Tag: pubmed

Eur Spine J. 2022 Jun 14. doi: 10.1007/s00586-022-07223-w. Online ahead of print.

ABSTRACT

PURPOSE: To determine whether the open or the minimally invasive transforaminal lumbar interbody fusion (O-TLIF, MI-TLIF) is the favored treatment, we provide first meta-analyses using prospective studies with at least two years follow-up only and present the clinical relevance of statistical results for the first time.

METHODS: After a systematic review of six databases, we conducted 10 meta-analyses of randomized controlled trials (RCTs) and 10 meta-analyses of eligible prospective studies (EPSs) to compare fusion rate, patient-reported outcome measures (back pain (B-VAS), leg pain, Oswestry Disability Index (ODI)), for the first time safety outcome measures as operative and postoperative complications per case, and the perioperative outcome measures estimated blood loss (EBL), operation time and length of hospital stay (LOS). The clinical relevance was assessed by overall effect sizes (OESs) of statistically significant meta-analytic results.

RESULTS: In our meta-analyses of RCTs, MI-TLIF is statistically significantly superior in ODI, EBL and LOS, with clinically meaningful OESs only in EBL and LOS. In meta-analyses of EPSs, MI-TLIF is statistically significantly superior in B-VAS, postoperative complications per case, EBL and LOS, all with clinically meaningful OESs except for B-VAS. The meta-analyses of remaining outcome measures present statistically nonsignificant results. In a descriptive analysis of complications, postoperative wound infections predominate in O-TLIF and hardware malposition in MI-TLIF.

CONCLUSION: After at least two years, O-TLIF and MI-TLIF can be considered equally efficacious, which simplifies surgeons’ decision between both treatments, however, with the safety outcome measure postoperative complications per case and the perioperative outcome measures EBL and LOS in favor of MI-TLIF. LEVEL OF EVIDENCE I: Well conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias.

PMID:35699832 | DOI:10.1007/s00586-022-07223-w

J Clin Immunol. 2022 Jun 14. doi: 10.1007/s10875-022-01301-w. Online ahead of print.

ABSTRACT

PURPOSE: A recent phase II open-label study of the interleukin 1 (IL-1) receptor antagonist (IL-1Ra) anakinra in treating IVIG-resistant Kawasaki disease (KD) patients reported promising results. Here, we aimed to characterize the immunological impact of IL-1 blockade in this unique study population.

METHODS: Patients’ and control sera and supernatants of cells (whole blood, neutrophils, coronary artery endothelial cells) stimulated with recombinant IL-1β were analyzed for single or multiple marker (n = 22) expression by ELISA or multiplexed bead array assay. Data were analyzed using unsupervised hierarchical clustering, multiple correlation, and multi-comparison statistics and were compared to retrospective analyses of KD transcriptomics.

RESULTS: Inflammation in IVIG-resistant KD (n = 16) is hallmarked by over-expression of innate immune mediators (particularly IL-6 > CXCL10 > S100A12 > IL-1Ra). Those as well as levels of immune or endothelial cell activation markers (sICAM-1, sVCAM-1) declined most significantly in course of anakinra treatment. Prior as well as following IL-1R blockade, over-expression of leucine-rich-α2-glycoprotein 1 (LRG1) associated best with remnant inflammatory activity and the necessity to escalate anakinra dosage and separated inflammatory KD patients from sJIA-MAS (n = 13) and MIS-C (n = 4). Protein as well as retrospective gene expression analyses indicated tight association of LRG1 with IL-1β signaling and neutrophilia, while particularly neutrophil stimulation with recombinant IL-1β resulted in concentration-dependent LRG1 release.

CONCLUSION: Our study identifies LRG1 as known trigger of endothelial activation and cardiac re-modeling to associate with IL-1β signaling in KD. Besides a potential patho-mechanistic implication of these findings, our data suggest blood leukocyte and neutrophil counts to best predict response to IL-1Ra treatment in IVIG-resistant KD.

PMID:35699824 | DOI:10.1007/s10875-022-01301-w

Lasers Med Sci. 2022 Jun 14. doi: 10.1007/s10103-022-03589-x. Online ahead of print.

ABSTRACT

This study aims to compare the results of both CO₂ laser and diode laser combined arytenoidectomy with posterior cordectomy in managing patients with bilateral vocal fold paralysis. A prospective study involved 80 bilateral vocal cord immobility patients in adduction. They are divided into two groups according to the laser used, whether CO₂ (with a wavelength of 10.6 µm) or diode (with a wavelength of 980 nm). We used mMRC (Modified Medical Research Council) dyspnea scale to assess dyspnea in our patients, while the voice was evaluated by both maximum phonation time and the voice handicap index. Quantitative variables were described using means and standard deviations, while categorical variables were described using frequencies and were compared using the chi-square test, Fisher exact test, and Monte Carlo test. There was a statistically non-significant difference between the studied groups regarding mMRC dyspnea scale and Voice Handicap Index preoperatively and postoperatively. There is a statistically significant difference between the two groups regarding maximum phonation time postoperatively (significantly higher in the CO₂ laser group) (p < 0.001). The CO₂ laser and diode laser could be used safely for the management of bilateral vocal cord paralysis. The CO₂ laser maintains better voice parameters and less postoperative pain, while the diode laser gives less operative time, lower cost, and simplicity of use.

PMID:35699806 | DOI:10.1007/s10103-022-03589-x

World J Microbiol Biotechnol. 2022 Jun 14;38(8):137. doi: 10.1007/s11274-022-03303-7.

ABSTRACT

The superior grade Daqu (S_Daqu) and normal grade Daqu (N_Daqu) have obvious differences in flavor, fracture surface, appearance, etc., which can be accurately grouped by well-trained panel based on their sensory properties. However, the differences in microbial community diversity and metabolites between the S_Daqu and N_Daqu were still unclear. The culture-dependent method, the third generation Pacific Biosciences (PacBio) single-molecule, real-time (SMRT) sequencing technology, and nuclear magnetic resonance (NMR) were combined to show the characteristics in microorganisms and metabolites. Results showed that the fungal counts were higher in N_Daqu while the richness of bacterial communities was higher in S_Daqu (P < 0.05). Lentibacillus, Burkholderia, Saccharopolyspora, Thermoascus, and Rasamsonia were the dominant genera of S_Daqu while Staphylococcus, Scopulibacillus, and Chromocleista were the dominant genera in N_Daqu. The content of differential acids, amino acids, and alcohols including fumarate, glucuronate, glycine, 4-carboxyglutamate, and myo-inositol in S_Daqu was higher than that in N_Daqu by ¹H NMR coupled with multivariate statistical analysis. The network analysis regarding microbes and metabolites suggested that Saccharopolyspora showed a strong positive correlation with 4-carboxyglutamate while Thermoascus and Chromocleista were highly negatively correlated with alanine and isobutyrate, respectively. Linear Discriminant Analysis (LDA) Effect Size (LEfSe) revealed that Macrococcus and Caulobacter were regarded as bacterial biomarkers in the S_Daqu while Chromocleista was the key fungal genera in N_Daqu. Functionality prediction indicated that the bacteria in S_Daqu were largely involved in more metabolic activities including biosynthesis, degradation, detoxification, and generation of precursor metabolite and energy.

PMID:35699790 | DOI:10.1007/s11274-022-03303-7

Int Urogynecol J. 2022 Jun 14. doi: 10.1007/s00192-022-05261-y. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: We aimed to determine whether the presence of metabolic syndrome (MS) affects the efficacy of mirabegron in treatment-naïve women with overactive bladder (OAB).

METHODS: Women being treated with mirabegron 50 mg were allocated to MS and non-MS groups, and the efficacy of treatment of OAB was compared using the OAB symptom score (OABSS) and a 3-day voiding diary before and 12 weeks after starting treatment. The Wilcoxon signed-rank and Mann-Whitney U tests and multivariate logistic regression were used for statistical analyses, and a p-value < 0.05 was considered to represent statistical significance.

RESULTS: Of the 197 patients who completed the trial, 43 (23.9%) had MS. After 12 weeks of mirabegron treatment, both the MS and non-MS groups showed significant improvements in OABSS score, the number of incontinence episodes/24 h, the number of micturition episodes/24 h, and the number of episodes of urgency/24 h. The factors associated with clinically important differences in OABSS were the presence of hyperglycemia (odds ratio 2.43, 95% confidence interval [CI] 1.05-5.60) and OABSS score at baseline (odds ratio 1.23, 95% CI 1.09-1.39).

CONCLUSIONS: Mirabegron is effective in patients with and without MS, and comorbid hyperglycemia and severe OAB symptoms before treatment are predictors of the efficacy of mirabegron treatment.

PMID:35699775 | DOI:10.1007/s00192-022-05261-y

Int Orthop. 2022 Jun 14. doi: 10.1007/s00264-022-05471-5. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to investigate the clinical and radiological progression of the patients who underwent proximal fibular partial excision (PFPE) for medial compartment knee osteoarthritis.

METHODS: Patients with medial compartment knee osteoarthritis who did not benefit from conservative treatment and accepted the PFPE surgery were involved in this study. Patients with traumatic arthritis, inflammatory arthritis, previous lower extremity fractures, valgus malalignment of the knee, and infection at the planned surgical site, however, were kept apart. Patients were assessed both clinically by Visual Analog Scale (VAS) and American Knee Society Score (AKSS), radiologically by Kellgren Lawrence classification, tibiofemoral angle, and joint-line convergence angle (JLCA). The patients were systematically assessed especially in the sixth month and first, second, and third years of the post-operative period.

RESULTS: A total of 35 patients (mean age: 56.5, min: 45, max: 79) were involved in this study. The mean follow-up period was 22.4 months (min: 6, max: 36). It has been observed that: Statistically significant decrease in VAS and increase in AKSS after PFPE (p < 0.001) No statistically significant improvement in preoperative and postoperative tibiofemoral angle and JLCA measurements CONCLUSIONS: The PFPE is a safe and effective surgical treatment for pain relief and functional improvement in medial compartment knee osteoarthritis. More studies are needed on its mechanism of action, long-term effects, and comparison with other treatment options.

PMID:35699745 | DOI:10.1007/s00264-022-05471-5

Anal Bioanal Chem. 2022 Jun 14. doi: 10.1007/s00216-022-04118-z. Online ahead of print.

ABSTRACT

Non-targeted analysis (NTA) methods are widely used for chemical discovery but seldom employed for quantitation due to a lack of robust methods to estimate chemical concentrations with confidence limits. Herein, we present and evaluate new statistical methods for quantitative NTA (qNTA) using high-resolution mass spectrometry (HRMS) data from EPA’s Non-Targeted Analysis Collaborative Trial (ENTACT). Experimental intensities of ENTACT analytes were observed at multiple concentrations using a semi-automated NTA workflow. Chemical concentrations and corresponding confidence limits were first estimated using traditional calibration curves. Two qNTA estimation methods were then implemented using experimental response factor (RF) data (where RF = intensity/concentration). The bounded response factor method used a non-parametric bootstrap procedure to estimate select quantiles of training set RF distributions. Quantile estimates then were applied to test set HRMS intensities to inversely estimate concentrations with confidence limits. The ionization efficiency estimation method restricted the distribution of likely RFs for each analyte using ionization efficiency predictions. Given the intended future use for chemical risk characterization, predicted upper confidence limits (protective values) were compared to known chemical concentrations. Using traditional calibration curves, 95% of upper confidence limits were within ~tenfold of the true concentrations. The error increased to ~60-fold (ESI+) and ~120-fold (ESI-) for the ionization efficiency estimation method and to ~150-fold (ESI+) and ~130-fold (ESI-) for the bounded response factor method. This work demonstrates successful implementation of confidence limit estimation strategies to support qNTA studies and marks a crucial step towards translating NTA data in a risk-based context.

PMID:35699740 | DOI:10.1007/s00216-022-04118-z

JAMA. 2022 Jun 14;327(22):2201-2209. doi: 10.1001/jama.2022.8274.

ABSTRACT

IMPORTANCE: African American smokers have among the highest rates of tobacco-attributable morbidity and mortality in the US, and effective treatment is needed for all smoking levels.

OBJECTIVES: To evaluate the efficacy of varenicline vs placebo among African American adults who are light, moderate, and heavy daily smokers.

DESIGN, SETTING, AND PARTICIPANTS: The Kick It at Swope IV (KIS-IV) trial was a randomized, double-blind, placebo-controlled clinical trial conducted at a federally qualified health center in Kansas City. A total of 500 African American adults who were daily smokers of all smoking levels were enrolled from June 2015 to December 2017; final follow-up was completed in June 2018.

INTERVENTIONS: Participants were provided 6 sessions of culturally relevant individualized counseling and were randomized (in a 3:2 ratio) to receive varenicline (1 mg twice daily; n = 300) or placebo (n = 200) for 12 weeks. Randomization was stratified by sex and smoking level (1-10 cigarettes/d [light smokers] or >10 cigarettes/d [moderate to heavy smokers]).

MAIN OUTCOMES AND MEASURES: The primary outcome was salivary cotinine-verified 7-day point prevalence smoking abstinence at week 26. The secondary outcome was 7-day point prevalence smoking abstinence at week 12, with subgroup analyses for light smokers (1-10 cigarettes/d) and moderate to heavy smokers (>10 cigarettes/d).

RESULTS: Among 500 participants who were randomized and completed the baseline visit (mean age, 52 years; 262 [52%] women; 260 [52%] light smokers; 429 [86%] menthol users), 441 (88%) completed the trial. Treating those lost to follow-up as smokers, participants receiving varenicline were significantly more likely than those receiving placebo to be abstinent at week 26 (15.7% vs 6.5%; difference, 9.2% [95% CI, 3.8%-14.5%]; odds ratio [OR], 2.7 [95% CI, 1.4-5.1]; P = .002). The varenicline group also demonstrated greater abstinence than the placebo group at the end of treatment week 12 (18.7% vs 7.0%; difference, 11.7% [95% CI, 6.0%-17.7%]; OR, 3.0 [95% CI, 1.7-5.6]; P < .001). Smoking abstinence at week 12 was significantly greater for individuals receiving varenicline compared with placebo among light smokers (22.1% vs 8.5%; difference, 13.6% [95% CI, 5.2%-22.0%]; OR, 3.0 [95% CI, 1.4-6.7]; P = .004) and among moderate to heavy smokers (15.1% vs 5.3%; difference, 9.8% [95% CI, 2.4%-17.2%]; OR, 3.1 [95% CI, 1.1-8.6]; P = .02), with no significant smoking level × treatment interaction (P = .96). Medication adverse events were generally comparable between treatment groups, with nausea reported more frequently in the varenicline group (163 of 293 [55.6%]) than the placebo group (90 of 196 [45.9%]).

CONCLUSIONS AND RELEVANCE: Among African American adults who are daily smokers, varenicline added to counseling resulted in a statistically significant improvement in the rates of 7-day point prevalence smoking abstinence at week 26 compared with counseling and placebo. The findings support the use of varenicline in addition to counseling for tobacco use treatment among African American adults who are daily smokers.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02360631.

PMID:35699705 | DOI:10.1001/jama.2022.8274

Stat Med. 2022 Mar 14. doi: 10.1002/sim.9373. Online ahead of print.

ABSTRACT

The mixture cure model for analyzing survival data is characterized by the assumption that the population under study is divided into a group of subjects who will experience the event of interest over some finite time horizon and another group of cured subjects who will never experience the event irrespective of the duration of follow-up. When using the Bayesian paradigm for inference in survival models with a cure fraction, it is common practice to rely on Markov chain Monte Carlo (MCMC) methods to sample from posterior distributions. Although computationally feasible, the iterative nature of MCMC often implies long sampling times to explore the target space with chains that may suffer from slow convergence and poor mixing. Furthermore, extra efforts have to be invested in diagnostic checks to monitor the reliability of the generated posterior samples. A sampling-free strategy for fast and flexible Bayesian inference in the mixture cure model is suggested in this article by combining Laplace approximations and penalized B-splines. A logistic regression model is assumed for the cure proportion and a Cox proportional hazards model with a P-spline approximated baseline hazard is used to specify the conditional survival function of susceptible subjects. Laplace approximations to the posterior conditional latent vector are based on analytical formulas for the gradient and Hessian of the log-likelihood, resulting in a substantial speed-up in approximating posterior distributions. The spline specification yields smooth estimates of survival curves and functions of latent variables together with their associated credible interval are estimated in seconds. A fully stochastic algorithm based on a Metropolis-Langevin-within-Gibbs sampler is also suggested as an alternative to the proposed Laplacian-P-splines mixture cure (LPSMC) methodology. The statistical performance and computational efficiency of LPSMC is assessed in a simulation study. Results show that LPSMC is an appealing alternative to MCMC for approximate Bayesian inference in standard mixture cure models. Finally, the novel LPSMC approach is illustrated on three applications involving real survival data.

PMID:35699121 | DOI:10.1002/sim.9373

Stat Med. 2022 Mar 17. doi: 10.1002/sim.9376. Online ahead of print.

ABSTRACT

The article develops marginal models for multivariate longitudinal responses. Overall, the model consists of five regression submodels, one for the mean and four for the covariance matrix, with the latter resulting by considering various matrix decompositions. The decompositions that we employ are intuitive, easy to understand, and they do not rely on any assumptions such as the presence of an ordering among the multivariate responses. The regression submodels are semi-parametric, with unknown functions represented by basis function expansions. We use spike-slap priors for the regression coefficients to achieve variable selection and function regularization, and to obtain parameter estimates that account for model uncertainty. An efficient Markov chain Monte Carlo algorithm for posterior sampling is developed. The simulation study presented investigates the gains that one may have when considering multivariate longitudinal analyses instead of univariate ones, and whether these gains can counteract the negative effects of missing data. We apply the methods on a highly unbalanced longitudinal dataset with four responses observed over a period of 20 years.

PMID:35699116 | DOI:10.1002/sim.9376