Category: Statistics

Avicenna J Med Biotechnol. 2024 Oct-Dec;16(4):260-267. doi: 10.18502/ajmb.v16i4.16742.

ABSTRACT

BACKGROUND: Simulated Physiological Oocyte Maturation (SPOM) mimics in vitro the physiological events of oocyte maturation in the presence of cAMP modulators. These modulators increase the intracellular concentrations of cAMP, which inhibits the immediate resumption of meiosis and gives the oocyte more time to gain optimal developmental competence. In addition, L-carnitine helps to increase the energy supply of cells through the β-oxidation of fatty acids. This study aimed to investigate the effect of SPOM and L-carnitine supplementation during In Vitro Maturation (IVM) and In Vitro Culture (IVC) on the developmental competence of bovine oocytes.

METHODS: Ovarian Cumulus Complexes (COCs) were cultured in the presence or absence of forskolin+IBMX during the first 2 hr of IVM (pre-IVM) with or without L-carnitine (LC) during IVM or IVC in six experimental groups as follows: I) pre-IVM (pre-IVM group), II) pre-IVM with L-carnitine supplementation during IVM (pre-IVM/LC group), III) L-carnitine supplementation during IVM (IVM/LC group), IV) L-carnitine supplementation during in vitro culture (IVC/LC group), V) pre-IVM+ IVC/LC group, and VI) no treatment during IVM and IVC (Control group). The cleavage and blastocyst rates, the blastocysts’ total cells number, and the expression of Nanog, Bax, Oct4, Cdx2, and Ifnt genes in resulting blastocysts were assessed. To assess differences among experimental groups, a one-way analysis of variance was initially employed, followed by post hoc Fisher LSD. The difference between groups was considered statistically significant when p<0.05.

RESULTS: The cleavage and blastocyst rates in the Pre-IVM and Pre-IVM/LC groups was higher than control group and other groups (p≤0.05) except for IVC/LC and IVM/LC groups, respectively. The number of blastocyst’s Inner Cell Mass (ICM) in pre-IVM and Pre-IVM/LC groups as well as the ratio of ICM/TE were higher than control group (p<0.05). The expression of OCT4, CDX2, and IFNT increased in both the pre-IVM and pre-IVM/LC groups compared to the control group (p<0.05).

CONCLUSION: In conclusion, the application of SPOM-adapted IVM and L-carnitine during IVM of bovine oocyte improves the quantity and quality of the resulting embryos.

PMID:39606683 | PMC:PMC11589426 | DOI:10.18502/ajmb.v16i4.16742

Front Med (Lausanne). 2024 Nov 13;11:1401685. doi: 10.3389/fmed.2024.1401685. eCollection 2024.

ABSTRACT

INTRODUCTION: Leprosy is a chronic infectious disease caused by the agent Mycobacterium leprae, characterized by its high disabling power. Data points to Brazil being the second country with the highest number of cases in the world, behind only India, representing a major challenge for public health. This work aims to determine the prevalence of paucibacillary (PB) cases in relation to leprosy cases in Brazil, using data published in the literature.

METHODS: This is a systematic review and meta-analysis carried out with studies from the last 20 years, being developed based on the Preferred Reporting Items for Systematic Review and Meta-analyzes (PRISMA).The search was carried out in the databases: PUBMED, SciELO, LILACS (via VHL)and Science Direct in October 2023, using the following descriptors (((“Brazil” [Mesh]) AND (“Leprosy, paucibacillary” [Mesh])) AND “Epidemiology” [Mesh]), in English, Portuguese and Spanish. Original studies of the analytical case-control, cohort, cross-sectional, epidemiological types were selected, as well as articles with satisfactory information for numerical extraction with separate data on the paucibacillary and multibacillary clinical forms. The methodological quality assessment followed the JBI critical appraisal checklist. Statistical analysis was performed using the Comprehensive Meta-Analyses-CMA software, version 3.0 (Biostat, Engewood, NJ, United States).

RESULTS: The meta-analysis of the 48 studies obtained a paucibacillary prevalence rate in Brazil of 50.5% or 0.505 (95% CI = 0.502-0.509).The differences in the analyzes were statistically significant (Q-value 4302.681;df 47; I 98.905), with a high heterogeneity value evidenced by I² (98.905). This analysis demonstrated that the frequency in the Midwest region was the highest and the South region was the lowest (21.4%). Begg’s (Kendall Tau p = 0.35) and Egger’s tests (p = 0.20) were performed, in which no high publication bias was noted. Subgroup analysis indicated that paucibacillary cases varied from region to region, with the Midwest region having the highest prevalence and the South region having the lowest.

CONCLUSION: The results stand out significantly for the research gaps that investigate PB cases, requiring more research aimed at investigating the paucibacillary clinical form that can contribute to the early diagnosis of leprosy.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO code: CRD42024514106.

PMID:39606626 | PMC:PMC11600445 | DOI:10.3389/fmed.2024.1401685

Wellcome Open Res. 2024 Sep 17;9:526. doi: 10.12688/wellcomeopenres.22699.1. eCollection 2024.

ABSTRACT

BACKGROUND: Hypertension affects over one billion people worldwide, posing a significant global health burden. Clinical practice guidelines could play a key role in guiding healthcare providers in improving hypertension management. However, how the quality of hypertension CPGs differs across country income settings is not well understood. This study aims to explore variation in the quality of hypertension CPGs, comparing low-, middle-, and high-income countries, using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool.

METHODS: A Medline and grey literature search was conducted to identify hypertension CPGs in English from every country from January 2012 to September 2022. Two reviewers independently assessed and scored each CPG against the AGREE II tool. Results were described and the Kruskal-Wallis test was used to test for statistically significant difference in the domain scores across country income groups.

RESULTS: Forty-three CPGs were included for analysis from across income settings. Guidelines from HICs scored higher in four out of the six domains. The highest scoring domain was 4: “clarity and presentation” (median score 83%), the lowest scoring was domain 6 “editorial independence” (median score 0%). Statistically significant differences between income settings were observed for domain 3 “rigour of development” (p <0.001), domain 4 “clarity and presentation” (p = 0.03) and domain 6 “editorial independence” (p = 0.04).

CONCLUSIONS: Whilst some variation exists in guideline quality across country income levels, the greatest degree of variation exists across the domains of the AGREE II tool. Global efforts to improve the quality of hypertension guidelines should focus on the transparent statement of editorial independence of guideline committees and apply rigorous replicable methods in the authoring of guidelines. Establishing national and international communities of practice to collaborate across income settings may reduce duplication of resource, allow for shared learning and promote the development of high-quality hypertension CPGs.

PMID:39606620 | PMC:PMC11599801 | DOI:10.12688/wellcomeopenres.22699.1

J Inherit Metab Dis. 2024 Nov 27. doi: 10.1002/jimd.12823. Online ahead of print.

ABSTRACT

Alterations in brain structure are frequently observed in adults with early-treated phenylketonuria (PKU) compared to healthy controls, with cerebral white matter (WM) being particularly affected. The extent to which temporary elevation of phenylalanine (Phe) levels impacts WM remains unclear. We conducted a double-blind, randomised, placebo-controlled crossover trial to investigate the effects of a 4-week high Phe exposure on cerebral WM and its relationship to cognitive performance and metabolic parameters in adults with PKU. In this study, 27 adults with early-treated classical PKU (aged 19-48 years) underwent diffusion tensor imaging (DTI) before and after the 4-week Phe and placebo interventions. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were analysed using tract-based spatial statistics. Neuropsychological examinations at each timepoint evaluated executive functions and attention. Additionally, brain Phe levels were measured using MR spectroscopy, and blood levels of Phe, tyrosine, and tryptophan were assessed after an overnight fast. Following the Phe period, significant decreases in AD, MD, and RD were observed compared to the placebo period, particularly in the posterior corona radiata and optic radiation. Notably, these WM changes were reversible in patients who first received Phe (n = 13). Cognitive performance and metabolic parameters were not significantly related to DTI scalars after the Phe period. In conlcusion, a 4-week Phe elevation induced reversible microstructural alterations in cerebral WM. Further investigation is necessary to determine the clinical implication of these changes.

PMID:39604093 | DOI:10.1002/jimd.12823

J Cachexia Sarcopenia Muscle. 2024 Nov 27. doi: 10.1002/jcsm.13615. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer cachexia can impact prognosis, cause resistance to anticancer treatments and affect the tolerability of treatments. This study aims to identify hepatocellular carcinoma (HCC) with cachexia by characterizing longitudinal body composition (BC) trajectories.

METHODS: This longitudinal, multicentre cohort study included unresectable HCC patients treated with first-line programmed death-(ligand)1 inhibitors plus anti-vascular endothelial growth factor antibody/tyrosine kinase inhibitors between 01/2018-12/2022. BC measurements including skeletal muscle mass (SMM) and total adipose tissue area (TATA) were evaluated by computed tomography at the third lumbar vertebra at baseline and follow-up imaging. Unsupervised latent class growth mixed models were applied to distinguish potential longitudinal SMM and TATA trajectories for identifying cachexia. The primary study endpoint was overall survival (OS), with secondary endpoints including progression-free survival (PFS), objective response rate (ORR) and safety. Multiple Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs) for survival.

RESULTS: A total of 411 patients with 2138 time-point measurements were included. The median age was 56 years, and 50 (12.2%) patients were female. Two distinct trajectories were identified for SMM and TATA: sharp-falling and stable. SMM sharply declined in 58 patients (14.1%) and TATA in 71 of 406 patients (17.5%) with significant worse OS (for SMM, 17.0 vs. 24.9 months; p < 0.001; HR = 0.59; for TATA, 15.3 vs. 25.1 months; p < 0.001; HR = 0.44). Patients were categorized into three phases based on trajectories: pre-cachexia (SMM and TATA stable, n = 299, 73.6%), cachexia (SMM or TATA sharp-falling, n = 86, 21.2%) and refractory cachexia (SMM and TATA sharp-falling, n = 21, 5.2%). Patients with refractory cachexia exhibited the worst OS, PFS and ORR, followed by those with cachexia. The median OS was 11.5 months for refractory cachexia, 17.7 for cachexia and 26.0 for pre-cachexia; median PFS was 6.0, 7.9 and 10.9 months, respectively, with ORR of 4.8%, 39.5% and 54.2%, respectively (all ps < 0.001). Multivariable Cox analysis identified refractory cachexia as an independent risk factor for both OS (HR = 3.31; p < 0.001) and PFS (HR = 2.94; p < 0.001), with cachexia also showing significant impacts. Grade 3-4 adverse events were higher in patients with refractory cachexia (23.8%) and cachexia (8.1%) compared with pre-cachexia (6.0%; p = 0.010).

CONCLUSIONS: HCC patients with cachexia and refractory cachexia were identified by longitudinal BC trajectories. Falling trajectories of BC identified refractory cachexia patients with worst response, survival and poor tolerability from systemic therapy combinations.

TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05278195.

PMID:39604073 | DOI:10.1002/jcsm.13615

Animal Model Exp Med. 2024 Nov 27. doi: 10.1002/ame2.12502. Online ahead of print.

ABSTRACT

The present study aims to establish a reproducible large animal experimental unit using a minipig model to monitor cardiac function changes. A 90-min closed-chest balloon occlusion of the left anterior descending branch of the coronary artery was used to induce myocardial infarction in Pannon minipigs. To monitor the cardiac function, measurements were made by cardiac magnetic resonance imaging (cMRI), invasive pressure monitoring, and a Pulse index Continuous Cardiac Output (PiCCO) hemodynamic system at 0, 72, and 720 h during the follow-up period. End-diastolic and end-systolic volumes (EDV, ESV), left ventricular ejection fraction (LVEF) obtained by cMRI evaluation, global ejection fraction and aortic dP/dt_max obtained by the invasive method, were recorded and compared. The 72- and 720-h EDV data showed a significant increase (p = 0.012, <0.001) compared to baseline, and the Day 30 data showed a significant increase compared to Day 3 (p = 0.022). The ESV 72 h after the infarction showed a significant increase (p = 0.001) compared to baseline, which did not change significantly by Day 30 (p = 0.781) compared to Day 3. EDV and ESV were significantly negatively correlated with aortic dp_max, and ESV was significantly correlated with LVEF. For LVEF and dP_max, a significant (p < 0.001 and p = 0.002) worsening was demonstrated at Day 3 compared to baseline, which was no longer statistically detectable for LVEF at Day 30 (p = 0.141), while the difference for dP_max was maintained (p = 0.002). The complementary use of PiCCO hemodynamic measurements in large animal models makes the previously used methodologies more robust and reliable.

PMID:39604064 | DOI:10.1002/ame2.12502

J Int AIDS Soc. 2024 Dec;27(12):e26371. doi: 10.1002/jia2.26371.

ABSTRACT

INTRODUCTION: Adverse metabolic effects related to dolutegravir (DTG) are increasingly reported as countries are adopting DTG-based regimens as first-line antiretroviral therapy (ART), but there is limited data from sub-Saharan Africa. We explored changes in body weight pre- and post-switch to a DTG-based regimen and assessed the association between DTG switch and significant weight gain (SWG) defined as a ≥10% increase over a 12-month period in people living with HIV (PLHIV) on ART in West Africa.

METHODS: We first included all PLHIV followed in the IeDEA West Africa cohorts between January 2017 and June 2021, with a documented switch to DTG during 2019-2021 and in care ≥36 months at the day of switch. Weight change was estimated using a two slope piecewise linear mixed model with change point at the switch date. Secondly, we emulated a sequence of target trials (ETT) based on the observational data, performing pooled logistic regression analysis to compare SWG occurrence between PLHIV who switched to DTG and those who did not.

RESULTS: We first included 6705 PLHIV from Burkina Faso, Côte d’Ivoire and Nigeria. Their median age at the time of switch was 48 years (IQR: 42-54) with a median follow-up of 9 years (IQR: 6-12), 63% were female. Most patients switched from efavirenz (EFV)-based ART (56.6%) and nevirapine (NVP)-based ART (30.9%). The overall post-switch annual average weight gain (AAWG) was significantly elevated at 3.07 kg/year [95% CI: 2.33-3.80] compared to the pre-switch AWG which stood at 0.62 kg/year [95% CI: 0.36-0.88]. The post-switch AWG was greater in patients previously on EFV and protease inhibitor (PI)-based ART compared to those on NVP-based ART. The pooled logistic regression analyses of a sequence of 24 ETT, including 9598 person-trials, switching to DTG was significantly associated with an SWG (aOR = 2.54; 95% CI = 2.18-2.97).

CONCLUSIONS: In West Africa, a 12-month DTG exposure was associated with substantial weight gain, especially in PLHIV previously on EFV and PI-based ARTs. Continuous weight monitoring and metabolic profiling is imperative in HIV cohorts to delineate the long-term cardiometabolic impact of DTG as patients with, or at elevated risk for cardiovascular diseases might benefit from alternative ART regimens.

PMID:39604062 | DOI:10.1002/jia2.26371

Ecology. 2024 Nov 27:e4490. doi: 10.1002/ecy.4490. Online ahead of print.

ABSTRACT

Although herbivory and allelopathy play important roles in plant invasions, their roles in mediating the effect of plant diversity on invasion resistance remain unknown. In a 2-year field experiment, we constructed native plant communities with four levels of species richness (one, two, four, and eight species) and used a factorial combination of insecticide and activated carbon applications to reduce herbivory and allelopathy, respectively. We then invaded the communities with the introduced plant Solidago canadensis L. One year after the start of the experiment, there was no statistically significant net effect of species richness on biomass of the invader. However, a structural equation model showed that species richness had a positive direct effect on invader biomass that was partially balanced out by a negative indirect effect of species richness via increased light interception. In the second year, the relationship between invader biomass and species richness was negative when we analyzed the treatment combination with herbivory and allelopathy separately. Therefore, we conclude that joint effects of herbivory and allelopathy may play major roles in driving the diversity-invasibility relationship and should be considered in future studies.

PMID:39604040 | DOI:10.1002/ecy.4490

Anaesthesia. 2024 Nov 27. doi: 10.1111/anae.16491. Online ahead of print.

ABSTRACT

INTRODUCTION: The number of tracheal intubation attempts required to reach proficiency in videolaryngoscopy with hyperangulated blades is unknown. Understanding this training requirement might guide training for clinicians who perform laryngoscopy. We therefore performed a planned sub-analysis of a randomised controlled trial comparing tracheal intubation success with videolaryngoscopy vs. direct laryngoscopy to determine the number of tracheal intubations with a hyperangulated videolaryngoscope blade needed to provide an acceptable first-attempt success rate.

METHODS: We included clinicians from a randomised controlled trial who were familiar with direct laryngoscopy and Macintosh-blade videolaryngoscopy but inexperienced with hyperangulated videolaryngoscopy. Cumulative sum statistics were used to generate learning curves with acceptable success rates of 85% and unacceptable success rates of 70% for the primary outcome of first-attempt tracheal intubation success.

RESULTS: We included 223 clinicians (25 consultants; 35 certified registered nurse anaesthetists; 36 student registered nurse anaesthetists; 46 fellows; and 81 residents) who attempted tracheal intubation in 4312 procedures. The median (IQR [range]) number of tracheal intubations per clinician was 15 (8-25 [1-77]). First-attempt failure was low, with only 72 failed first attempts overall, and was comparable across clinician groups. In total, 133 (60%) clinicians crossed the acceptable success rate boundary while the remaining 90 (40%) clinicians crossed neither the acceptable nor unacceptable success rate boundaries. Among clinicians who crossed the acceptance boundary, the median (IQR [range]) number of attempts for learning was 12 (12-12 [12-26]).

DISCUSSION: Clinicians experienced in tracheal intubation with direct laryngoscopy but unfamiliar with hyperangulated-blade videolaryngoscopy can achieve proficiency after approximately 12 attempts.

PMID:39604038 | DOI:10.1111/anae.16491

J Am Heart Assoc. 2024 Nov 27:e036046. doi: 10.1161/JAHA.124.036046. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension is a global health issue causing increased cardiovascular morbidity and mortality. Adherence to prescribed medication is a crucial factor in obtaining targeted outcomes, and fixed-dose combined antihypertensive pills (FCAPs) have been shown to help combat difficulties associated with polypharmacy management. This study investigated the influence of combination antihypertensives on blood pressure (BP) management.

METHODS AND RESULTS: Data from the 2013 to 2020 NHANES (National Health and Nutrition Examination Survey) were analyzed. Participants were included if between 18 and 79 years of age and were prescribed 2 antihypertensive classes. BP was deemed controlled if <140/<90 mm Hg. Examiner documentation and questionnaire data determined prescription antihypertensive medication usage and the presence of an FCAP. Descriptive statistics and multivariate regression analyses were used to compare the 2 groups. Subgroup analysis was performed for stricter BP goals of <130/<80 mm Hg. A total of 15 927 747 weighted participants met the inclusion criteria, 32.7% of whom were undergoing management with an FCAP. Participants with an FCAP were 1.78 (95% CI, 1.28-2.47, P=0.001) times more likely to have controlled BP (76.4% versus 67.3%) than those without an FCAP. Subgroup analysis revealed that FCAPs were associated with stricter BP goals (odds ratio [OR], 1.65, P=0.008; 87.6% versus 71.2%) compared with those without.

CONCLUSIONS: Participants with an FCAP were more likely to exhibit controlled BP, including participants with clinical atherosclerotic cardiovascular disease and those targeting stricter control. Clinicians can immediately and meaningfully affect their patient’s BP by opting for FCAPs.

PMID:39604035 | DOI:10.1161/JAHA.124.036046