89% (HR 0.11, 95% CI 0.02, 0.82; p=0.03) and 82% (HR 0.18, 95% CI 0.05, 0.62; p=0.007), respectively.

CONCLUSIONS: Risk of COVID-19 hospitalisation in sotrovimab-treated patients aged ≥65 years and with renal disease was significantly lower compared with untreated patients. Overall, risk of hospitalisation was also lower for sotrovimab-treated patients, but statistical significance was not reached.

PMID:38575338 | DOI:10.1136/bmjresp-2023-002238

Aging (Albany NY). 2024 Apr 3;16. doi: 10.18632/aging.205711. Online ahead of print.

ABSTRACT

BACKGROUND: COVID-19 pandemic poses a heavy burden on public health and accounts for substantial mortality and morbidity. Proteins are building blocks of life, but specific proteins causally related to COVID-19, healthspan and lifespan have not been systematically examined.

METHODS: We conducted a Mendelian randomization study to assess the effects of 1,361 plasma proteins on COVID-19, healthspan and lifespan, using large GWAS of severe COVID-19 (up to 13,769 cases and 1,072,442 controls), COVID-19 hospitalization (32,519 cases and 2,062,805 controls) and SARS-COV2 infection (122,616 cases and 2,475,240 controls), healthspan (n = 300,477) and parental lifespan (~0.8 million of European ancestry).

RESULTS: We identified 35, 43, and 63 proteins for severe COVID, COVID-19 hospitalization, and SARS-COV2 infection, and 4, 32, and 19 proteins for healthspan, father’s attained age, and mother’s attained age. In addition to some proteins reported previously, such as SFTPD related to severe COVID-19, we identified novel proteins involved in inflammation and immunity (such as ICAM-2 and ICAM-5 which affect COVID-19 risk, CXCL9, HLA-DRA and LILRB4 for healthspan and lifespan), apoptosis (such as FGFR2 and ERBB4 which affect COVID-19 risk and FOXO3 which affect lifespan) and metabolism (such as PCSK9 which lowers lifespan). We found 2, 2 and 3 proteins shared between COVID-19 and healthspan/lifespan, such as CXADR and LEFTY2, shared between severe COVID-19 and healthspan/lifespan. Three proteins affecting COVID-19 and seven proteins affecting healthspan/lifespan are targeted by existing drugs.

CONCLUSIONS: Our study provided novel insights into protein targets affecting COVID-19, healthspan and lifespan, with implications for developing new treatment and drug repurposing.

PMID:38575325 | DOI:10.18632/aging.205711

AJNR Am J Neuroradiol. 2024 Apr 4:ajnr.A8268. doi: 10.3174/ajnr.A8268. Online ahead of print.

ABSTRACT

BACKGROUND: The effective treatment for acute ischemic stroke (AIS) patients with cervical internal carotid pseudo-occlusion (cICA-PO) requires comprehensive research on the safety and outcomes of endovascular thrombectomy (EVT). However, there is limited data available, highlighting the need for further research to ensure better treatment strategies and improve the quality of care for these patients.

PURPOSE: This study aims to assess the management and outcomes in this population group compared to patients with true carotid occlusion.

DATA SOURCES: Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus from data base inception to November 2023.

STUDY SELECTION: The size of the included studies ranged from 16 patients to 146 patients. Through the 4 full-text articles, a total of 259 patients were collected. We compared outcomes between patients with cICA-PO compared to patients with true carotid occlusions undergoing EVT due to AIS. We excluded studies with patients with carotid pseudo-occlusion without stroke, review articles, duplicate studies, overlapped data that included the same patients presented in another included study, case reports, case series with fewer than 5 patients, and meeting abstracts that did not contain the outcomes of interest. We did not pose any limitations regarding sample size or patients’ characteristics.

DATA ANALYSIS: We utilized the R statistical software (V.4.3.1; R package meta, R Foundation for Statistical Computing, Vienna, Austria) to conduct the analysis of all the data obtained. We calculated the odds ratio (OR) for binary variables, and the corresponding 95% confidence interval (CI). To synthesize the data, random-effect models, as well as forest plots were generated to visually represent the synthesis of the data. Additionally, we assessed heterogeneity using Cochran’s Q and I² tests. A P-value less than 0.05 for the Q statistic or I² more than 50% suggests significant heterogeneity. Based on a small number of studies (less than 10), the assessment of publication bias could not be reliably performed.

DATA SYNTHESIS: This meta-analysis encompassed data from 4 studies. Patients with cICA-PO and AIS who underwent EVT (n = 135) exhibited lower rates of functional independence (OR 0.35, 95% CI 0.20-0.61, p= <0.001) compared to patients with true occlusions (n = 103), as well as successful recanalization rates (OR 0.39, 95% CI 0.20-0.74, p=0.004). In addition, the cICA-PO group experienced higher mortality and sICH compared to the group with true carotid occlusions (OR 2.62, 95% CI 0.21-7.24, and OR 2.23, 95% CI 1.00-4.95, p= 0.049, respectively).

LIMITATIONS: Individual patient data was not available. Studies were a retrospective design and some of the studies had small sample sizes. The included studies in our metaanalysis did not exclude patients with tandem occlusions which might influence the results of the comparison.

CONCLUSIONS: As compared to patients with true carotid occlusion, the cICA-PO group with AIS undergoing EVT presented poor outcomes with lower functional independence and successful recanalization, as well as higher sICH and mortality rates.

PMID:38575320 | DOI:10.3174/ajnr.A8268

Aging (Albany NY). 2024 Apr 3;16. doi: 10.18632/aging.205714. Online ahead of print.

ABSTRACT

PURPOSE: The aim of this study was to investigate whether young patients with endometrial carcinoma can preserve adnexa and lymph nodes to improve their quality of life without compromising their prognosis.

METHODS: A total of 319 patients with type I endometrial carcinoma (high or moderate differentiation and less than 1/2 myometrial invasion) hospitalized in the First Affiliated Hospital of Zhengzhou University from May 2012 to July 2021 were included. The patients were divided into four groups: high differentiation without myometrial invasion group (G1MI-), high differentiation with superficial myometrial invasion group (G1MI+), moderate differentiation without myometrial invasion group (G2MI-), and moderate differentiation with superficial myometrial invasion group (G2MI+). Logistic regression analysis was conducted to identify risk factors for extra-uterine involvement. Kaplan-Meier method was used to draw the survival curve to compare the prognosis in subgroups and rates of extra-uterine involvement were also compared using Chi-square test or Fisher’s exact test.

RESULTS: Multivariable logistic regression revealed that differentiation (HR = 14.590, 95%CI = 1.778-119.754, p = 0.013) and myometrial invasion (HR = 10.732, 95%CI = 0.912-92.780, p = 0.037) were the independent risk factors for extra-uterine involvement. The overall difference was statistically significant (p < 0.001). In the subgroups analysis, both adnexal metastasis and lymph node metastasis were statistically significant in the G2MI+ group compared with G1MI- (p = 0.007, p = 0.008). There were no significant differences in the overall survival (OS) rate and progression free survival (PFS) rate among the four subgroups (p > 0.05).

CONCLUSIONS: Surgery with adnexal preservation and without systematic lymphadenectomy could be employed for the patients who are high differentiation with less than 1/2 myometrial invasion or moderate differentiation without myometrial invasion, but not recommended to the patients with moderate differentiation and superficial myometrial invasion.

PMID:38575312 | DOI:10.18632/aging.205714

BMJ Qual Saf. 2024 Apr 4:bmjqs-2023-016112. doi: 10.1136/bmjqs-2023-016112. Online ahead of print.

ABSTRACT

Mixed methods research is a popular approach used to understand persistent and complex problems related to quality and safety, such as reasons why interventions are not implemented as intended or explaining differential outcomes. However, the quality and rigour of mixed methods research proposals and publications often miss opportunities for integration, which is the core of mixed methods. Achieving integration remains challenging, and failing to integrate reduces the benefits of a mixed methods approach. Therefore, the purpose of this article is to guide quality and safety researchers in planning and designing a mixed methods study that facilitates integration. We highlight how meaningful integration in mixed methods research can be achieved by centring integration at the following levels: research question, design, methods, results and reporting and interpretation levels. A holistic view of integration through all these levels will enable researchers to provide better answers to complex problems and thereby contribute to improvement of safety and quality of care.

PMID:38575310 | DOI:10.1136/bmjqs-2023-016112

Inj Prev. 2024 Apr 4:ip-2023-044959. doi: 10.1136/ip-2023-044959. Online ahead of print.

ABSTRACT

INTRODUCTION: In the USA each year, there are approximately 3400 sudden unexpected infant (<1 year of age) deaths (SUID) which occur without an obvious cause before an investigation. SUID includes the causes of death (COD) undetermined/unknown, sleep-related suffocation/asphyxia and sudden infant death syndrome (SIDS); these are often called SUID subtypes. Three common ways SUID subtypes are grouped (SUID subtype groups) include International Classification of Diseases (ICD) Codes, SUID Case Registry Categories or Child Death Review (CDR)-Assigned Causes. These groups are often used to monitor SUID trends and characteristics at the local, state and national levels. We describe and compare the characteristics of these three SUID subtype groups.

DISCUSSION: SUID subtype groups are distinct and not directly interchangeable. They vary in purpose, strengths, limitations, uses, history, data years available, population coverage, assigning entity, guidance documentation and information available to assign subtypes.

CONCLUSION: Making informed decisions about which SUID subtype group to use is important for reporting statistics, increasing knowledge of SUID epidemiology and informing prevention strategies.

PMID:38575302 | DOI:10.1136/ip-2023-044959

J Nucl Med. 2024 Apr 4:jnumed.123.266188. doi: 10.2967/jnumed.123.266188. Online ahead of print.

ABSTRACT

Amyloid-β (Aβ) accumulation in Alzheimer disease (AD) is typically measured using SUV ratio and the centiloid (CL) scale. The low spatial resolution of PET images is known to degrade quantitative metrics because of the partial-volume effect. This article examines the impact of spatial resolution, as determined by the reconstruction configuration, on the Aβ PET quantitation in both cross-sectional and longitudinal data. Methods: The cross-sectional study involved 89 subjects with 20-min [¹⁸F]florbetapir scans generated on an mCT (44 Aβ-negative [Aβ-], 45 Aβ-positive [Aβ+]) using 69 reconstruction configurations, which varied in number of iteration updates, point-spread function, time-of-flight, and postreconstruction smoothing. The subjects were classified as Aβ- or Aβ+ visually. For each reconstruction, Aβ CL was calculated using CapAIBL, and the spatial resolution was calculated as full width at half maximum (FWHM) using the barrel phantom method. The change in CLs and the effect size of the difference in CLs between Aβ- and Aβ+ groups with FWHM were examined. The longitudinal study involved 79 subjects (46 Aβ-, 33 Aβ+) with three 20-min [¹⁸F]flutemetamol scans generated on an mCT. The subjects were classified as Aβ- or Aβ+ using a cutoff CL of 20. All scans were reconstructed using low-, medium-, and high-resolution configurations, and Aβ CLs were calculated using CapAIBL. Since linear Aβ accumulation was assumed over a 10-y interval, for each reconstruction configuration, Aβ accumulation rate differences (ARDs) between the second and first periods were calculated for all subjects. Zero ARD was used as a consistency metric. The number of Aβ accumulators was also used to compare the sensitivity of CL across reconstruction configurations. Results: In the cross-sectional study, CLs in both the Aβ- and the Aβ+ groups were impacted by the FWHM of the reconstruction method. Without postreconstruction smoothing, Aβ- CLs increased for a FWHM of 4.5 mm or more, whereas Aβ+ CLs decreased across the FWHM range. High-resolution reconstructions provided the best statistical separation between groups. In the longitudinal study, the median ARD of low-resolution reconstructed data for the Aβ- group was greater than zero whereas the ARDs of higher-resolution reconstructions were not significantly different from zero, indicating more consistent rate estimates in the higher-resolution reconstructions. Higher-resolution reconstructions identified 10 additional Aβ accumulators in the Aβ- group, resulting in a 22% increased group size compared with the low-resolution reconstructions. Higher-resolution reconstructions reduced the average CLs of the negative group by 12 points. Conclusion: High-resolution PET reconstructions, inherently less impacted by partial-volume effect, may improve Aβ PET quantitation in both cross-sectional and longitudinal data. In the cross-sectional analysis, separation of CLs between Aβ- and Aβ+ cohorts increased with spatial resolution. Higher-resolution reconstructions also exhibited both improved consistency and improved sensitivity in measures of Aβ accumulation. These features suggest that higher-resolution reconstructions may be advantageous in early-stage AD therapies.

PMID:38575189 | DOI:10.2967/jnumed.123.266188

Can J Surg. 2024 Apr 4;67(2):E158-E164. doi: 10.1503/cjs.006422. Print 2024 Jan-Feb.

ABSTRACT

BACKGROUND: The use of intraoperative diuretics, such as furosemide or mannitol, during kidney transplantation has been suggested to reduce the rate of delayed graft function (DGF). The evidence base for this is sparse, however, and there is substantial variation in practice. We sought to evaluate whether the use of intraoperative diuretics during kidney transplantation translated into a reduction in DGF.

METHODS: We conducted a cohort study evaluating the use of furosemide or mannitol given intraoperatively before kidney reperfusion compared with control (no diuretic). Adult patients receiving a kidney transplant for end-stage renal disease were allocated to receive furosemide, mannitol, or no diuretic. The primary outcome was DGF; secondary outcomes were graft function at 30 days and perioperative changes in potassium levels. Descriptive and comparative statistics were used where appropriate.

RESULTS: A total of 162 patients who received a kidney transplant from a deceased donor (either donation after neurologic determination of death or donation after circulatory death) were included over a 2-year period, with no significant between-group differences. There was no significant difference in DGF rates between the furosemide, mannitol, and control groups. When the furosemide and mannitol groups were pooled (any diuretic use) and compared with the control group, however, there was a significant improvement in the odds that patients would be free of DGF (odds ratio 2.10, 95% confidence interval 1.06-4.16, 26% v. 44%, p = 0.03). There were no significant differences noted in any secondary outcomes.

CONCLUSION: This study suggests the use of an intraoperative diuretic (furosemide or mannitol) may result in a reduction in DGF in patients undergoing kidney transplantation. Further study in the form of a randomized controlled trial is warranted.

PMID:38575180 | DOI:10.1503/cjs.006422

Neurospine. 2024 Apr 4. doi: 10.14245/ns.2448024.012. Online ahead of print.

ABSTRACT

OBJECTIVE: To demonstrate the non-inferiority of the novel hemostatic agent, Hemofence® (BMI Korea Co. Ltd., Jeju Korea, thrombin cross-linked sodium hyaluronate gel matrix) compared to the established agent, Floseal Hemostatic Matrix (Baxter, thrombin-gelatin matrix) in achieving hemostasis for spinal surgeries, with secondary objectives to assess additional efficacy and safety.

METHODS: This clinical trial was a multicenter, randomized, subject-blinded, active-controlled, parallel-group, phase 3 study. Investigational drugs were administered to the first and second bleeding sites of each participant (or only to the first site if a second site was absent), evaluating hemostasis success rate within 10 minutes and the time to achieve hemostasis. Subsequent visits were conducted for safety assessments. For non-inferiority test, a 97.5% one-sided confidence interval was used; the test group was deemed non-inferior if the lower limit exceeded -10%.

RESULTS: This trial showed a 97.10% success rate in the test group and 96.05% in the control group for primary efficacy. The 95% confidence interval (-4.90%, 7.44%) confirmed the test drug’s non-inferiority. Time to hemostasis showed no significant difference between groups. All adverse events, adverse drug reactions, and serious adverse events were statistically similar between groups (p=1.0000, p=0.2427, and p=0.9663, respectively).

CONCLUSION: A novel hemostatic agent, Hemofence®, demonstrated an efficacy and safety profile comparable to that of Floseal.

PMID:38575113 | DOI:10.14245/ns.2448024.012

Gene. 2024 Apr 2:148426. doi: 10.1016/j.gene.2024.148426. Online ahead of print.

ABSTRACT

Since late 2019, COVID-19 has significantly impacted the world. Understanding the evolution of SARS-CoV-2 is crucial for protecting against future infectious pathogens. In this study, we conducted a comprehensive chronological analysis of SARS-CoV-2 evolution by examining mutation prevalence from the source countries of VOCs: United Kingdom, India, Brazil, South Africa, plus two countries: United States, Russia, utilizing genomic sequences from GISAID. Our methodological approach involved large-scale genomic sequence alignment using MAFFT, Python-based data processing on a high-performance computing platform, and advanced statistical methods the Maximal Information Coefficient (MIC), and also Long Short-Term Memory (LSTM) models for correlation analysis. Our findings elucidate the dynamics of SARS-CoV-2 evolution, highlighting the virus’s changing behaviour over various pandemic stages. Key results include the discovery of three temporal mutation patterns-lineage distinct, long-span, and competitive mutations-with varying levels of impact on the virus. Notably, we observed a convergence of advantageous mutations in the spike protein, especially in the later stages of the pandemic, indicating a substantial evolutionary pressure on the virus. One of the most significant revelations is the predominant role of natural immunity over vaccination-induced immunity in driving these evolutionary changes. This emphasizes the critical need for regular vaccine updates to maintain efficacy against evolving strains. In conclusion, our study not only sheds light on the evolutionary trajectory of SARS-CoV-2 but also underscores the urgency for robust, continuous global data collection and sharing. It highlights the necessity for rapid adaptations in medical countermeasures, including vaccine development, to stay ahead of pathogen evolution. This research provides valuable insights for future pandemic preparedness and response strategies.

PMID:38575101 | DOI:10.1016/j.gene.2024.148426