Tag: statistics

RMD Open. 2023 Aug;9(3):e003220. doi: 10.1136/rmdopen-2023-003220.

ABSTRACT

OBJECTIVES: To evaluate mediating factors for the effect of therapeutic exercise on pain and physical function in people with knee/hip osteoarthritis (OA).

METHODS: For Subgrouping and TargetEd Exercise pRogrammes for knee and hip OsteoArthritis (STEER OA), individual participant data (IPD) were sought from all published randomised controlled trials (RCTs) comparing therapeutic exercise to non-exercise controls in people with knee/hip OA. Using the Counterfactual framework, the effect of the exercise intervention and the percentage mediated through each potential mediator (muscle strength, proprioception and range of motion (ROM)) for knee OA and muscle strength for hip OA were determined.

RESULTS: Data from 12 of 31 RCTs of STEER OA (1407 participants) were available. Within the IPD data sets, there were generally statistically significant effects from therapeutic exercise for pain and physical function in comparison to non-exercise controls. Of all potential mediators, only the change in knee extension strength was statistically and significantly associated with the change in pain in knee OA (β -0.03 (95% CI -0.05 to -0.01), 2.3% mediated) and with physical function in knee OA (β -0.02 (95% CI -0.04 to -0.00), 2.0% mediated) and hip OA (β -0.03 (95% CI -0.07 to -0.00), no mediation).

CONCLUSIONS: This first IPD mediation analysis of this scale revealed that in people with knee OA, knee extension strength only mediated ±2% of the effect of therapeutic exercise on pain and physical function. ROM and proprioception did not mediate changes in outcomes, nor did knee extension strength in people with hip OA. As 98% of the effectiveness of therapeutic exercise compared with non-exercise controls remains unexplained, more needs to be done to understand the underlying mechanisms of actions.

PMID:37640513 | DOI:10.1136/rmdopen-2023-003220

J Gene Med. 2023 Aug 28:e3583. doi: 10.1002/jgm.3583. Online ahead of print.

ABSTRACT

BACKGROUND: Although defects in sperm morphology and physiology lead to male infertility, in many instances, the exact disruption of molecular pathways in a given patient is often unknown. The glycolytic pathway is an essential process to supply energy in sperm cell motility. Enolase 4 (ENO4) is crucial for the glycolytic process, which provides the energy for sperm cells in motility. ENO4 is located in the sperm principal piece and is essential for the motility and organization of the sperm flagellum. In the present study, we characterized a family with asthenozoospermia and abnormal sperm morphology as a result of a variant in the enolase 4 (ENO4) gene.

METHODS: Computer-assisted semen analysis, papanicolaou smear staining and scanning electron microscopy were used to examine sperm motility and morphology for semen analysis in patients. For genetic analysis, whole-exome sequencing followed by Sanger sequencing was performed.

RESULTS: Two brothers in a consanguineous family were being clinically investigated for sperm motility and morphology issues. Genetic analysis by whole-exome sequencing revealed a homozygous variant [c.293A>G, p.(Lys98Arg)] in the ENO4 gene that segregated with infertility in the family, shared by affected but not controls.

CONCLUSIONS: In view of the association of asthenozoospermia and abnormal sperm morphology in Eno4 knockout mice, we consider this to be the first report describing the involvement of ENO4 gene in human male infertility. We also explore the possible involvement of another variant in explaining other phenotypic features in this family.

PMID:37640479 | DOI:10.1002/jgm.3583

BMJ Open. 2023 Aug 28;13(8):e068445. doi: 10.1136/bmjopen-2022-068445.

ABSTRACT

OBJECTIVE: The purpose of this research was to determine the prevalence of diabetes and pre-diabetes in Sri Lanka.

DESIGN: Systematic review and meta-analysis.

DATA SOURCES: MEDLINE (via PubMed), Web of Science, Sri Lankan Journals online and Google Scholar were searched for relevant articles published between January 1990 and June 2022 investigating the prevalence of pre-diabetes and diabetes in Sri Lanka.

METHODS: Random effect meta-analyses were conducted to derive the pooled prevalence of pre-diabetes and diabetes and their 95% CIs. Heterogeneity was explored by subgroup and meta-regression analyses. Sensitivity analyses were used to evaluate the impact of any single study on the pooled estimates. Two authors screened articles, extracted data and evaluated the quality of selected studies.

RESULTS: A total of 479 articles were reviewed, and 15 studies (n=30 137 participants) were selected in the final analysis. The overall pooled prevalence of diabetes was 12.07% (95% CI, 8.71% to 15.89%; prediction interval: 1.28-31.35). The pooled pre-diabetes prevalence was 15.57% (95% CI, 9.45% to 22.88%; prediction interval: 0.02-49.87). The pooled type 2 diabetes prevalence was the highest in the latest period of 2011-2021 (17.25%) than in the period of 2000s (11.84%) and 1990s (5.62%).

CONCLUSIONS: The growing trend of diabetes and pre-diabetes over the last 30 years is alarming in Sri Lanka. The government of Sri Lanka needs to take steps to improve diabetes education, screening, diagnosis and treatment.

PROSPERO REGISTRATION NUMBER: CRD42021288591.

PMID:37640460 | DOI:10.1136/bmjopen-2022-068445

Intest Res. 2023 Aug 29. doi: 10.5217/ir.2023.00004. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: The impact of coronavirus disease 2019 (COVID-19) on the management of colorectal cancer (CRC) may worse in elderly population, as almost all COVID-19 deaths occurred in the elderly patients. This study aimed to evaluate the impact of COVID-19 on CRC management in the elderly population.

METHODS: The numbers of patients who underwent colonoscopy, who visited hospitals or operated for CRC in 2020 and 2021 (COVID-19 era) were compared with those in 2019, according to 3 age groups (≥70 years, 50-69 years, and ≤49 years), based on the nationwide, population-based database (2019-2021) in South Korea.

RESULTS: The annual volumes of colonoscopy and hospital visits for CRC in 2020 were more significantly declined in the old age group than in the young age group (both P<0.001). In addition, the annual volume of patients operated for CRC numerically more declined in old age group than in young age group. During the first surge of COVID-19 (March and April 2020), old age patients showed statistically significant declines for the monthly number of colonoscopies (-46.5% vs. -39.3%, P<0.001), hospital visits (-15.4% vs. -7.9%, P<0.001), CRC operations (-33.8% vs. -0.7%, P<0.05), and colonoscopic polypectomies (-41.8% vs. -38.0%, P<0.001) than young age patients, compared with those of same months in 2019.

CONCLUSIONS: Elderly population are more vulnerable for the management of CRC during the COVID-19 pandemic. Therefore, the elderly population are more carefully cared for in the management of CRC during the next pandemic.

PMID:37640379 | DOI:10.5217/ir.2023.00004

Respir Med. 2023 Aug 26:107393. doi: 10.1016/j.rmed.2023.107393. Online ahead of print.

ABSTRACT

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 μg/12 μg combination vs monotherapies and placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease (COPD). Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV₁) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124; p < 0.001), and in trough FEV₁ vs formoterol (LS mean 85 mL; 95% CI 53, 117; p < 0.001). Furthermore, aclidinium monotherapy provided improvements in trough FEV₁ vs placebo (LS mean 134 mL; 95% CI 103, 166; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not aclidinium vs placebo (LS mean 0.4; 95% CI -0.1, 1.0; p = 0.132). Improvements in St George’s Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean -4.0; 95% CI -6.7, -1.4; p = 0.003) and aclidinium vs placebo (LS mean -2.9; 95% CI -5.5, -0.3; p = 0.031). Aclidinium/formoterol and aclidinium monotherapy were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent (TE) adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively) and AEs leading to discontinuation of study medication (2.3,1.5, and 2.2%, respectively) were similar between groups.

PMID:37640273 | DOI:10.1016/j.rmed.2023.107393

Am J Med Sci. 2023 Aug 26:S0002-9629(23)01317-4. doi: 10.1016/j.amjms.2023.08.008. Online ahead of print.

ABSTRACT

BACKGROUND: Congestion is the main cause of morbidity and a prime determinant of survival in patients with heart failure (HF). However, the assessment of congestion is subjective and estimation of plasma volume (ePV) has been suggested as a more objective measure of congestion. This study aimed to explore the relationships and interactions between ePV, the severity of congestion and survival using a nationwide registry.

METHODS: Of the 1054 patients with HF enrolled in the registry, 769 had sufficient data to calculate ePV (using the Duarte, Kaplan, and Hakim equations) and relative plasma volume status (rPVS), and these patients were subsequently included in the present analysis. The severity of congestion was assessed using a 6-point congestion score (CS). Patients were divided into three groups according to the degree of congestion.

RESULTS: Out of four equations tested, only ePV_Duarte and rPVS were statistically higher in patients with severe congestion as compared to patients with no congestion (p<0.001 for both). Both ePV_Duarte (r=0.197, p<0.001) and rPVS (r=0.153, p<0.001) showed statistically significant correlations with CS and both had a modest accuracy (70.4% for ePV_Duarte and 69.4% for rPVS) to predict a CS ≥3. After a median follow up of 496 days, both ePV_Duarte (OR:1.14,95%CI:1.03-1.26, p=0.01) and rPVS (OR:1.02, 95%CI:1.00-1.03, p=0.03) were associated with all-cause mortality after adjusting for demographic and clinical variables. However, none of the indices were associated with mortality following the introduction of CS to the models (p>0.05 for both).

CONCLUSIONS: Elevated ePV_Duarte and rPVS were indicators of congestion but with a limited robustness, and either parameter could be clinically useful when a comprehensive clinical evaluation of congestion is not feasible.

PMID:37640264 | DOI:10.1016/j.amjms.2023.08.008

J Ethnopharmacol. 2023 Aug 26:117090. doi: 10.1016/j.jep.2023.117090. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Anxiety disorders leads to a decline in quality of life and increased risk of morbidity and mortality. The Baihe Dihuang decoction (BDD) is a classic Chinese medical formula that has been widely used to treat anxiety disorders for thousands of years in China. However, the pharmacodynamic material that is responsible for the antianxiety of BDD remains unclear.

AIM OF THE STUDY: To screen the main ingredients of anti-anxiety in BDD based on the establishment of spectrum-effect relationship and verified experiment.

METHODS: The UPLC-Q-TOF/MS technique was utilized to establish fingerprints of various fractions of BDD and identify the main compounds. The anti-anxiety effects of BDD were comprehensively evaluated through multiple assessments, including the open field test, elevated plus maze test, and neurotransmitters tests. Then, the spectrum-effect relationship was established through Pearson correlation analysis, gray correlation analysis, orthogonal partial least squares regression analysis. The spectrum-effect relationship results were confirmed through various measures on an anxiety condition cell model, induced by a corticosterone and lipopolysaccharide intervention. These measures included assessing neuronal cell viability, morphology, apoptosis, synaptic damage, and the expression of neurotransmitters and inflammatory factors.

RESULTS: In the UPLC-Q-TOF-MS fingerprint, 46 common peaks were identified. The pharmacological results indicated that different fractions of BDD have strong effects on improving anxiety-like behavior and regulating neurotransmitters. Among them, butanol fraction has the highest comprehensive evaluation score of anti-anxiety efficacy, which is main active fraction of BDD for anti-anxiety. The analysis of the spectrum-effect relationship revealed that the 46 peaks exhibited varying degrees of correlation with the anti-anxiety efficacy indicators of BDD. Among them, 14 components have a high correlation with the anti-anxiety efficacy indicators, which may be the potential anti-anxiety efficacy components of BDD. The in vitro activity verification of active components verified our prediction, regaloside A, B, C, D, H, acteoside, and isoacteoside improved neuronal cell viability, cell morphology, apoptosis, and synaptic damage. Additionally, regaloside A, B, C, D, H and acteoside regulated the neurotransmitter levels, while regaloside A, B, C, D, acteoside and isoacteoside inhibited the levels of inflammatory cytokines.

CONCLUSION: The butanol fraction was found to be the main active fraction of BDD, and 14 compounds were the major anxiolytic active components. The results of verifying the major active components were consistent with the predicted results of the spectrum-effect analysis. The developed spectrum-effect analysis in this study demonstrates high accuracy and reliability for screening active components in TCMs.

PMID:37640258 | DOI:10.1016/j.jep.2023.117090

J Oral Maxillofac Surg. 2023 Aug 13:S0278-2391(23)00800-5. doi: 10.1016/j.joms.2023.08.004. Online ahead of print.

ABSTRACT

BACKGROUND: Condylar adaptations following orthognathic surgery remain an area of interest. Prior studies do not use 3-dimensional imaging modalities and lack standardization in the choice of osteotomy and movement when assessing condylar changes.

PURPOSE: The purpose of this study was to use 3-dimensional cephalometry to measure the association between osteotomy type (sagittal split osteotomy [SSO] vs vertical ramus osteotomy [VRO]) and changes in condylar volume and position.

STUDY DESIGN, SETTING, AND SAMPLE: This is a retrospective cohort study from January 2021 through December 2022 of patients at Bellevue Hospital in New York City, New York who were treated with either SSO or VRO for the correction of Class III skeletal malocclusion.

PREDICTOR/EXPOSURE/INDEPENDENT VARIABLE: The primary predictor was the type of mandibular osteotomy, sagittal split osteotomy, and vertical ramus osteotomy.

MAIN OUTCOME VARIABLES: The primary outcomes were changes in condylar volume (change measured in mm³) and relative position (anterior-posterior change utilizing the Pullinger and Hollinder method).

COVARIATES: Covariates included patient age, sex, setback magnitude, temporomandibular joint symptoms, and fixation method for SSO patients.

ANALYSES: Univariate comparisons were performed between independent variables and study outcomes. Volume changes were compared within each predictor using paired t-tests. Position changes were compared within each predictor using χ² tests. If there were multiple significant univariate predictors, multiple regression models were created to predict volume and position changes. A P < .05 value was considered statistically significant.

RESULTS: The final sample comprised 30 condyles derived from 30 subjects. Mean age was 22.7 years (SD = 5.7) and mean setback was 3.9 mm (SD = 0.9). Twenty two condyles (73.3%) were subject to SSO with fixation, while the remaining 8 (26.7%) condyles were subject to intraoral VRO without fixation. When compared to VRO, condyles manipulated with SSO had greater volume loss (-177.2 vs -60.9 mm³; P = .03) and positional change (68.2 vs 12.5%; P < .01). Self-reported measures of postoperative pain, internal derangement, and myofascial symptoms were not significantly associated with either volume or positional changes.

CONCLUSIONS AND RELEVANCE: The SSO resulted in greater postoperative condylar volume loss and positional changes. These volume and positional changes were not correlated with self-reported temporomandibular disorder symptoms.

PMID:37640238 | DOI:10.1016/j.joms.2023.08.004

J Pediatr. 2023 Aug 26:113700. doi: 10.1016/j.jpeds.2023.113700. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the ability of the Bayley-III cognitive and language composite scores at 18-22 months corrected age to predict WISC-IV Full Scale IQ (FSIQ) at 6-7 years in infants born extremely preterm.

STUDY DESIGN: Children in this study were part of the Neuroimaging and Neurodevelopmental Outcome (NEURO) cohort, a secondary study to the SUPPORT trial and born 24 to 27.6 weeks gestational age. Bayley-III cognitive and language scores and WISC-IV FSIQ were compared with pairwise Pearson correlation coefficients and adjusted for medical and socio-economic variables using linear mixed effect regression models.

RESULTS: Bayley-III cognitive (r=0.33) and language scores (r=0.44) were mildly correlated with WISC-IV FSIQ score. Of the children with Bayley-III cognitive scores less than 70, 67% also had FSIQ <70. There was less consistency for children with Bayley-III scores in the 85-100 range as 43% had FSIQ <85 and 10% FSIQ <70. Among those with Bayley-III language scores >100, about 1 in 5 had FSIQ <85. A cut point of 92 for the cognitive composite score resulted in sensitivity (0.60), specificity (0.64). A cut point of 88 for the language composite score produced sensitivity (0.61), specificity (0.70).

CONCLUSION: Findings indicate the Bayley-III cognitive and language scores correlate with later IQ but may fail to predict delay or misclassify children who are not delayed at school age. The Bayley-III can be a useful tool to help identify children born extremely preterm who have below average cognitive scores and may be at the greatest risk for ongoing cognitive difficulties.

PMID:37640232 | DOI:10.1016/j.jpeds.2023.113700

Environ Pollut. 2023 Aug 26:122465. doi: 10.1016/j.envpol.2023.122465. Online ahead of print.

ABSTRACT

The estimated health effects of air pollution vary between studies, and this variation is caused by factors associated with the study location, hereafter termed regional heterogeneity. This heterogeneity raises a methodological question as to which studies should be used to estimate risks in a specific region in a health impact assessment. Should one use all studies across the world, or only those in the region of interest? The current study provides novel insight into this question in two ways. Firstly, it presents an up-to-date analysis examining the magnitude of continent-level regional heterogeneity in the short-term health effects of air pollution, using a database of studies collected by Orellano et al. (2020). Secondly, it provides in-depth simulation analyses examining whether existing meta-analyses are likely to be underpowered to identify statistically significant regional heterogeneity, as well as evaluating which meta-analytic technique is best for estimating region-specific estimates. The techniques considered include global and continent-specific (sub-group) random effects meta-analysis and meta-regression, with omnibus statistical tests used to quantify regional heterogeneity. We find statistically significant regional heterogeneity for 4 of the 8 pollutant-outcome pairs considered, comprising NO₂, O₃ and PM_2.5 with all-cause mortality, and PM_2.5 with cardiovascular mortality. From the simulation analysis statistically significant regional heterogeneity is more likely to be identified as the number of studies increases (between 3 and 30 in each region were considered), between region heterogeneity increases and within region heterogeneity decreases. Finally, while a sub-group analysis using Cochran’s Q test has a higher median power (0.71) than a test based on the moderators’ coefficients from meta-regression (0.59) to identify regional heterogeneity, it also has an inflated type-1 error leading to more false positives (median errors of 0.15 compared to 0.09).

PMID:37640226 | DOI:10.1016/j.envpol.2023.122465