Dissociation Between the Growing Opioid Demands and Drug Policy Directions Among the U.S. Older Adults with Degenerative Joint Diseases

We aim to examine temporal trends of orthopedic operations and opioid-related hospital stays among seniors in the nation and states of Oregon and Washington where marijuana legalization was accepted earlier than any others. As aging society advances in the United States (U.S.), orthopedic operations and opioid-related hospital stays among seniors increase in the nation. A serial cross-sectional cohort study using the healthcare cost and utilization project fast stats from 2006 through 2015 measured annual rate per 100,000 populations of orthopedic operations by age groups (45–64 vs 65 and older) as well as annual rate per 100,000 populations of opioid-related hospital stays among 65 and older in the nation, Oregon and Washington states from 2008 through 2017. Orthopedic operations (knee arthroplasty, total or partial hip replacement, spinal fusion or laminectomy) and opioid-related hospital stays were measured. The compound annual growth rate (CAGR) was used to quantify temporal trends of orthopedic operations by age groups as well as opioid-related hospital stays and was tested by Rao–Scott correction of χ2 for categorical variables. The CAGR (4.06%) of orthopedic operations among age 65 and older increased (P...) (See full abstract in article

l-Tetrahydropalmatine, an Active Component of Corydalis yanhusuo W.T. Wang, Protects against Myocardial Ischaemia-Reperfusion Injury in Rats

l-Tetrahydropalmatine (l-THP) is an active ingredients of Corydalis yanhusuo W.T. Wang, which protects against acute global cerebral ischaemia-reperfusion injury. In this study, we show that l-THP is cardioprotective in myocardial ischaemia-reperfusion injury and examined the mechanism. Rats were treated with l-THP (0, 10, 20, 40 mg/kg b.w.) for 20 min before occlusion of the left anterior descending coronary artery and subjected to myocardial ischaemia-reperfusion (30 min/6 h). Compared with vehicle-treated animals, the infarct area/risk area (IA/RA) of l-THP (20, 40 mg/kg b.w.) treated rats was reduced, whilst l-THP (10 mg/kg b.w.) had no significant effect. Cardiac function was improved in l-THP-treated rats whilst plasma creatine kinase activity declined. Following treatment with l-THP (20 mg/kg b.w.), subunit of phosphatidylinositol 3-kinase p85, serine473 phosphorylation of Akt and serine1177 phosphorylation of endothelial NO synthase (eNOS) increased in myocardium, whilst expression of inducible NO synthase (iNOS) decreased. However, the expression of HIF-1α and VEGF were increased in I30 minR6 h, but decreased to normal level in I30 minR24 h, while treatment with l-THP (20 mg/kg b.w.) enhanced the levels of these two genes in I30 minR24 h. Production of NO in myocardium and plasma, activity of myeloperoxidase (MPO) in plasma and the expression of tumour necrosis factor-α (TNF-α) in myocardium were decreased by l-THP. TUNEL assay revealed that l-THP (20 mg/kg b.w.) reduced apoptosis in myocardium. Thus, we show that l-THP activates the PI3K/Akt/eNOS/NO pathway and increases expression of HIF-1α and VEGF, whilst depressing iNOS-derived NO production in myocardium. This effect may decrease the accumulation of inflammatory factors, including TNF-α and MPO, and lessen the extent of apoptosis, therefore contributing to the cardioprotective effects of l-THP in myocardial ischaemia-reperfusion injury

Outer Membrane Vesicles Derived from Escherichia coli Induce Systemic Inflammatory Response Syndrome

Sepsis, characterized by a systemic inflammatory state that is usually related to Gram-negative bacterial infection, is a leading cause of death worldwide. Although the annual incidence of sepsis is still rising, the exact cause of Gram-negative bacteria-associated sepsis is not clear. Outer membrane vesicles (OMVs), constitutively secreted from Gram-negative bacteria, are nano-sized spherical bilayered proteolipids. Using a mouse model, we showed that intraperitoneal injection of OMVs derived from intestinal Escherichia coli induced lethality. Furthermore, OMVs induced host responses which resemble a clinically relevant condition like sepsis that was characterized by piloerection, eye exudates, hypothermia, tachypnea, leukopenia, disseminated intravascular coagulation, dysfunction of the lungs, hypotension, and systemic induction of tumor necrosis factor-α and interleukin-6. Our study revealed a previously unidentified causative microbial signal in the pathogenesis of sepsis, suggesting OMVs as a new therapeutic target to prevent and/or treat severe sepsis caused by Gram-negative bacterial infection

Ultrasonic intensification as a tool for enhanced microbial biofuel yields

peer-reviewedUltrasonication has recently received attention as a novel bioprocessing tool for process intensification in many areas of downstream processing. Ultrasonic intensification (periodic ultrasonic treatment during the fermentation process) can result in a more effective homogenization of biomass and faster energy and mass transfer to biomass over short time periods which can result in enhanced microbial growth. Ultrasonic intensification can allow the rapid selective extraction of specific biomass components and can enhance product yields which can be of economic benefit. This review focuses on the role of ultrasonication in the extraction and yield enhancement of compounds from various microbial sources, specifically algal and cyanobacterial biomass with a focus on the production of biofuels. The operating principles associated with the process of ultrasonication and the influence of various operating conditions including ultrasonic frequency, power intensity, ultrasonic duration, reactor designs and kinetics applied for ultrasonic intensification are also described

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

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