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

Diabetic retinopathy

Diabetic retinopathy is an important public health concern and is one of the most common causes of blindness. The causes of visual loss in diabetic retinopathy include macular oedema, vitreous haemorrhage, tractional retinal detachment and neovascular glaucoma. With appropriate screening and treatment, more than 90% of visual loss resulting from diabetic retinopathy can be prevented. This article reviews the pathophysiology, clinical signs and course of diabetic retinopathy that may help the general practitioner in screening for diabetic patients with a high risk of diabetic retinopathy. Early detection of diabetic retinopathy and referral to an ophthalmologist is the key to prevention of blindness in the management of diabetic mellitus.link_to_subscribed_fulltex

Myopic macular hole: Response

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Double peel using triamcinolone acetonide and trypan blue in the management of myopic macular hole with retinal detachment: A case-control study

Abstract: Purpose: To evaluate the safety and efficacy of double peel using triamcinolone acetonide (TA) and trypan blue (TB) in removing epiretinal tissues in vitrectomy for myopic macular hole with retinal detachment (MHRD).Methods: Prospective interventional case control study. Patients with myopic MHRD underwent vitrectomy with TA-assisted adherent cortical vitreous (ACV) removal followed by TB-assisted internal-limiting membrane (ILM) peeling and gas tamponade. The results were compared with historical control group without the use of any vital dye or TA.Results: Ten eyes of 10 study cases were compared with nine eyes of nine control cases. Mean axial length was 28.3 ± 1.4 mm and 29.6 ± 2.4 mm and mean follow-up period was 15 months and 42 months for the study group and the control group, respectively. Reattachment rate was 70% in the study group and 44% in the control group. Mean logMAR visual acuity improvement was 0.02 at 6 months and 0.01 at 12 months for the study group (P < 0.05). Transient intraocular pressure rise was observed in seven eyes in the study group and five eyes in the control group. No other complication was noted.Conclusion: Double peel using TA and TB appeared safe and effective in facilitating removal of ACV and ILM in MHRD. It has higher surgical success rate compared with conventional vitrectomy with epiretinal membrane peeling and gas tamponade. © 2010 The Authors. Journal compilation © 2010 Royal Australian and New Zealand College of Ophthalmologists.link_to_subscribed_fulltex

Sulfur trifluoride cation (SF3+) affinities of pyridines determined by the kinetic method: Stereoelectronic effects in the gas phase

Ion/molecule reactions performed by pentaquadrupole mass spectrometry are used to generate cluster ions in which neutral pyridines are bound to the polyatomic cation SF3+. The dimeric ions Py(1)SF(3)(+)Py(2), where Py(1) and Py(2) represent substituted pyridines, are shown to have loosely bound structures by collision-induced dissociation (MS(3)) experiments and by semiempirical AM1 and ab initio RHF/G-S1G(d, p) molecular orbital calculations. In the case of dimers comprised of meta- and/or para-substituted pyridines (unhindered pyridines), there is an excellent Linear correlation between the logarithm of the fragment ion abundance ratio In{[Py(1)(SF3+)]/[Py(SF3+)]} and the proton affinities (PA) of the constituent pyridines. Semiempirical calculations are used to estimate the SF3+ affinities of pyridines which are found to be in the range of 25-31 kcal/mol. The SF3+ affinities show an excellent linear correlation with the proton affinities of the pyridines, and the relationship SF3+ affinity (kcal/mol) = 0.73PA - 135.8 between the two affinities is derived. The effective temperature of the dimeric ions is determined to be 595 +/- 69 K, which is in good agreement with values of around 600 K obtained experimentally in studies on many other systems activated under similar conditions. Ortho-substituted pyridines show lower than expected affinities due to stereoelectronic effects that decrease the cation affinities. Gas-phase stereoelectronic parameters (S-k) are measured from the deviation from the PA correlation and are ordered as 2-MePy (-1.09) < 2,6-diMePy (-1.11) < 2-EtPy (-1.91) < 2,3-diMePy (-2.15) < 2,5-diMePy (-2.25) < 2,4-diMePy (-2.40). Overall, the steric effects are larger than those in the corresponding Cl+-bound dimers but smaller than those in the bulky [OCNCO+] system. Calculations show evidence for agostic bonding that offsets the steric effects in some eases. The eclipsed conformation of 2-methylpyridine/SF3+ adduct is found to be more stable than the staggered form by 0.8 kcal/mol, due to auxiliary agostic bonding between the hydrogen of the ortho methyl substituent and the sulfur atom. Calculations on atomic charge distribution reveal that the positive charge is mainly on the sulfur atom (+1.99) and the charge on the bonding hydrogen S-H-C (+0.07) is considerably lower than that on the other two methyl hydrogens (+0.14), which appears to be a good indication of agostic binding. The most stable form of the 2-ethylpyridine/SF3+ adduct is found when the N-C-1-C-alpha-C-beta dihedral angle is approximately 60 degrees, where the ethyl hydrogen is directed toward the SF3 group via an interesting six-membered ring alignment. The experiments show a remarkably small steric effect in 2,6-dimethylpyridine, probably due to strong agostic bonding enhanced by the buttressing effect that shortens the S-H distance. In addition, the face-to-face interactions of the F atoms and the H atoms further stabilize this form. (C) 1997 American Society for Mass Spectrometry81687

Is scoliosis associated with dance injury in young recreational dancers? A large-scale cross-sectional epidemiological study

The appendix is a pdf file of a dance-related injury questionnaire202106 bcwhNot applicabl

Validation of the Comprehensive Needs Assessment Tool in Patients With Advanced Cancer

publishedVersionPeer reviewe