Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

The effect of surface modifications on titanium to enable titanium-porcelain bonding

Objectives. Titanium-ceramic restorations are currently used, despite the pending problem of titanium-ceramic bonding, which has only been partially solved. The surface treatment of the metal proposed by the manufacturer promotes lower bond strength between titanium and porcelain when compared to the conventional metal-ceramic systems. The objective of this study was to evaluate the influence of acid and caustic baths on the bonding characteristics of specific titanium porcelain bonded to cast commercially pure titanium (CP Ti). Methods. Eighty strips of cast CP Ti were obtained in dimensions of 25 mm x 3 mm x 0.5 mm, and divided into eight groups (n=10) which were subjected to surface treatment by immersion in one of the follow solutions-group HF: HF 10%; group NaOH+HF: NaOH 50%-CuSO4 center dot 5H(2)O 10% followed by HF 10%; group HCl: HCl 35%; group NaOH+HCl: NaOH 50%-CuSO4 5H(2)O 10% followed by HCl 35%; group HNO3: HNO3 35%-HF 5%; group NaOH+HNO3: NaOH 50%-CuSO4 center dot 5H(2)O 10% followed by HNO3 35%-HF 5%; control group: treated according to the manufacturer's instructions; NaOH + control group: treated according to the manufacturer's instructions followed by immersion in NaOH 50%-CuSO4 center dot 5H(2)O 10%. Low fusion porcelain (Vita Titankeramik) was applied to the center of one of the sides of each CP Ti sample with dimensions of 8 mm x 3 mm x 1 mm. All groups were submitted to a three-point flexure test. Scanning electron microscopy (SEM) photomicrographs were taken to characterize the failed surfaces at the titanium-porcelain interface. Anova and Tukey's multiple comparison tests were used to analyze the data at a 5% probability level. Results. All groups treated with NaOH 50%-CuSO4 center dot 5H(2)O 10% solution showed significant superior values when compared to groups treated exclusively with acid solution. There were no significant differences between HF (21.2 MPa) and HCl (23.4 MPa) groups; control (25.2 MPa), HCl (23.4 MPa) and HNO3 (26.6 MPa) groups; NaOH + HF (29.9 MPa) and NaOH + HCl (30.8 MPa) groups; NaOH + HNO3 (34.8 MPa) and NaOH + control (32.1 MPa) groups. SEM analysis indicated a combination of cohesive and adhesive fractures in NaOH + HNO3 and NaOH + control groups, while mainly adhesive fractures were found in the other groups. Significance. Bond strength between porcelain and cast CP Ti can be increased by use of a caustic bath prior to porcelain firing. (c) 2007 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.241283

Challenges and opportunities for integrating lake ecosystem modelling approaches

A large number and wide variety of lake ecosystem models have been developed and published during the past four decades. We identify two challenges for making further progress in this field. One such challenge is to avoid developing more models largely following the concept of others (‘reinventing the wheel’). The other challenge is to avoid focusing on only one type of model, while ignoring new and diverse approaches that have become available (‘having tunnel vision’). In this paper, we aim at improving the awareness of existing models and knowledge of concurrent approaches in lake ecosystem modelling, without covering all possible model tools and avenues. First, we present a broad variety of modelling approaches. To illustrate these approaches, we give brief descriptions of rather arbitrarily selected sets of specific models. We deal with static models (steady state and regression models), complex dynamic models (CAEDYM, CE-QUAL-W2, Delft 3D-ECO, LakeMab, LakeWeb, MyLake, PCLake, PROTECH, SALMO), structurally dynamic models and minimal dynamic models. We also discuss a group of approaches that could all be classified as individual based: super-individual models (Piscator, Charisma), physiologically structured models, stage-structured models and trait-based models. We briefly mention genetic algorithms, neural networks, Kalman filters and fuzzy logic. Thereafter, we zoom in, as an in-depth example, on the multi-decadal development and application of the lake ecosystem model PCLake and related models (PCLake Metamodel, Lake Shira Model, IPH-TRIM3D-PCLake). In the discussion, we argue that while the historical development of each approach and model is understandable given its ‘leading principle’, there are many opportunities for combining approaches. We take the point of view that a single ‘right’ approach does not exist and should not be strived for. Instead, multiple modelling approaches, applied concurrently to a given problem, can help develop an integrative view on the functioning of lake ecosystems. We end with a set of specific recommendations that may be of help in the further development of lake ecosystem model

Influence of investment granulometry on the castability and surface roughness of castings obtained with Ni/Cr alloys

The aim of this study was to verify the influence of investment granulometry on the castability and surface roughness of Ni/Cr castings. Four investments were selected for casting according to decreasing order of granulometry: Heat Shock > Micro Fine 1700 > Gilvest HS > Castotal. Castability was verified by means of 40 specimens made with a polyester screen and determined from the number of segments completely filled by the cast alloy. To analyze the roughness, 40 disk-shaped wax patterns were made (15 x 3 mm), and after inclusion in the investments, they were cast and analyzed, before and after polishing (Mitutoyo SJ-201). The measurements were statistically analyzed (1-ANOVA - Tukey - p < 0.05) and it was verified that Heat Shock provided the worst castability with significant difference (p < 0.05) when compared with other investments. This material and Castotal presented similar roughness before and after polishing, with statistically significant difference (p < 0.05) between them and Gilvest and Micro Fine. It was concluded that investments with smaller granulometry provided castings that were more complete, but not smoother

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study

Item does not contain fulltextOBJECTIVE: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs). METHODS: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ-AMC, N = 96), for 7-21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14-28 days after EOT). RESULTS: There were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ-AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ-AMC: 78.1 %; 95 % confidence interval (CI) -14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ-AMC: 69.1 %; 95 % CI -12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ-AMC: 71.8 %; 95 % CI -16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ-AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ-AMC-treated patient; these were unrelated to the study drugs. CONCLUSION: Moxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. Clinical trial: NCT00402727