Tag: pubmed

Drug Saf. 2023 Oct 7. doi: 10.1007/s40264-023-01353-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Individual case reports are the main asset in pharmacovigilance signal management. Signal validation is the first stage after signal detection and aims to determine if there is sufficient evidence to justify further assessment. Throughout signal management, a prioritization of signals is continually made. Routinely collected health data can provide relevant contextual information but are primarily used at a later stage in pharmacoepidemiological studies to assess communicated signals.

OBJECTIVE: The aim of this study was to examine the feasibility and utility of analysing routine health data from a multinational distributed network to support signal validation and prioritization and to reflect on key user requirements for these analyses to become an integral part of this process.

METHODS: Statistical signal detection was performed in VigiBase, the WHO global database of individual case safety reports, targeting generic manufacturer drugs and 16 prespecified adverse events. During a 5-day study-a-thon, signal validation and prioritization were performed using information from VigiBase, regulatory documents and the scientific literature alongside descriptive analyses of routine health data from 10 partners of the European Health Data and Evidence Network (EHDEN). Databases included in the study were from the UK, Spain, Norway, the Netherlands and Serbia, capturing records from primary care and/or hospitals.

RESULTS: Ninety-five statistical signals were subjected to signal validation, of which eight were considered for descriptive analyses in the routine health data. Design, execution and interpretation of results from these analyses took up to a few hours for each signal (of which 15-60 minutes were for execution) and informed decisions for five out of eight signals. The impact of insights from the routine health data varied and included possible alternative explanations, potential public health and clinical impact and feasibility of follow-up pharmacoepidemiological studies. Three signals were selected for signal assessment, two of these decisions were supported by insights from the routine health data. Standardization of analytical code, availability of adverse event phenotypes including bridges between different source vocabularies, and governance around the access and use of routine health data were identified as important aspects for future development.

CONCLUSIONS: Analyses of routine health data from a distributed network to support signal validation and prioritization are feasible in the given time limits and can inform decision making. The cost-benefit of integrating these analyses at this stage of signal management requires further research.

PMID:37804398 | DOI:10.1007/s40264-023-01353-w

J Comput Aided Mol Des. 2023 Oct 7. doi: 10.1007/s10822-023-00536-y. Online ahead of print.

ABSTRACT

QSAR models capable of predicting biological, toxicity, and pharmacokinetic properties were widely used to search lead bioactive molecules in chemical databases. The dataset’s preparation to build these models has a strong influence on the quality of the generated models, and sampling requires that the original dataset be divided into training (for model training) and test (for statistical evaluation) sets. This sampling can be done randomly or rationally, but the rational division is superior. In this paper, we present MASSA, a Python tool that can be used to automatically sample datasets by exploring the biological, physicochemical, and structural spaces of molecules using PCA, HCA, and K-modes. The proposed algorithm is very useful when the variables used for QSAR are not available or to construct multiple QSAR models with the same training and test sets, producing models with lower variability and better values for validation metrics. These results were obtained even when the descriptors used in the QSAR/QSPR were different from those used in the separation of training and test sets, indicating that this tool can be used to build models for more than one QSAR/QSPR technique. Finally, this tool also generates useful graphical representations that can provide insights into the data.

PMID:37804393 | DOI:10.1007/s10822-023-00536-y

Trop Anim Health Prod. 2023 Oct 7;55(6):352. doi: 10.1007/s11250-023-03736-8.

ABSTRACT

The current cross-sectional study aimed to determine the seroprevalence of Leptospira infection in bovine dairy farms in the Telangana state of India, as well as the associated risk factors, in order to implement effective preventive measures for disease control. A total of 469 blood samples were collected from 67 herds/farms in different areas, covering 20 administrative districts in the state. These samples consisted of 253 from cattle and 216 from buffaloes. Questionnaires were used to collect data on host and epidemiological factors. The collected sera were tested using the gold standard serological test, the Microscopic Agglutination Test (MAT), which employed a panel of 18 reference serovars for Leptospira exposure. The statistical analysis of epidemiological data was carried out to identify the risk factors associated with Leptospira exposure. The overall observed seroprevalence at the animal and farm levels was 41.4% and 77.6%, respectively. The most prevalent anti-leptospiral antibodies were observed against the serogroups Icterohaemorrhagiae (32.4%), Pomona (22.2%), Javanica (19.1%), Australis (17.0%), Bataviae (15.5%), Autumnalis (12.9%), Hebdomadis (12.9%), and others, in the total reacting samples. At the animal level, the significant risk factors associated with exposure to Leptospira species were breed (p = 0.03) and health status (p = 0.03). Furthermore, the multivariate statistical analysis of farm factors revealed that farm size (p = 0.05), presence of dogs (p = 0.04) and rodents (p = 0.01) on the farm, use of fodder from wet soils (p = 0.04), and proximity to water bodies (p = 0.04) were significantly associated with exposure to Leptospira in the studied region. This study provides the first report from India highlighting the important risk factors at the herd/farm and animal level associated with Leptospira infections in cattle and buffaloes. The findings contribute to strengthening the one-health strategy by facilitating the design and planning of appropriate control measures to alleviate the burden of leptospirosis in bovines.

PMID:37804390 | DOI:10.1007/s11250-023-03736-8

Clin Exp Med. 2023 Oct 7. doi: 10.1007/s10238-023-01190-2. Online ahead of print.

ABSTRACT

PD-L1 expression is known to predict the benefits of immune checkpoint inhibitor therapy for triple-negative breast cancer (TNBC). We examined whether the PD-L1 expression evaluated in biopsy specimens accurately reflects its expression in the whole tumor. Immunohistochemistry was performed on 81 biopsy and resection specimens from patients with TNBC to determine their PD-L1 status. We found PD-L1-positive tumors in 23 (28%) biopsy specimens and primarily PD-L1-negative tumors in 58 (72%). The PD-L1 status was reevaluated in matching postoperative specimens of primarily PD-L1-negative tumors. Of them, 31% (18/58) were positive, whereas 69% (40/58) were negative. Considering the pre- and postoperative analyses, 41 (51%) patients had PD-L1-positive tumors, while 40 had PD-L1-negative tumors. We found 18 (22%) more PD-L1-positive tumors while examining the resection specimens compared to biopsies, and the difference was statistically significant (p = 0.0038). Diagnostic biopsies do not fully reflect the PD-L1 expression in TNBC. Our results suggest that a significant subset of TNBC patients may be misclassified as PD-L1-negative and disqualified from anti-PD-L1 therapy.

PMID:37804360 | DOI:10.1007/s10238-023-01190-2

Knee Surg Sports Traumatol Arthrosc. 2023 Oct 7. doi: 10.1007/s00167-023-07578-7. Online ahead of print.

ABSTRACT

PURPOSE: This study reports the five-year functional outcomes from a prospective cohort study comparing robotic-arm assisted total knee arthroplasty (RO TKA) versus conventional manual total knee arthroplasty (CO TKA).

METHODS: This prospective single-surgeon study included 120 patients with symptomatic end-stage knee arthritis undergoing primary TKA. This included 60 consecutive patients undergoing CO TKA followed by 60 consecutive patients undergoing RO TKA using a semi-automated robotic device. Study patients were reviewed at one, two, and five years after surgery and the following outcomes recorded: The University of California at Los Angeles activity-level (UCLA), Knee Society Score (KSS), Oxford Knee Score (OKS) Forgotten Joint Score (FJS), and any complications.

RESULTS: There were no statistical differences between RO TKA and CO TKA in the median UCLA score (p = N.S), median KSS (p = N.S), and median OKS (p = N.S) at five-year follow-up. RO-TKA was associated with statistically significant improvements in the FJS at one (p = 0.001), two (p = 0.003), and five (p = 0.025) years of follow-up compared with CO TKA. There was no statistical difference in the incidence of knee stiffness requiring manipulation under anesthesia between the two treatment groups (p = N.S).

CONCLUSION: Patients in both treatment groups had excellent functional outcomes with comparable patient reported outcomes at five-year follow-up. RO TKA was associated with statistically significant improvements in the FJS compared with CO TKA, but these differences did not reach the minimal clinically important difference at any follow-up interval. There was no overall difference in complications between the two treatment groups at five-year follow-up.

LEVEL OF EVIDENCE: II (Prospective cohort study).

PMID:37804346 | DOI:10.1007/s00167-023-07578-7

World J Urol. 2023 Oct 7. doi: 10.1007/s00345-023-04623-5. Online ahead of print.

ABSTRACT

PURPOSE: To compare the effects of different preoperative antibiotic prophylaxis (ABP) regimens on the incidence of sepsis after percutaneous nephrolithotomy (PCNL) in patients with negative urine culture.

METHODS: A single-center, randomized controlled trial (June 2022-December 2023) included 120 patients with negative preoperative urine cultures for upper urinary tract stones who underwent PCNL (chictr.org.cn; ChiCTR2200059047). The experimental group and the control group were respectively given different levofloxacin-based preoperative ABP regimes, including 3 days before surgery and no ABP before surgery. Both groups were given a dose of antibiotics before the operation. The primary outcome was differences in the incidence of postoperative sepsis.

RESULTS: A total of 120 subjects were included, including 60 patients in the experimental group and 60 patients in the control group. The baseline characteristics of the two groups were comparable and intraoperative characteristics also did not differ. The sepsis rate was not statistically different between the experimental and control groups (13.3% vs.13.3%, P = 1.0). A multivariate logistic regression analysis revealed that body mass index (BMI) (OR = 1.3; 95% CI = 1.1-1.6; P = 0.003) and operating time (OR = 1.1; 95% CI = 1.0-1.1; P = 0.012) were independent risk factors of sepsis.

CONCLUSION: Our study showed that prophylactic antibiotic administration for 3 days before surgery did not reduce the incidence of postoperative sepsis in patients with negative urine cultures undergoing PCNL. For this subset of patients, we recommend that a single dose of antibiotics be given prior to the commencement of surgery seems adequate.

PMID:37804339 | DOI:10.1007/s00345-023-04623-5

Acta Diabetol. 2023 Oct 7. doi: 10.1007/s00592-023-02190-0. Online ahead of print.

ABSTRACT

AIMS: Observational studies have reported that autoimmune diseases are associated with gestational diabetes mellitus (GDM), but the causality is unknown. The study aimed to evaluate the potential causal effect of autoimmune diseases on GDM.

METHODS: A two-sample Mendelian randomization (MR) study was designed using the summary statistics of GDM (123,579 individuals) and three common autoimmune diseases, including inflammatory bowel disease (IBD, 59,957 individuals), rheumatoid arthritis (RA, 80,799 individuals) and systemic lupus erythematosus (SLE, 14,267 individuals), from the genome-wide association study (GWAS). The fixed-effects inverse variance weighted (IVW) was used to deduce the causal association between autoimmune diseases and GDM, and sensitivity analyses were further performed.

RESULTS: The inverse variance weighting (IVW) method showed that RA and SLE increased the risk of GDM (RA: OR = 1.076, 95%CI = 1.033-1.122, P = 4.649E-04; SLE: OR = 1.025, 95%CI = 1.001-1.049, P = 0.044). But there were no any associations of IBD with GDM (P > 0.05). No significant horizontal pleiotropy was found by MR Egger regression (IBD: P for intercept = 0.905; RA: P for intercept = 0.103; SLE = P for intercept = 0.608).

CONCLUSION: This two-sample MR study found that both SLE and RA are positively associated with the risk of GDM. Our findings provide help for the future prevention and treatment of GDM to reduce associated maternal and fetal complications. However, more research is needed to obviate the role of the GC and the HCQ to ensure this relationship is causal.

PMID:37804336 | DOI:10.1007/s00592-023-02190-0

JACC Heart Fail. 2023 Sep 20:S2213-1779(23)00520-6. doi: 10.1016/j.jchf.2023.07.028. Online ahead of print.

ABSTRACT

BACKGROUND: Peripartum cardiomyopathy (PPCM) remains an important cause of maternal morbidity and mortality globally. The pathophysiology remains incompletely understood, and the diagnosis is often missed or delayed.

OBJECTIVES: This study explored the serum proteome profile of patients with newly diagnosed PPCM, as compared with matched healthy postpartum mothers, to unravel novel protein biomarkers that would further an understanding of the pathogenesis of PPCM and improve diagnostic precision.

METHODS: Study investigators performed untargeted serum proteome profiling using data-independent acquisition-based label-free quantitative liquid chromatography-tandem mass spectrometry on 84 patients with PPCM, as compared with 29 postpartum healthy control subjects (HCs). Significant changes in protein intensities were determined with nonpaired Student’s t-tests and were further classified by using the Boruta algorithm. The proteins’ diagnostic performance was evaluated by area under the curve (AUC) and validated using the 10-fold cross-validation.

RESULTS: Patients with PPCM presented with a mean (± SD) left ventricular ejection fraction of 33.5 ± 9.3% vs 57.0 ± 8.8% in HCs (P < 0.001). Study investigators identified 15 differentially up-regulated and 14 down-regulated proteins in patients with PPCM compared with HCs. Seven of these proteins were recognized as significant by the Boruta algorithm. The combination of adiponectin, quiescin sulfhydryl oxidase 1, inter-α-trypsin inhibitor heavy chain, and N-terminal pro-B-type natriuretic peptide had the best diagnostic precision (AUC: 0.90; 95% CI: 0.84-0.96) to distinguish patients with PPCM from HCs.

CONCLUSIONS: Salient biologic themes related to immune response proteins, inflammation, fibrosis, angiogenesis, apoptosis, and coagulation were predominant in patients with PPCM compared with HCs. These newly identified proteins warrant further evaluation to establish their role in the pathogenesis of PPCM and potential use as diagnostic markers.

PMID:37804308 | DOI:10.1016/j.jchf.2023.07.028

J Adolesc Health. 2023 Oct 5:S1054-139X(23)00415-9. doi: 10.1016/j.jadohealth.2023.08.006. Online ahead of print.

ABSTRACT

PURPOSE: This paper uses data from a 3-arm Cluster Randomized Control Trial, Suubi4Her (N = 1260; 14-17-year-old school-going girls) to (1) assess the relationship between peer pressure and adolescent risk-taking behaviors; and (2) test the mediating effect of peer pressure on an intervention on adolescent risk-taking behaviors.

METHODS: Students in the southwestern region of Uganda were assigned to three study arms: control (n = 16 schools, n = 408 students) receiving usual care comprising of sexual and reproductive health curriculum; and two active treatment arms: Treatment 1 (n = 16 schools, n = 471 students) received everything the control arm received plus a savings led intervention. Treatment 2 (n = 15 schools, n = 381 students) received everything the control and treatment arms received plus a family strengthening intervention. We used multilevel models to assess the relationship between peer pressure and risk-taking behaviors. We ran structural equation models for mediation analysis.

RESULTS: Using baseline data, we found that direct peer pressure was significantly associated with substance use risk behaviors, (β = 0.044, 95% CI = 0.008, 0.079). We also found a statistically significant effect of the intervention on acquiring STIs through the mediating effect of sexual risk-taking significant (β = -0.025, 95% CI: -0.049, -0.001, p = .045) and total indirect (β = -0.042, 95% CI: -0.081, -0.002, p = .037) effects. Also, there was a significant mediation effect of the intervention on substance use through peer pressure (β = -0.030, 95% CI: -0.057, -0.002, p = .033).

DISCUSSION: Overall, the study points to the role of peer pressure on adolescent girls’ risk-taking behaviors; and a need to address peer pressure at an early stage.

PMID:37804302 | DOI:10.1016/j.jadohealth.2023.08.006

Cytotherapy. 2023 Oct 7:S1465-3249(23)01050-2. doi: 10.1016/j.jcyt.2023.09.002. Online ahead of print.

ABSTRACT

BACKGROUND AIMS: Exosome therapy for traumatic spinal cord injury (TSCI) is a current research hotspot, but its therapeutic effect and the best source of stem cells for exosomes are unclear.

METHODS: The Web of Science, PubMed, Embase, Cochrane, and Scopus databases were searched from inception to March 28, 2023. Literature screening, data extraction and risk of bias assessment were performed independently by two investigators.

RESULTS: A total of 40 studies were included for data analysis. The findings of our traditional meta-analysis indicate that exosomes derived from stem cells significantly improve the motor function of TSCI at various time points (1 week: weighted mean difference [WMD] = 1.58, 95% confidence interval [CI] 0.87-2.30] 2 weeks: WMD = 3.12, 95% CI 2.64-3.61; 3 weeks: WMD = 4.44, 95% CI 3.27-5.60; 4 weeks: WMD = 4.54, 95% CI 3.42-5.66). Four kinds of stem cell-derived exosomes have been studied: bone marrow mesenchymal stem cells, adipose mesenchymal stem cells, umbilical cord mesenchymal stem cells and neural stem cells. The results of the network meta-analysis showed that there was no significant statistical difference in the therapeutic effect among the exosomes derived from four kinds of stem cells at different treatment time points. Although exosomes derived from bone marrow mesenchymal stem cells are the current research focus, exosomes derived from neural stem cells have the most therapeutic potential and should become the focus of future attention.

CONCLUSIONS: The exosomes derived from stem cells can significantly improve the motor function of TSCI rats, and the exosomes derived from neural stem cells have the most therapeutic potential. However, the lower evidence quality of animal studies limits the reliability of experimental results, emphasizing the need for more high-quality, direct comparative studies to explore the therapeutic efficacy of exosomes and the best source of stem cells.

PMID:37804282 | DOI:10.1016/j.jcyt.2023.09.002