Five-Year Efficacy and Safety of TiNO-Coated Stents Versus Drug-Eluting Stents in Acute Coronary Syndrome: A Meta-Analysis.

(1) Background: Percutaneous coronary interventions (PCI) in patients with acute coronary syndrome (ACS) are performed with titanium-nitride-oxide-coated stents (TiNOSs) or drug-eluting stents (DESs). The initial completion of this prospective systematic literature review (SLR) of prospective randomized controlled trials (RCTs) showed that TiNOSs are non-inferior to DESs in major adverse cardiac event (MACE) rates and present a lower risk of recurrent myocardial infarction (MI) at 1-year follow-up. This iteration of the SLR protocol performs the critical assessment of 5-year follow-up outcomes with clinical validity and generalizability assessments. (2) Methods: The previously described SLR and meta-analysis protocol, per PRISMA, Cochrane methods, and GRADE, was applied to 5-year follow-up outcomes. (3) Results: Three RCTs were eligible, comprising 1620 patients with TiNOS vs. 1123 with DES. The pooled risk ratios (RRs) and 95% confidence intervals were MACE 0.82 [0.68, 0.99], MI 0.58 [0.44, 0.78], cardiac death (CD) 0.46 [0.28, 0.76], ischemia-driven target lesion revascularization (TLR) 1.03 [0.79, 1.33], probable or definite stent thrombosis (ST) 0.32 [0.21, 0.59], and all-cause mortality (TD) 0.84 [0.63, 1.12]. The evidence certainty was high in MACE, CD, MI, and ST, and moderate in TLR and TD. (4) Conclusions: TiNOSs in ACS at 5-year follow-up appear safer than DESs and equally efficacious. The pooled RRs stratified by clinical presentation and stent type will be required to test this meta-analysis's clinical validity and generalize its results to patient populations with varying proportions of clinical presentations and DES options.

Effectiveness and safety of dalbavancin in France: a prospective, multicentre cohort study.

OBJECTIVES: Dalbavancin is a lipoglycopeptide antibiotic approved for the treatment of acute bacterial skin and skin structure infections. However, several studies have suggested that it is used mostly for off-label indications. We aimed to describe the use of dalbavancin in patients who received at least one dose of the antibiotic in France. METHODS: Prospective, observational, multicentre study conducted in France from September 2018 to April 2020. The primary outcome was the clinical response at 30 days after the last dalbavancin dose. RESULTS: A total of 151 patients in 16 centres were included in this study. The main infection sites were bone and joint infections (55.0%), multisite infections (15.9%), and vascular infections (14.6%), and the primary pathogens were coagulase-negative staphylococci (N = 82), Staphylococcus aureus (N = 51), and enterococci (N = 27). Most patients (71.5%) received three previous antibiotic treatments. The number of dalbavancin injections per patient was 1 in 26 patients (17.2%), 2 in 95 patients (62.9%), 3 in 17 patients (11.3%), and more than 3 in 13 patients (8.6%), with a mean cumulative dose of 3089 ± 1461 mg per patient. Among the 129 patients with a complete follow-up, clinical success was achieved in 119 patients (92.2%). At least 1 adverse event was reported in 67 patients (44.4%), including 12 (7.9%) patients with dalbavancin-related adverse events. CONCLUSIONS: The results of the study showed that dalbavancin is used mostly for off-label indications and in heavily pretreated patients in France. The clinical response at 30 days after the last dose was favourable in most patients, with a good safety profile.

Efficacy and Safety of TiNO-Coated Stents versus Drug-Eluting Stents in Acute Coronary Syndrome: Systematic Literature Review and Meta-Analysis.

(1) Background: Practice guidelines define drug-eluting stents (DES) as the standard of care in coronary percutaneous coronary intervention (PCI), including in acute coronary syndrome (ACS). This is based on comparisons with bare-metal stents (BMS). However, non-drug-eluting titanium-nitride-oxide-coated stents (TiNOS) have not been taken into account. The objective of this study is to determine whether TiNOS can be used as an alternative to DES in ACS. (2) Methods: A prospective systematic literature review (SLR), conducted according to the PRISMA guidelines, was performed, wherein multiple literature databases from 2018 and 2022 were searched. Prospective, randomised, controlled trials comparing outcomes after PCI with TiNOS vs. DES in any coronary artery disease (CAD) were searched. Clinical outcomes were meta-analytic pooled risk ratios (RR) of device-oriented Major Adverse Cardiac Events (MACE) and their components. The analysis stratified outcomes reported with ACS-only vs. ACS jointly with chronic coronary syndrome (CCS). (3) Results: Five RCTs were eligible, comprising 1855 patients with TiNOS vs. 1363 with DES at a 1-year follow-up. Three enrolled patients presented with ACS only and two with ACS or CCS. The latter accounted for most of the patients. The one-year pooled RRs in those three RCTs were as follows: MACE 0.93 [0.72, 1.20], recurrent myocardial infarction (MI) 0.48 [0.31, 0.73], cardiac death (CD) 0.66 [0.33, 1.31], clinically driven target lesion revascularization (TLR) 1.55 [1.10, 2.19], and stent thrombosis (ST) 0.35 [0.20, 0.64]. Those results were robust to a sensitivity analysis. The evidence certainty was high in MACE and moderate or low in the other endpoints. (4) Conclusions: TiNOS are a non-inferior and safe alternative to DES in patients with ACS.

Do Different Sutures with Triclosan Have Different Antimicrobial Activities? A Pharmacodynamic Approach.

(1) Background: Three antimicrobial absorbable sutures have different triclosan (TS) loads, triclosan release kinetics and hydrolysis times. This in vitro study aims to analyse and compare their antimicrobial pharmacodynamics. (2) Methods: Time-kill assays were performed with eight triclosan-susceptible microorganisms common in surgical site infections (SSIs) and a segment of each TS. Microbial concentrations were measured at T0, T4, T8 and T24 h. Similar non-triclosan sutures (NTS) were used as controls. Microbial concentrations were plotted and analysed with panel analysis. They were predicted over time with a double-exponential model and four parameters fitted to each TS × microorganism combination. (3) Results: The microbial concentration was associated with the triclosan presence, timeslot and microorganism. It was not associated with the suture material. All combinations shared a common pattern with an early steep concentration reduction from baseline to 4-8 h, followed by a concentration up to a 24-h plateau in most cases with a mild concentration increase. (4) Conclusions: Microorganisms seem to be predominantly killed by contact or near-contact killing with the suture rather than the triclosan concentration in the culture medium. No significant in vitro antimicrobial pharmacodynamic difference between the three TS is identified. Triclosan can reduce the suture microbial colonisation and SSI risk.

Do Triclosan Sutures Modify the Microbial Diversity of Surgical Site Infections? A Systematic Review and Meta-Analysis.

Randomised controlled clinical trials (RCTs) report a lower incidence rate of surgical site infections (SSIs) with triclosan sutures (TSs) compared with non-triclosan sutures (NTSs). Do triclosan sutures modify the microbial diversity of culture-confirmed SSIs (ccSSIs)? If so, this would support the association between TS antimicrobial activity and the SSI incidence rate. This prospective systematic literature review (PROSPERO CRD42019125099) was conducted according to PRISMA. RCTs that compared the incidence of SSIs with TSs and NTSs and reported microbial counts from SSI cultures per suture group were eligible. The microbial species were grouped by genus, and the association between genera and sutures was tested. The pooled relative risk (RR) of ccSSIs was also calculated. Twelve RCTs were eligible. No publication bias was identified. The microorganism count was 180 in 124 SSIs with TSs versus 246 in 199 SSIs with NTSs. No significant difference in microbial diversity was found, but statistical power was low for test results to support or challenge the association between the antimicrobial activity of TSs and the reduced rate of SSIs. The RR of the ccSSIs was significant and consistent with comprehensive meta-analyses. The certainty of the pooled RR was moderate.

How Long Do Implanted Triclosan Sutures Inhibit Staphylococcus aureus in Surgical Conditions? A Pharmacological Model.

(1) Background: Sutures with triclosan (TS) are used to reduce the risk of surgical site infections (SSI), but most clinical trials are inconclusive. The traceability of SSI risk to antimicrobial activity in operated tissues is needed. (2) Objectives: This study aimed to predict triclosan antistaphylococcal activity in operated tissues. (3) Methods: Three TS were exposed to static water for 30 days, and triclosan release was recorded. Polyglactin TS explanted from sheep seven days after cardiac surgery according to 3Rs provided ex vivo acceleration benchmarks. TS immersion up to 7 days in ethanol-water cosolvency and stirring simulated tissue implantation. Controls were 30-day immersion in static water. The release rate over time was measured and fitted to a predictive function. Antistaphylococcal activity and duration were measured by time-kill analysis with pre-immersed polyglactin TS. (4) Fifteen to 60-fold accelerated in vitro conditions reproduced the benchmarks. The rate prediction with double-exponential decay was validated. The antistaphylococcal activity was bactericidal, with TS pre-immersed for less than 12 h before then S. aureus began to grow. The residual triclosan level was more than 95% and played no detectable role. (5) Conclusions: Polyglactin, poliglecaprone, and polydioxanone TS share similar triclosan release functions with parametric differences. Polyglactin TS is antistaphylococcal in surgical conditions for 4 to 12 h.

Metabolic syndrome and smoking are independent risk factors of male idiopathic infertility.

BACKGROUND: Overweight and obesity are known to impact male fertility and are commonly associated with abdominal obesity and metabolic disorders. The association between abdominal obesity or metabolic syndrome with male reproduction has not been fully investigated. Moreover, many factors may interfere with the evaluation of the impact of metabolic syndrome on male fertility. Thus, tobacco is known to alter the spermatic parameters and phenomena linking smoking with metabolic syndrome are therefore complex. The main objective of this study has been to investigate the potential association of metabolic syndrome with male idiopathic infertility given smoking status. MATERIEL AND METHODS: The data of this study concerned infertile (n = 96) and fertile (n = 100) men under 45 years of age who have been recruited in the ALIFERT case-control study. Body mass index and waist circumference were measured. Serum triglycerides, cholesterol (total, high density lipoprotein, and low density lipoprotein cholesterol) and fasting blood glucose were assayed. Metabolic syndrome has been diagnosed in the presence of at least three of the following criteria: increased waist circumference, high triglycerides, fasting glucose or arterial blood pressure and low high density lipoprotein cholesterol. RESULTS: The present study reports that infertile men are in poorer health condition compared to fertile men and are more often smokers. The results of this study suggested metabolic syndrome and smoking to be independent risk factor for idiopathic infertility. CONCLUSIONS: Metabolic syndrome and smoking should systematically be checked at the beginning of medical care in infertile males and personal and multifaceted coaching should be proposed to deal jointly with smoking and metabolic disorders. TRIAL REGISTRATION: NCT01093378 ALIFERT. Registered: March 25, 2010.

CONTEXTE GÉNÉRAL: Le surpoids et l'obésité sont connus pour avoir un impact sur la fertilité masculine et sont souvent associés à l'obésité abdominale et aux désordres métaboliques. L'association entre l'obésité abdominale ou le syndrome métabolique et les fonctions de reproduction masculine n'est. pas totalement élucidé. De plus, de nombreux facteurs confondants peuvent interférer avec la fertilité masculine. Ainsi, le tabac est. connu pour altérer les paramètres spermatiques et des mécanismes complexes lient le tabagisme au syndrome métabolique. L'objectif principal de cette étude est. d'étudier l'association potentielle entre le syndrome métabolique et l'infertilité idiopathique masculine, compte tenu du statut tabagique. MATÉRIEL ET MÉTHODES: Les données de cette étude portent sur des hommes de moins de 45 ans infertiles (n = 96) et fertiles (n = 100) qui ont été recrutés dans le cadre de l'étude cas-témoins ALIFERT. L'indice de masse corporelle et le tour de taille ont été mesurés. Les triglycérides sériques, le cholestérol (total, high density lipoprotein, low density lipoprotein) et la glycémie à jeun ont été analysés. Le syndrome métabolique a été diagnostiqué en présence d'au moins trois des critères suivants: un tour de taille accru, des triglycérides élevés, une glycémie à jeun ou une tension artérielle élevée et un faible taux de cholestérol « high density lipoprotein ¼. RÉSULTATS: Cette étude rapporte que les hommes infertiles sont en moins bonne santé que les hommes fertiles et sont plus souvent des fumeurs. Les résultats de cette étude suggèrent que le syndrome métabolique et le tabagisme sont des facteurs de risque indépendants de l'infertilité idiopathique. CONCLUSIONS: Le syndrome métabolique et le tabagisme devraient être systématiquement contrôlés au début des soins médicaux chez les hommes infertiles et un accompagnement personnel et multidisciplinaire devrait être proposé pour traiter conjointement le tabagisme et les troubles du métabolisme.

Meta-analysis of prevention of surgical site infections following incision closure with triclosan-coated sutures: robustness to new evidence.

BACKGROUND: A systematic literature review (SLR) and meta-analysis of surgical site infections (SSIs) after surgical incision closure with triclosan-coated sutures (TS) compared with non-antibacterial coated sutures (NTS) published previously by the authors suggested that fewer SSIs occurred in the TS study arm. However, the results were vulnerable to the removal of one key randomized controlled trial (RCT) because of insufficient data. Furthermore, recently published RCTs highlighted the need for an update of the SLR to challenge the robustness of results. METHODS: The protocol for the new SLR included more stringent tests of robustness than used initially and the meta-analysis was updated with the results of two new RCTs as well as the count of patients and SSIs by U.S. Centers for Disease Control and Prevention (CDC) incision class. RESULTS: The updated SLR included 15 RCTs with 4,800 patients. No publication bias was suggested in the analysis. The predominant effect estimated a relative risk of 0.67 (95% CI: 0.54-0.84, p=0.00053) with an overall lower frequency of SSI in the TS arm than in the NTS arm. RESULTS were robust to sensitivity analysis. CONCLUSIONS: The two additional peer-reviewed double-blind RCTs of this update confirmed the predominant effect found in the authors' previous meta-analysis and established the robustness of conclusions that were lacking previously. This SLR and meta-analysis showed that the use of triclosan antimicrobial sutures reduced the incidence of SSI after clean, clean-contaminated, and contaminated surgery. The two additional peer-reviewed double blind RCTs reinforced the evidence level of this SLR (CEBM level 1a).

Is there an evidence-based argument for embracing an antimicrobial (triclosan)-coated suture technology to reduce the risk for surgical-site infections?: A meta-analysis.

BACKGROUND: It has been estimated that 750,000 to 1 million surgical-site infections (SSIs) occur in the United States each year, causing substantial morbidity and mortality. Triclosan-coated sutures were developed as an adjunctive strategy for SSI risk reduction, but a recently published systematic literature review and meta-analysis suggested that no clinical benefit is associated with this technology. However, that study was hampered by poor selection of available randomized controlled trials (RCTs) and low patient numbers. The current systematic review involves 13 randomized, international RCTs, totaling 3,568 surgical patients. METHODS: A systematic literature search was performed on PubMed, Embase/Medline, Cochrane database group (Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Health Economic Evaluations Database/Database of Health Technology Assessments), and www.clinicaltrials.gov to identify RCTs of triclosan-coated sutures compared with conventional sutures and assessing the clinical effectiveness of antimicrobial sutures to decrease the risk for SSIs. A fixed- and random-effects model was developed, and pooled estimates reported as risk ratio (RR) with a corresponding 95% confidence interval (CI). Publication bias was assessed by analyzing a funnel plot of individual studies and testing the Egger regression intercept. RESULTS: The meta-analysis (13 RCTs, 3,568 patients) found that use of triclosan antimicrobial-coated sutures was associated with a decrease in SSIs in selected patient populations (fixed effect: RR = 0.734; 95% CI: 0.590-0.913; P = .005; random-effect: RR = 0.693; 95% CI: 0.533-0.920; P = .011). No publication bias was detected (Egger intercept test: P = .145). CONCLUSION: Decreasing the risk for SSIs requires a multifaceted "care bundle" approach, and this meta-analysis of current, pooled, peer-reviewed, randomized controlled trials suggests a clinical effectiveness of antimicrobial-coated sutures (triclosan) in the prevention of SSIs, representing Center for Evidence-Based Medicine level 1a evidence.

Prospective multicenter clinical trial of immunosuppressive drug withdrawal in stable adult liver transplant recipients.

UNLABELLED: Lifelong immunosuppression increases morbidity and mortality in liver transplantation. Discontinuation of immunosuppressive drugs could lessen this burden, but the safety, applicability, and clinical outcomes of this strategy need to be carefully defined. We enrolled 102 stable liver recipients at least 3 years after transplantation in a single-arm multicenter immunosuppression withdrawal trial. Drugs were gradually discontinued over a 6 to 9-month period. The primary endpoint was the development of operational tolerance, defined as successful immunosuppressive drug cessation maintained for at least 12 months with stable graft function and no histopathologic evidence of rejection. Out of the 98 recipients evaluated, 57 rejected and 41 successfully discontinued all immunosuppressive drugs. In nontolerant recipients rejection episodes were mild and resolved over 5.6 months (two nontolerant patients still exhibited mild gradually improving cholestasis at the end of follow-up). In tolerant recipients no progressive clinically significant histological damage was apparent in follow-up protocol biopsies performed up to 3 years following drug withdrawal. Tolerance was independently associated with time since transplantation (odds ratio [OR] 1.353; P = 0.0001), recipient age (OR 1.073; P = 0.009), and male gender (OR 4.657; P = 0.016). A predictive model incorporating the first two clinical variables identified subgroups of recipients with very high (79%), intermediate (30%-38%), and very low (0%) likelihood of successful withdrawal. CONCLUSION: When conducted at late timepoints after transplantation, immunosuppression withdrawal is successful in a high proportion of carefully selected liver recipients. A combination of clinical parameters could be useful to predict the success of this strategy. Additional prospective studies are now needed to confirm these results and to validate clinically applicable diagnostic biomarkers.

Cost-effectiveness and budget impact of obesity surgery in patients with type 2 diabetes in three European countries(II).

BACKGROUND: This study aimed to establish a payer-perspective cost-effectiveness and budget impact model of adjustable gastric banding (AGB) and gastric bypass (GBP) vs. conventional treatment (CT) in patients with a body mass index (BMI) > or = 35 kg x m(-2) and type 2 diabetes mellitus (T2DM) in Austria, Italy, and Spain. METHODS: A health economics model described in a previous publication was applied to resource utilization and cost data in AGB, GBP, and CT from Austria, Italy, and Spain in 2009. RESULTS: The base case time scope is 5 years; the annual discount rate for utilities and costs is 3.5%. In Austria and Italy, both AGB and GBP are cost-saving and are thus dominant in terms of incremental cost-effectiveness ratio compared to CT. In Spain, AGB and GBP yield a moderate cost increase but are cost-effective, assuming a willingness-to-pay threshold of 30,000 euro per quality adjusted life-year. Under worst-case analysis, AGB and GBP remain cost-saving or around breakeven in Austria and Italy and remain cost-effective in Spain. CONCLUSION: In patients with T2DM and BMI > or = 35 kg x m(-2) at 5-year follow-up vs. CT, AGB and GBP are not only clinically effective and safe but represent satisfactory value for money from a payer perspective in Austria, Italy, and Spain.

Cost-effectiveness and budget impact of obesity surgery in patients with type-2 diabetes in three European countries.

BACKGROUND: We aimed to establish a payer-perspective cost-effectiveness and budget impact (BI) model of adjustable gastric banding (AGB) and gastric bypass (GBP) vs conventional treatment (CT) in patients with BMI > or =35 kg/m(2) and type-2 diabetes T2DM, in Germany, UK and France. METHODS: Clinical evidence was obtained from literature and patient-reported EQ-5D scores given BMI and T2DM status from HODaR. Resource utilization data in AGB, GBP and CT were obtained from quoted publications so as to reflect practice in 2005. CT in each country was based on descriptions in HTA reports or based on co-authors' experience of current practice. Unit costs were obtained from published sources when available, or from co-authors' institutions. A deterministic algorithm with cost and utility discounting, enabled selection of inputs independently throughout the time scope for each of the 3 treatments, and included mean BMI, amounts of resources and unit costs. RESULTS: The base case time-scope was 5 years, and the annual discount rate for utilities and costs was 3.5%. Compared to CT, GBP yielded +80.8 kg/m(2).years, +2.6 T2DM-free-years and +1.34 QALYs. AGB yielded +57.8 kg/m(2).years, +2.5 T2DM-free-years and +1.03 QALYs. In Germany and France, both GBP and AGB yielded a cost decrease, and were thus dominant in terms of ICER compared to CT. In the UK, GBP and AGB yielded a cost increase, but were cost-effective. CONCLUSION: In patients with T2DM and BMI > or =35 kg/m(2), AGB and GBP are effective at 5-year follow-up in cost-saving in Germany and France, and are cost-effective in the UK with a moderate BI vs CT.