DataSheet1_Cost-effectiveness analysis of first-line tislelizumab plus chemotherapy for recurrent or metastatic nasopharyngeal cancer.PDF

Introduction: The RATIONALE-309 trial confirmed the significant efficacy and safety of tislelizumab plus chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC). However, the economic benefits of this regimen are unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding tislelizumab to chemotherapy for R/M NPC from the perspective of the Chinese healthcare system.Methods: A Markov model was established to simulate the costs and outcomes of tislelizumab plus chemotherapy versus chemotherapy. The survival data came from the RATIONALE-309 trial. Only direct medical costs were considered, and utility values were referred to the literature. The incremental cost-effectiveness ratio (ICER) was used as the main outcome measure. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. Additionally, subgroup analyses were performed.Results: The basic analysis showed that the cost of tislelizumab plus chemotherapy ($33,693) was$17,711 higher than that of chemotherapy ($15,982), but it also gained 1.05 QALYs more (2.72 QALYs vs. 1.67 QALYs), with an ICER of$16,859/QALY, which was lower than the willing-to-pay (WTP) of $36,289/QALY. The factors that most influenced the model were the utility of PD, the cost of tislelizumab, and the risk of platelet count decreased in tislelizumab plus chemotherapy group. The subgroup analysis also demonstrated that tislelizumab plus chemotherapy was cost-effective in the whole population regardless of EBV DNA level and PD-L1 expression level.Conclusion: Compared with chemotherapy alone, tislelizumab plus chemotherapy was cost-effective for the treatment of R/M NPC in China.</p

Characteristics of the included case-control studies on the MTHFR C677T polymorphism in cervical lesions.

<p>Abbreviations: HWE, Hardy-Weinberg Equilibrium; NA, not available; NS, not significant; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; ICC, invasive cervical cancer; SIL, squamous intra-epithelial lesion.</p

FUNCTIONAL EXERCISE ON PATIENTS AFTER SPORTS MENISCUS INJURY

ABSTRACT Introduction Knee meniscus injury is a common sports injury, and minimally invasive surgery under knee arthroscopy has become an ideal method to treat meniscus injuries. This surgery rehabilitation has been improved, and several studies on the effects of functional exercise in the range of treatment are still inconclusive. Objective Study the functional exercise rehabilitation effects in patients after sports meniscus injury. Methods Twenty patients with meniscus-medial injury being operated on were selected, including eight men and 12 women. They were randomly divided into neuromuscular and strength training groups (11). Signs and symptoms were assessed before and eight weeks after treatment. JOA score indices and gait tests were compared. The impact of rehabilitation differences was evaluated in each group. Results Eight weeks after rehabilitation in both groups, the scores of the strength training group were higher than the neuromuscular group; the difference between the groups was statistically significant (P</div

Forest plot describing the association between the A1298C polymorphism and the risk of cervical lesions.

<p>(A) Meta-analysis in a random-effects model for AC+CC <i>vs.</i> AA (dominant model). (B) Meta-analysis in a random-effects model for AC <i>vs.</i> AA. (C) Meta-analysis in a random-effects model for CC <i>vs.</i> AA. Each study is shown by the point estimate of the OR (the size of the square is proportional to the weight of each study) and 95% CI for the OR (extending lines).</p

Influence analysis of the summary odds ratio coefficients on the association between the A1298C polymorphism and cervical cancer in dominant model.

<p>The results were computed by omitting each study (left column) in turn. Bars, 95% CIs.</p

Characteristics of the included case-control studies on the MTHFR A1298C polymorphism in cervical lesions.

<p>Abbreviations: HWE: Hardy-Weinberg Equilibrium; NA, not available; NS, not significant; LSIL, low-grade squamous intraepithelial lesion; HSIL, high-grade squamous intraepithelial lesion; ICC, invasive cervical cancer; SIL, squamous intra-epithelial lesion.</p

Methylenetetrahydrofolate Reductase (MTHFR) Polymorphisms and Susceptibility for Cervical Lesions: A Meta-Analysis

<div><h3>Background</h3><p>The association between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and the susceptibility to cervical lesions was unclear. This study was designed to investigate their precise association using a large-scale meta-analysis.</p> <h3>Methods</h3><p>The previous 16 studies were identified by searching PubMed, Embase and CBM databases. The crude odds ratios and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the MTHFR C677T/A1298C polymorphisms and the susceptibility to the cervical lesions. The subgroup analyses were made on the following: pathological history, geographic region, ethnicity, source of controls and source of DNA for genotyping.</p> <h3>Results</h3><p>Neither of the polymorphisms had a significant association with the susceptibility to the cervical lesions in all genetic models. Similar results were found in the subgroup analyses. No association was found between the MTHFR C677T polymorphism and the cervical lesions in the Asia or the America populations though a significant inverse association was found in the Europe population (additive model: <em>P</em> = 0.006, OR = 0.83, 95% CI = 0.72–0.95; CT <em>vs</em>. CC: <em>P</em> = 0.05, OR = 0.83, 95% CI = 0.69–1.00; TT <em>vs</em>. CC: <em>P</em> = 0.05, OR = 0.73, 95% CI = 0.53–1.00). Interestingly, women with the MTHFR A1298C polymorphisms had a marginally increased susceptibility to invasive cancer (ICC) when compared with no carriers but no statistically significant difference in the dominant model (<em>P</em> = 0.06, OR = 1.21, 95% CI = 0.99–1.49) and AC <em>vs</em>. AA (<em>P</em> = 0.09, OR = 1.21, 95% CI = 0.97–1.51).</p> <h3>Conclusions</h3><p>The MTHFR C677T and A1298C polymorphisms may not increase the susceptibility to cervical lesions. However, the meta-analysis reveals a negative association between the MTHFR C677T polymorphisms and the cervical lesions, especially in the European populations. The marginal association between the MTHFR A1298C polymorphisms and the susceptibility to cervical cancer requires a further study.</p> </div

Conformation and Orientation of Antimicrobial Peptides MSI-594 and MSI-594A in a Lipid Membrane

There is significant interest in the development of antimicrobial compounds to overcome the increasing bacterial resistance to conventional antibiotics. Studies have shown that naturally occurring and de novo-designed antimicrobial peptides could be promising candidates. MSI-594 is a synthetic linear, cationic peptide that has been reported to exhibit a broad spectrum of antimicrobial activities. Investigation into how MSI-594 disrupts the cell membrane is important for better understanding the details of this antimicrobial peptide (AMP)’s action against bacterial cells. In this study, we used two different synthetic lipid bilayers: zwitterionic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and anionic 7:3 POPC/1-palmitoyl-2-oleoyl-sn-glycero-3-phospho(1′-rac-glycerol) (POPG). Sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) were used to determine the orientations of MSI-594 and its analogue MSI-594A associated with zwitterionic POPC and anionic 7:3 POPC/POPG lipid bilayers. The simulated ATR-FTIR and SFG spectra using nuclear magnetic resonance (NMR)-determined structures were compared with experimental spectra to optimize the bent angle between the N- (1–11) and C- (12–24) termini helices and the membrane orientations of the helices; since the NMR structure of the peptide was determined from lipopolysaccharide (LPS) micelles, the optimization was needed to find the most suitable conformation and orientation in lipid bilayers. The reported experimental results indicate that the optimized MSI-594 helical hairpin structure adopts a complete lipid bilayer surface-bound orientation (denoted “face-on”) in both POPC and 7:3 POPC/POPG lipid bilayers. The analogue peptide, MSI-584A, on the other hand, exhibited a larger bent angle between the N- (1–11) and C- (12–24) termini helices with the hydrophobic C-terminal helix inserted into the hydrophobic region of the bilayer (denoted “membrane-inserted”) when interacting with both POPC and 7:3 POPC/POPG lipid bilayers. These experimental findings on the membrane orientations suggest that both peptides are likely to disrupt the cell membrane through the carpet mechanism

Flow diagram of the study selection process.

<p>Flow diagram of the study selection process.</p

Funnel plot analysis on the detection of the publication bias for the C677T polymorphism.

<p>(A) Meta-analysis in a random-effects model for CT+TT <i>vs.</i> CC (dominant model). (B) Meta-analysis in a random-effects model for CT <i>vs.</i> CC. (C) Meta-analysis in a random-effects model for TT <i>vs</i>. CC. Each point represents an individual study for the indicated association. LogOR, natural logarithm of OR. Perpendicular line denotes the mean effect size.</p