Category: Statistics

J Physiol Pharmacol. 2024 Jun;75(3). doi: 10.26402/jpp.2024.3.02. Epub 2024 Jul 18.

ABSTRACT

Suicide is a significant public health challenge worldwide. Statistical data confirm a strong relationship between suicidal behavior and depressive disorders (DDs), but the molecular mechanisms of these diseases are still poorly understood. A growing body of research suggests that the Klotho-mediated pathway may be a novel intracellular target for the development of suicide-related disorders (including DDs). To verify this hypothesis, the link between α-Klotho levels, Nrf2-related inflammatory status (IL-1α, IL-1β, Keap1, NFκB p65), AMPA (GluA1, GluA2, p-S831-GluA1, p-S845-GluA1) receptor subunit trafficking and AMPK (AMPKα1/2; pT172-AMPKα1) signalling pathways in the brain of suicide victims as compared to controls were investigated. Commercially available enzyme-linked immunoassay (ELISA) and Western blot analysis were performed in the hippocampus (HP) and frontal cortex (FCx) of suicide victims and matched controls. Group differences were assessed using an unpaired Student’s t-test. A statistically significant decrease in the level of α-Klotho (HP: p=0.001; FCx: p=0.012) with an increase in IL-1β (HP: p=0.0108) and IL-1α (FCx: p=0.009) concentrations were shown. These alterations were associated with increased Keap1 (FCx: p=0.023) and NF-κB-p65 (HP: p=0.039; FCx: p=0.013 nuclear fraction) protein levels. Furthermore, a significant reduction in p-S831-GluA1 (HP: p=0.029; FCx=0.002) and p-S845-GluA1 (HP: p=0.0012) proteins was observed. Similarly, the level of GluA2 (HP: p=0.011; FCx: p=0.002) and in p-T172-AMPKα1 (HP: p=0.0288; FCx: p=0.0338) protein were statistically decreased. Our findings demonstrate that a reduction in α-Klotho levels in brain structures related to mood disorders (HP, FCx) correlates with suicidal behavior. Moreover, our study provides novel insights into the molecular mechanisms underlying suicide-related disorders, highlighting the role of α-Klotho, Nrf2-related inflammatory status, AMPA receptor trafficking, and AMPK signaling pathways in the pathophysiology of suicidal behavior. These results may have implications for the development of targeted interventions for individuals at risk of suicide.

PMID:39042386 | DOI:10.26402/jpp.2024.3.02

Int J Clin Pharm. 2024 Jul 23. doi: 10.1007/s11096-024-01770-6. Online ahead of print.

ABSTRACT

BACKGROUND: Comprehensive medication management (CMM) programs optimize the effectiveness and safety of patients’ medication regimens, but CMM may be underutilized. Whether healthcare claims data can identify patients appropriate for CMM is not well-studied.

AIM: Determine the face validity of a claims-based algorithm to prioritize patients who likely need CMM.

METHOD: We used claims data to construct patient-level markers of “regimen complexity” and “high-risk for adverse effects,” which were combined to define four categories of claims-based CMM-need (very likely, likely, unlikely, very unlikely) among 180 patient records. Three clinicians independently reviewed each record to assess CMM need. We assessed concordance between the claims-based and clinician-review CMM need by calculating percent agreement as well as kappa statistic.

RESULTS: Most records identified as ‘very likely’ (90%) by claims-based markers were identified by clinician-reviewers as needing CMM. Few records within the ‘very unlikely’ group (5%) were identified by clinician-reviewers as needing CMM. Interrater agreement between CMM-based algorithm and clinician review was moderate in strength (kappa = 0.6, p < 0.001).

CONCLUSION: Claims-based pharmacy measures may offer a valid approach to prioritize patients into CMM-need groups. Further testing of this algorithm is needed prior to implementation in clinic settings.

PMID:39042353 | DOI:10.1007/s11096-024-01770-6

J Assist Reprod Genet. 2024 Jul 23. doi: 10.1007/s10815-024-03193-8. Online ahead of print.

ABSTRACT

PURPOSE: In vitro fertilization (IVF) is associated with abnormal trophoblast invasion and resultant decreased levels of circulating placental biomarkers such as placental growth factor (PlGF). Our objective was to evaluate maternal serum levels of second/third trimester PlGF, sonographic placental parameters, and clinical outcomes among IVF frozen embryo transfer (FET) pregnancies with and without embryo trophectoderm biopsy.

METHODS: This was a retrospective study of pregnant patients who conceived using a single frozen embryo transfer (FET) and gave birth between 30 January 2018 and 31 May 2021. We compared PlGF levels, sonographic placental parameters, and clinical outcomes between FET with biopsy and FET without biopsy groups.

RESULTS: The median PlGF level was 614.5 pg/mL (IQR 406-1020) for FET pregnancies with biopsy, and 717.0 pg/mL (IQR 552-1215) for FET pregnancies without biopsy. The adjusted mean difference was 190.9 pg/mL lower in the FET biopsy group (95% CI, -410.6, 28.8; p = 0.088). There were no statistically significant differences in placental parameters or clinical pregnancy outcomes.

CONCLUSION: This exploratory study demonstrated a possible trend toward lower maternal serum PlGF in the pregnancies conceived with FET using a biopsied embryo. Further investigation is warranted into the potential placental health effects of trophectoderm biopsy.

PMID:39042339 | DOI:10.1007/s10815-024-03193-8

Brain Topogr. 2024 Jul 23. doi: 10.1007/s10548-024-01068-w. Online ahead of print.

ABSTRACT

Most Event Related Potential studies investigating the time course of visual processing have focused mainly on the N170 component. Stimulus orientation affects the N170 amplitude for faces but not for objects, a finding interpreted as reflecting holistic/configural processing for faces and featural processing for objects. Furthermore, while recent studies suggest where on the face people fixate impacts the N170, fixation location effects have not been investigated in objects. A data-driven mass univariate analysis (all time points and electrodes) was used to investigate the time course of inversion and fixation location effects on the neural processing of faces and houses. Strong and widespread orientation effects were found for both faces and houses, from 100-350ms post-stimulus onset, including P1 and N170 components, and later, a finding arguing against a lack of holistic processing for houses. While no clear fixation effect was found for houses, fixation location strongly impacted face processing early, reflecting retinotopic mapping around the C2 and P1 components, and during the N170-P2 interval. Face inversion effects were also largest for nasion fixation around 120ms. The results support the view that facial feature integration (1) depends on which feature is being fixated and where the other features are situated in the visual field, (2) occurs maximally during the P1-N170 interval when fixation is on the nasion and (3) continues past 200ms, suggesting the N170 peak, where weak effects were found, might be an inflexion point between processes rather than the end of a feature integration into a whole process.

PMID:39042323 | DOI:10.1007/s10548-024-01068-w

Lasers Med Sci. 2024 Jul 23;39(1):190. doi: 10.1007/s10103-024-04143-7.

ABSTRACT

This meta-analysis evaluates the efficacy and safety of greenlight (PVP) and thulium laser vaporization (ThuVAP) in Benign Prostatic Hyperplasia (BPH) treatment. A systematic literature search was conducted in databases including PubMed, Cochrane Library, EMBASE, CNKI, Wangfang, and VIP in November 2023. Following the PRISMA guidelines, a systematic review and meta-analysis of the primary outcomes of interest were performed. The review was prospectively registered on PROSPERO under the registration number CRD42023491316. A total of 13 studies were included. The results of the meta-analysis showed that compared to PVP, ThuVAP had a shorter operation time (MD: 8.56, 95% CI: 4.10 ~ 13.03, p = 0.0002), and higher postoperative transfusion (OR:0.26, 95% CI: 0.10 ~ 0.64, p = 0.004). However, no significant differences were observed between the two groups in terms of length of stay (MD: -0.32, 95% CI: -0.78 ~ 0.14, p = 0.17), catherization time (MD: 0.03, 95% CI: -0.13 ~ 0.19, p = 0.73), international prostate symptom score improvement (MD: 0.23, 95% CI: -0.36 ~ 0.81, p = 0.45), quality of life improvement (MD: 0.04, 95% CI: -0.04 ~ 0.12, p = 0.29), maximum urinary flow rate improvement (MD: -0.59, 95% CI: -1.42 ~ 0.24, p = 0.16), postvoid residual urine volume improvement (MD: 1.04, 95% CI: -6.63 ~ 8.71, p = 0.79), overall postoperative complications (OR:1.15, 95% CI: 0.65 ~ 2.03, p = 0.63), postoperative bleeding (OR:1.18, 95% CI: 0.67 ~ 2.07, p = 0.56), re-peration (OR:0.55, 95% CI: 0.16 ~ 1.95, p = 0.35), urethral stricture (OR:0.90, 95% CI: 0.46 ~ 1.75, p = 0.75), and urinary incontinence (OR:1.07, 95% CI: 0.64 ~ 1.78, p = 0.80). The results of subgroup analysis showed that the results of comparing thulium vaporesection or vapoenucleation with PVP were consistent with the results of the pooled analysis. Both greenlight and thulium laser vaporization are effective and safe, with comparable surgical and functional outcomes. The choice between these methods should be based on patient-specific factors.

PMID:39042320 | DOI:10.1007/s10103-024-04143-7

Arch Dermatol Res. 2024 Jul 23;316(7):482. doi: 10.1007/s00403-024-03224-5.

ABSTRACT

BACKGROUND: In the absence of a gold-standard diagnostic modality for cellulitis, sterile inflammatory disorders may be misdiagnosed as cellulitis.

OBJECTIVE: To determine the utility of skin biopsy and tissue culture for the diagnosis and management of patients admitted with a diagnosis of presumed cellulitis.

DESIGN: Pilot single-blind parallel group randomized controlled clinical trial in 56 patients with a primary diagnosis of presumed cellulitis. In the intervention group only, skin biopsy and tissue culture results were made available to the primary care team to guide diagnosis and management. Length of hospital stay and antibiotic use were evaluated as outcome measures.

RESULTS: Length of stay showed the greatest opportunity for further study as a primary outcome (intervention: 4, IQR (2-6) vs. control: 5 IQR (3-8) days; p = 0.124).

LIMITATIONS: The COVID-19 pandemic placed limitations on participant enrollment and study duration; in addition, data was collected from a single medical center.

CONCLUSION: This study demonstrates that length of stay and anti-pseudomonal antibiotic de-escalation are endpoints that may be influenced by biopsy and tissue culture results in presumed cellulitis patients; these outcomes warrant further study.

PMID:39042316 | DOI:10.1007/s00403-024-03224-5

Biol Trace Elem Res. 2024 Jul 23. doi: 10.1007/s12011-024-04319-w. Online ahead of print.

ABSTRACT

Autism spectrum disorder (ASD) has become a global public health concern, impacting the quality of life. The question of gene-environment interaction in the emergence of ASD remains a subject of ongoing debate, and exploring its pathophysiology is thoroughly related to metals as a risk factor. Therefore, this study aims to assess the levels of toxic (Al, Cd, Hg, and Pb) and essential (Cr, Mn, Fe, Ni, Cu, Zn, and Se) elements in toenail samples collected in children with ASD and neurotypical children, by ICP-MS. Parallelly, we will discuss the use of toenails as an exposure indicator. The study involved 208 children aged 3 to 14 from Marrakech, Morocco. One hundred two were diagnosed with ASD and 106 were neurotypical children. Significant statistical differences in the concentration of Cr, Mn, and Fe were documented between the two groups. Higher levels of Pb in toenails compared to reference values have been reported. No association was established between concentrations of elements and age. Spearman correlation coefficients revealed a significantly different pattern of mutual dependence for toxic and essential elements between the two groups. The strongest positive correlations were found in the neurotypical group (Fe-Mn (ρ = 0.750), and Se-Zn (ρ = 0.800)). These results provide additional, although inconclusive, evidence on the probable role of element disturbance in the pathogenesis of ASD. Further studies should be performed to explore other nutritional, cultural, sociodemographic, environmental, and methodological factors that may impact the levels of these elements in the nails and their possible correlation with the incidence of ASD.

PMID:39042314 | DOI:10.1007/s12011-024-04319-w

J Oral Rehabil. 2024 Jul 23. doi: 10.1111/joor.13795. Online ahead of print.

ABSTRACT

BACKGROUND: Temporomandibular joint disorder (TMD), a prevalent orofacial disorder with complex aetiologies and considerable socioeconomic costs. This underscores the critical importance of developing a comprehensive understanding of the risk factors associated with TMD, as existing research is hindered by deficiencies in establishing causal relationships and the limitations of traditional research methodologies.

OBJECTIVES: This research explores the causal link between certain risk factors and temporomandibular joint disorder (TMD) through Mendelian randomization (MR), providing multidimensional perspectives in addressing this worldwide health issue.

METHODS: Utilizing instrumental variables, we applied advanced statistical methods, including the weighted median, inverse variance weighted (IVW) and MR-Egger, to evaluate the impact of twelve potential risk factors on TMD.

RESULTS: Our results identified a significant positive association of TMD with malocclusion (p < .001), sleeping disorders (p = .006), anxiety (p = .002), major depression (p = .0002), daily cigarettes consumption (p = .029) and autoimmune diseases (p = .039). Conversely, a negative association was observed with educational attainment (p = .003).

CONCLUSION: These findings suggest that malocclusion, sleeping disorders, anxiety, major depression, daily cigarettes consumption and autoimmune diseases, could potentially increase TMD risk while educational attainment might mitigate its increase. No direct causal relationships were established between serum 25-hydroxyvitamin D levels, menopause, frequent alcohol consumption, coffee intake and severely worn dentition and TMD.

PMID:39041331 | DOI:10.1111/joor.13795

Ophthalmic Physiol Opt. 2024 Jul 23. doi: 10.1111/opo.13369. Online ahead of print.

NO ABSTRACT

PMID:39041311 | DOI:10.1111/opo.13369

Alzheimers Dement. 2024 Jul 23. doi: 10.1002/alz.14077. Online ahead of print.

ABSTRACT

INTRODUCTION: Understanding attitudes toward participation among diverse preclinical Alzheimer’s disease (AD) trial participants could yield insights to instruct future recruitment.

METHODS: Using data from the Anti-Amyloid Treatment in Asymptomatic AD (A4) Study, we examined differences among mutually exclusive racial and ethnic groups in views and perceptions of amyloid imaging (VPAI), a measure of motivations to undergo amyloid biomarker testing in the setting of preclinical AD. We used linear regression to quantify differences at baseline.

RESULTS: Compared to non-Hispanic or Latino (NH) White participants, Hispanic or Latino (3.52 points, 95% confidence interval [CI]: [2.61, 4.42]); NH Asian (2.97 points, 95% CI: [1.71, 4.22]); and NH Black participants (2.79 points, 95% CI: [1.96, 3.63]) participants demonstrated higher levels of endorsement of the VPAI items at baseline.

DISCUSSION: Differences may exist among participants from differing ethnic and racial groups in motivations to undergo biomarker testing in the setting of a preclinical AD trial.

HIGHLIGHTS: Representative samples in AD clinical trials are vital to result in generalizability. We assessed motivations to undergo amyloid imaging in a preclinical AD trial. Racial and ethnic minority groups showed higher endorsement of VPAI items. Differences were driven by perceived risk, plan/prepare, and curiosity domains. Few observations among racial and ethnic groups changed after biomarker disclosure.

PMID:39041310 | DOI:10.1002/alz.14077