Tag: nevin manimala

Ther Innov Regul Sci. 2022 Jun 14. doi: 10.1007/s43441-022-00420-1. Online ahead of print.

ABSTRACT

BACKGROUND/AIM: DARE-19 (NCT04350593) was a randomized trial studying the effects of dapagliflozin, an SGLT2 inhibitor, in hospitalized patients with COVID-19 pneumonia and cardiometabolic risk factors. The conduct of DARE-19 offered the opportunity to define an innovative and clinically meaningful endpoint in a new disease that would best reflect the known profile of dapagliflozin, accompanied by the statistical challenges of analysis and interpretation of such a novel endpoint.

METHODS: Hierarchical composite endpoints (HCEs) are based on clinical outcomes which, unlike traditional composite endpoints incorporate ranking of components according to clinical importance. Design of an HCE requires the clinical considerations specific to the therapeutic area under study and the mechanism of action of the investigational treatment. Statistical aspects for the clinical endpoints include the proper definition of the estimand as suggested by ICH E9(R1) for the precise specification of the treatment effect measured by an HCE.

RESULTS: We describe the estimand of the DARE-19 trial, where an HCE was constructed to capture the treatment effect of dapagliflozin in hospitalized patients with COVID-19, and was analyzed using a win odds. Practical aspects of designing new studies based on an HCE are described. These include sample size, power, and minimal detectable effect calculations for an HCE based on the win odds analysis, as well as handling of missing data and the clinical interpretability of the win odds in relation to the estimand.

CONCLUSIONS: HCEs are flexible endpoints that can be adapted for use in different therapeutic areas, with win odds as the analysis method. DARE-19 is an example of a COVID-19 trial with an HCE as one of the primary endpoints for estimating a clinically interpretable treatment effect in the COVID-19 setting.

PMID:35699910 | DOI:10.1007/s43441-022-00420-1

Hepatol Int. 2022 Jun 14. doi: 10.1007/s12072-022-10357-0. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Whether the efficacies of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) in treating liver-related outcomes of decompensated chronic hepatitis B (CHB) patients are comparable remained inconclusive.

METHODS: An 8-year cohort study of 736 decompensated CHB patients was conducted, and 65 TDF-treated patients were sex, age and model for end-stage liver disease (MELD) scores-1:4 matched with 260 ETV-treated patients through propensity score-matching method.

RESULTS: Of 736 patients, 574 (78%) were male, with a mean age of 54.3 years, 438 (59.5%) had cirrhosis, 147 (20%) were positive for HBeAg, and 84 (11.6%) and 652 (88.4%) were treated with TDF and ETV, respectively. The 652 ETV-treated patients were older, had higher baseline MELD score and rates of encephalopathy, but lower ALT levels than the 84 TDF-treated patients. No significant differences were observed in the cumulative incidences of liver-related mortality or liver transplantation (1-month, 18.45 vs. 14.01%, p = 0.368; 8-year, 39.74 vs. 34.24%, p = 0.298), and hepatocellular carcinoma development (5-year, 7.21 vs.13.17%, p = 0.994; 8-year, 11.60 vs.13.17%, p = 0.857) between the matched 260 ETV- and 65 TDF-treated patients, regardless of time points. Baseline MELD score (subdistribution hazard ratio (sHR): 1.063; 95% confidence interval (CI) of sHR: 1.016-1.112) and hepatic encephalopathy (sHR: 5.127; 95% CI sHR: 3.032-8.669) were independently associated with liver-related mortality or liver transplantation in the matched patients.

CONCLUSIONS: ETV and TDF had comparable efficacy in the short- and long-term liver-related outcomes of decompensated CHB patients, and baseline liver reserve was associated with the outcomes.

PMID:35699864 | DOI:10.1007/s12072-022-10357-0

Adv Exp Med Biol. 2022 Jun 15. doi: 10.1007/5584_2022_722. Online ahead of print.

ABSTRACT

The availability of virucidal compounds to reduce the impact of respiratory viruses is a relevant topic for public health, especially during the recent coronavirus disease (COVID-19) pandemic. Antimicrobial properties of Xibornol are known since the 1970s, but its activity on viruses is currently little explored. In this study, Xibornol activity at a fixed concentration of 0.03 mg/100 ml has been evaluated on five respiratory viruses (Human Adenovirus 5, Human Rhinovirus type 13, Human Coronavirus 229E, Human Parainfluenza Virus type 1, and Human Respiratory Syncytial Virus) through in vitro experiments based on adapted European standard UNI EN 14476-20019. The experiments were carried out under two different environmental conditions, one with the addition of fetal bovine serum to simulate an in vivo condition (dirty condition) and the other without the addition of any organic substances (clean condition). The viral abatement of Xibornol (expressed as Log₁₀ reduction – LR) was statistically significant under both clean and dirty environmental conditions. Namely, in clean condition, LR ranged from 2.67 to 3.84, while in the dirty one the abatement was slightly lower (from 1.75 to 3.03). Parainfluenza Virus and Human Adenovirus were most resistant compared to the other viruses. The obtained data confirmed Xibornol activity and its use as topic substance for viral inactivation to prevent upper respiratory tract disease.

PMID:35699841 | DOI:10.1007/5584_2022_722

Aging Clin Exp Res. 2022 Jun 14. doi: 10.1007/s40520-022-02155-3. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the relevance of telephone-based cognitive screening tests in clinical practice and research, no specific test assessing executive functioning is available. The present study aimed at standardizing and providing evidence of clinical usability for the Italian telephone-based Frontal Assessment Battery (t-FAB).

METHODS: The t-FAB (ranging 0-12), comprising two subtests, has two versions: one requiring motor responses (t-FAB-M) and the other verbal responses (t-FAB-V). Three hundred and forty-six Italian healthy adults (HPs; 143 males; age range = 18-96 years; education range = 4-23 years) and 40 participants with neurological diseases were recruited. To HPs, the t-FAB was administered along with a set of telephone-based tests: MMSE, verbal fluency (VF), backward digit span (BDS). The in-person version of the FAB was administered to both HPs and clinical groups. Factorial structure, construct validity, inter-rater and test-retest reliability, t-FAB-M vs. t-FAB-V equivalence and diagnostic accuracy were assessed. Norms were derived via Equivalent Scores.

RESULTS: In HPs, t-FAB measures yielded high inter-rater/test-retest reliability (ICC = .78-.94), were internally related (p ≤ .005) and underpinned by a single component, converging with the telephone-based MMSE, VF, BDS (p ≤ .0013). The two t-FAB versions were statistically equivalent in clinical groups (ps of both equivalence bounds < .001). Education predicted all t-FAB scores (p < .001), whereas age only the t-FAB-M score (p ≤ .004). t-FAB scores converge with the in-person FAB in HPs and clinical groups (r_s = .43-.78). Both t-FAB versions were accurate in discriminating HPs from the clinical cohort (AUC = .73-.76).

DISCUSSION: The t-FAB is a normed, valid, reliable and clinically usable telephone-based cognitive screening test to adopt in both clinical and research practice.

PMID:35699839 | DOI:10.1007/s40520-022-02155-3

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