Cost-effectiveness of full and partial opioid agonists for opioid use disorder in outpatient settings: United States healthcare sector perspective.

INTRODUCTION: Studies show that medications for opioid use disorder (MOUD) reduce illicit opioid use, emergency healthcare services, opioid-related overdose, and death. However, few studies have investigated the long-term cost-effectiveness of MOUD in office-based opioid treatment (OBOT) and opioid treatment program (OTP) settings. We aimed to estimate the cost, utility, quality-adjusted life years gained (QALYs), and incremental cost-effectiveness ratios (ICERs) of three MOUD compared to each other and counseling without medication from a US healthcare sector perspective. METHODS: Our study developed a Markov model to conduct a cost-effectiveness analysis of counseling and three MOUD in the OBOT and OTP settings: sublingual buprenorphine/naloxone (BUPNX), buprenorphine extended-release (XR-BUP) injection, and oral methadone. The model included five health states representing combinations of receiving or off treatment while either using or not actively using illicit opioids, and death. The cycle length was one month; the time-horizon was ten years. The study obtained model inputs from systematic reviews of published literature and public data. A 3 % annual discount rate was applied to cost and utility calculation. The primary outcomes included total costs, life-years (LYs), QALYs, and ICERs. We also conducted a scenario analysis using a hypothetical OBOT outpatient setting with methadone. RESULTS: In the base-case OBOT setting, the total costs and QALYs, respectively, were counseling $22,848, 5.60; BUPNX $29,875, 5.82; and XR-BUP $63,936, 5.87. ICERs were $32,345/QALY (BUPNX vs. counseling) and $625,858/QALY (XR-BUP vs BUPNX). In the OTP setting, the total costs of counseling, methadone, BUPNX, and XR-BUP were $20,124, $27,000, $33,500, and $75,272, respectively. QALYs of methadone were 5.86. QALYs of counseling, BUPNX, and XR-BUP remained the same as in the OBOT setting. Incremental ICERs were $26,714/QALY (methadone vs counseling) and $3,337,623/QALY (XR-BUP vs methadone). BUPNX was dominated by methadone. In the scenario analysis, BUPNX was also dominated by methadone. CONCLUSIONS: Outpatient MOUD resulted in important gains in quality of life and life expectancy. In both OBOT and OTP settings, XR-BUP was not cost-effective. BUPNX was cost-effective in the OBOT setting, while it was dominated by methadone in the OTP setting. The cost-effectiveness of BUPNX and XR-BUP could be enhanced if the costs of these medications were reduced.

Biocompatible liquid-type carbon nanodots (C-paints) as light delivery materials for cell growth and astaxanthin induction of Haematococcus pluvialis.

In this study, we aimed to demonstrate the feasibility of the application of biocompatible liquid type fluorescent carbon nanodots (C-paints) to microalgae by improving microalgae productivity. C-paints were prepared by a simple process of ultrasound irradiation using polyethylene glycol (PEG) as a passivation agent. The resulting C-paints exhibited a carbonyl-rich surface with good uniformity of particle size, excellent water solubility, photo-stability, fluorescence efficiency, and good biocompatibility (<10.0 mg mL-1 of C-paints concentration). In the practical application of C-paints to microalgae culture, the most effective and optimized condition leading to growth promoting effect was observed at a C-paints concentration of 1.0 mg mL-1 (>20% higher than the control cell content). A C-paints concentration of 1-10.0 mg mL-1 induced an approximately >1.8 times higher astaxanthin content than the control cells. The high light delivery effect of non-cytotoxic C-paints was applied as a stress condition for H. pluvialis growth and was found to play a major role in enhancing productivity. Notably, the results from this study are an essential approach to improve astaxanthin production, which can be used in various applications because of its therapeutic effects such as cancer prevention, anti-inflammation, immune stimulation, and treatment of muscle-soreness.

Enhancement of astaxanthin production by Haematococcus pluvialis using magnesium aminoclay nanoparticles.

Improving the content and production of high-value ketocarotenoid pigments is critical for the commercialization of microalgal biorefineries. This study reported the use of magnesium aminoclay (MgAC) nanoparticles for enhancement of astaxanthin production by Haematococcus pluvialis in photoautotrophic cultures. Addition of 1.0 g/L MgAC significantly promoted cellular astaxanthin biosynthesis (302 ± 69 pg/cell), presumably by inducing tolerable oxidative stress, corresponding to a 13.7-fold higher production compared to that in the MgAC-untreated control (22 ± 2 pg/cell). The lipid content and cell size of H. pluvialis improved by 13.6- and 2.1-fold, respectively, compared to that of the control. Despite reduced cell numbers, the overall astaxanthin production (10.3 ± 0.4 mg/L) improved by 40% compared to the control (7.3 ± 0.6 mg/L), owing to improved biomass production. However, an MgAC dosage above 1.0 g/L inhibited biomass production by inducing electrostatic cell wall destabilization and aggregation. Therefore, MgAC-induced stimulation of algae varies widely based on their morphological and physiological characteristics.

Recovery of Astaxanthin-Containing Oil from Haematococcus pluvialis by Nano-dispersion and Oil Partitioning.

The feasibilities of cell disruption by homogenization-assisted high-pressure nano-dispersion and recovery of astaxanthin-containing oil by oil partitioning in oil-acetone-water solution were examined. The total fatty acid content of Haematococcus pluvialis was 414.6 mg/g cell, and the astaxanthin content was 4.4% of oil. Extra oil was added to the solution in order to recover oil through instability of dispersion status instead of solvent evaporation. A total amount of energy of 0.34 kWh/L was consumed for acetone evaporation at 50 °C, whereas fully 1.86 kWh/L of energy for water evaporation was consumed. When soybean oil was added to the solution after partial acetone evaporation, the oil-recovery yield was 97.8%, while the yield after full evaporation was 97.6% in 10-g/L solution. However, the energy consumed for partial evaporation (0.29 kWh/L) was much lower than that for full evaporation (0.40 kWh/L). When H. pluvialis oil was added to the solution after partial evaporation, the oil-recovery yield decreased to 90.6% due to the impurity of crude H. pluvialis oil in 10-g/L solution. Methods such as refining of H. pluvialis oil, increase of microalgae dosage for cell disruption, and increase of the injection amount of extra oil can help to enhance oil recovery.

Rapid induction of edible lipids in Chlorella by mild electric stimulation.

In this work, a new stress-based method for rapid induction of triacylglycerol (TAG) and total and polyunsaturated fatty acid accumulations in Chlorella sp. by mild electric stimulation is presented. When a cathodic current of 31 mA (voltage: 4 V) was applied to the algal cells for 4 h, the TAG content of the electro-treated cells was sharply increased to a level 2.1 times that of the untreated control. The contents of the polyunsaturated linoleic (C18:2n6) and linolenic (C18:3n3) acids in the electro-treated cells were also 36 and 57% higher than those in the untreated cells, respectively. Cyclic voltammetry and various biochemical analyses indicate that TAG and fatty acid formations are electro-stimulated via de novo fatty acid biosynthesis and metabolic transformation in the Chlorella cells.

High-efficiency cell disruption and astaxanthin recovery from Haematococcus pluvialis cyst cells using room-temperature imidazolium-based ionic liquid/water mixtures.

Energy-saving, high-efficiency cell disruption is a critical step for recovery of thermolabile antioxidant astaxanthin from Haematococcus pluvialis cyst cells of rigid cell-wall structure. In this study, as room-temperature green solvents, 10 types of 1-ethyl-3-methylimidazolium ([Emim])-based ionic liquids (ILs) were compared and evaluated for their abilities to disrupt H. pluvialis cyst cells for astaxanthin/lipid extraction. Among the 10 ILs tested, 3 [Emim]-based ILs with HSO4, CH3SO3, and (CF3SO2)2N anions were selected based on astaxanthin/lipid extraction performance and synthesis cost. When pretreated with IL/water mixtures, intact cyst cells were significantly torn, broken or shown to release cytoplasmic components, thereby facilitating subsequent separation of astaxanthin/lipid by hexane. However, excess IL pretreatments at high temperature/IL dosages and longer incubation times significantly deteriorated lipid and/or astaxanthin. Under optimized mild conditions (6.7% (v/v) IL in water solution, 30 °C, 60 min), almost complete astaxanthin recoveries (>99%) along with moderate lipid extractions (∼82%) could be obtained.

Dynamic filtration with a perforated disk for dewatering of Tetraselmis suecica.

Dynamic filtration equipped with a perforated disk was adopted for the first time to dewater and concentrate Tetraselmis suecica, from a typical solution of 2-100 g/L of dense biomass suited for the downstream process. An ultrafiltration membrane, polyethersulfone 150 kDa, was found to best perform in terms of high biomass retention and filtration rate. At 1600 rpm, the highest rotation speed of the disk we tested, plateau permeate flux increased up to 20.2 times higher than those with no rotation; this improvement was attributed to fouling reduction (up to 98%) via distinctively high-shear stress on the membrane surface. Even at a high biomass concentration (100 g/L) where fouling formation was very serious, the heightened shear stress caused high flux to be maintained and fouling resistance to be reduced in an effective way. When trans-membrane pressure was increased in a stepwise manner, flux continuously rose at high rotation speed; at low speed, on the other hand, the limiting flux was observed. The dynamic filtration with the perforated disk, which was an effective high-shear stress generator, was proven to be a promising dewatering means of T. suecica, and especially so for the production of highly concentrated biomass.

Expression of CXCL4 and aquaporin 3 and 10 mRNAs in patients with otitis media with effusion.

PURPOSE: Bacterial infections in children with underdeveloped Eustachian tubes are a major cause of otitis media with effusion (OEM), and persistent effusion in the middle ear in these patients is a major cause of surgical intervention. CXCL4 is associated with bacterial infection, and aquaporins 3 and 10 are associated with water metabolism. This study assessed the expression of mRNAs encoding CXCL-4 and aquaporins 3 and 10 in the effusion of pediatric OME patients, and the association of this expression with clinical manifestations. METHODS: Levels of CXCL4 and aquaporin 3 and 10 mRNA were assayed by real-time RT-PCR in the middle ear effusion of 38 pediatric patients with OME requiring ventilation tube insertion. The relationships of these mRNA levels with the presence of bacteria; concomitant diseases such as allergic rhinitis, sinusitis, and adenoid disease; recurrence of OME; and number of ventilation tube insertions were evaluated. RESULTS: CXCL4 and aquaporin 3 and 10 mRNAs were expressed in middle ear effusion of all OME patients. CXCL-4 mRNA levels were significantly lower when bacteria were present and in patients with concomitant diseases (p<0.05 each). Levels of all three mRNAs were unrelated to OME recurrence or number of ventilation tube insertions (p>0.05 each). The levels of CXCL4 and aquaporin 10 mRNAs were significantly correlated (p<0.05). CONCLUSION: Expression of CXCL4 and aquaporin 3 and 10 mRNAs in middle ear effusion is associated with the pathophysiology of OME. CXCL4 mRNA levels are significantly lower in patients with than without concomitant diseases or bacterial infections.

The complete chloroplast genome of the medicinal plant Angelica decursiva (Apiaceae) in Peucedani Radix.

Angelica decursiva (Miquel) Franchet & Savatier (Apiaceae) has been used as a significant medicinal plant in East Asia. We determined its complete chloroplast genome for the first time in this study. The complete chloroplast was circularized and had a typical quadripartite structure genome of 146 719 bp long including the large single copy region (LSC) of 93 256 bp, the small single copy region (SSC) of 17 497 bp and duplicated inverted regions (IRs) of 17 983 bp each. The total GC content was 37.56% and for the four structures it was 35.98% (LSC), 31.06% (SSC), and 44.83% (for each IR). There were a total of 113 genes, comprising four rRNAs, 29 tRNAs and 80 protein coding genes. In the phylogenetic analysis, A. decursiva was grouped with Seseli montanum. This study may contribute to authenticating the plant's correct use as medicine for health and provide an important genetic resource for phylogeny with related species.

The complete chloroplast genome sequence of Ostericum koreanum (Apiaceae).

Ostericum koreanum Kitagawa is an important herbal medicine, whose taxonomic status has been changed to Angelica reflexa as a new species. This study generated the complete chloroplast genome sequence of O. koreanum, and reconsidered its molecular taxonomic status in Angelica by comparing it with related species. The length of the complete chloroplast genome was 147,282 bp, and there were four structures that included the large single copy region (93,185 bp), the small single copy region (17,663 bp) and the duplicated inverted regions (18,217 bp of each). Based on its phylogenetic trees, O. koreanum was grouped by high bootstrap value with the Angelica species. This result proved that O. koreanum is included in Angelica. Therefore, this chloroplast genome data generated for the first time a valuable genetic resource for the discrimination of herbal materials, phylogeny, and evolution.

The complete chloroplast genome sequence of the medicinal plant, Angelica gigas (Apiaceae).

The complete chloroplast genome sequence of Angelica gigas, a traditional herbal plant used in treating diseases, was obtained by de novo assembly using illumina sequencing data (Illumina Inc., San Diego, CA). The circular molecule of the genome was constructed of four parts, with a size of 146,916 bp in total - a large single copy (LSC) region of 93,118 bp, a small single copy (SSC) region of 17,582 bp and two inverted repeat (IRa and IRb) regions of 18,108 bp each. There were a total of 113 annotated genes, including 80 protein-coding genes, 29 tRNA genes and four rRNA genes. The phylogenetic result acquired through maximum parsimony analysis showed that A. gigas is closely related with A. decursiva and Seseli montanum.

Hydrothermal acid treatment for sugar extraction from Golenkinia sp.

In this study, hydrothermal acid treatment for efficient recovery of sugar from Golenkinia sp. was investigated. The initial glucose and XMG (xylose, mannose, and galactose) contents of a prepared Golenkinia sp. solution (40g/L) were 15.05 and 5.24g/L, respectively. The microalgal cell walls were hydrolyzed, for sugar recovery, by enzymatic saccharification and/or hydrothermal acid treatment. Among the various hydrothermal acid treatment conditions, the most optimal were the 2.0% H2SO4 concentration at 150°C for 15min, under which the glucose- and XMG-extraction yields were 71.7% and 64.9%, respectively. By pH 4.8, 50°C enzymatic hydrolysis after optimal hydrothermal acid treatment, the glucose- and XMG-extraction yields were additionally increased by 8.3% and 0.8%, respectively. After hydrothermal acid treatment, the combination with the enzymatic hydrolysis process improved the total sugar yield of Golenkinia sp. to 75.4%.

An integrated process for microalgae harvesting and cell disruption by the use of ferric ions.

In this study, a simultaneous process of harvesting biomass and extracting crude bio-oil was attempted from wet microalgae biomass using FeCl3 and Fe2(SO4)3 as both coagulant and cell-disrupting agent. A culture solution of Chlorella sp. KR-1 was firstly concentrated to 20 g/L and then proceeded for cell disruption with the addition of H2O2. Optimal dosage were 560 and 1060 mg/L for FeCl3 and Fe2(SO4)3, showing harvesting efficiencies of more than 99%. Optimal extraction conditions were identified via the response surface method (RSM), and the extraction yield was almost the same at 120 °C for both iron salts but FAME compositions after transesterification was found to be quite different. Given iron salts were a reference coagulant in water treatment in general and microalgae harvesting in particular, the present approach of using it for harvesting and oil-extraction in a simultaneous manner can serve as a practical route for the microalgae-derived biodiesel production.

Undetected metallic chopstick stabbed on neck resulting tinnitus and foreign body sensation.

Penetrating neck injuries constitute 5-10% of all trauma cases. These injuries may cause life-threatening suppurative or vascular complications, but the severity and extent of damage depends upon the inflicting object and the involved structures. If significant complications are not expected, then it is best to leave the foreign body embedded and avoid surgical risks. We present a rare case of a foreign body embedded in the neck causing tinnitus and foreign body sensation.

Hydrothermal nitric acid treatment for effectual lipid extraction from wet microalgae biomass.

Hydrothermal acid (combined with autoclaving and nitric acid) pretreatment was applied to Nannochloropsis salina as a cost-effective yet efficient way of lipid extraction from wet biomass. The optimal conditions for this pretreatment were determined using a statistical approach, and the roles of nitric acid were also determined. The maximum lipid yield (predicted: 24.6%; experimental: 24.4%) was obtained using 0.57% nitric acid at 120°C for 30min through response surface methodology. A relatively lower lipid yield (18.4%) was obtained using 2% nitric acid; however, chlorophyll and unsaturated fatty acids, both of which adversely affect the refinery and oxidative stability of biodiesel, were found to be not co-extracted. Considering its comparable extractability even from wet biomass and ability to reduce chlorophyll and unsaturated fatty acids, the hydrothermal nitric acid pretreatment can serve as one direct and promising route of extracting microalgae oil.

Effects of anionic surfactant on extraction of free fatty acid from Chlorella vulgaris.

Microalgal lipid with a high free fatty acid (FFA) content was directly extracted from Chlorella vulgaris, using SDBS, in an acid-catalyzed hot-water extraction process. The total fatty acid content of C. vulgaris was 296.0 mg/g cell. Under the 1.0% sulfuric acid, 0.4% SDBS conditions, the FFA content of the lipid increased to 96.7%, and the lipid-extraction yield was 248.4 mg/g cell. Under the 2.0% sulfuric acid, 0.2% SDBS conditions, the FFA content of the lipid was 96.1%, and the lipid-extraction yield was 266.0mg/g cell. Whereas the FAME content of the microalgal lipid extracted by hexane-methanol was 76.4% at the 10.0% sulfuric acid concentration, the FAME content of the high-FFA microalgal lipid was increased to 70.1% at a sulfuric acid concentration of only 0.1%. By combined sulfuric acid/SDBS treatment, high-FFA microalgal lipid was extracted in large yields; moreover, the amount of catalyst was remarkably reduced in the esterification of FFA.

Effects of molten-salt/ionic-liquid mixture on extraction of docosahexaenoic acid (DHA)-rich lipids from Aurantiochytrium sp. KRS101.

In this study, lipid extraction from Aurantiochytrium sp. was performed using a molten-salt/ionic-liquid mixture. The total fatty acid content of Aurantiochytrium sp. was 478.8 mg/g cell, from which 145 mg/g cell (30.3% of total fatty acids) of docosahexaenoic acid (DHA) was obtained. FeCl3·6H2O showed a high lipid extraction yield (207.9 mg/g cell), when compared with that of [Emim]OAc, which was only 118.1 mg/g cell; notably however, when FeCl3·6H2O was mixed with [Emim]OAc (5:1, w/w), the yield was increased to 478.6 mg/g cell. When lipid was extracted by the FeCl3·6H2O/[Emim]OAc mixture at a 5:1 (w/w) blending ratio under 90 °C, 30 min reaction conditions, the fatty acid content of the extracted lipid was a high purity 997.7 mg/g lipid, with most of the DHA having been extracted (30.2% of total fatty acids). Overall, lipid extraction from Aurantiochytrium sp. was enhanced by the synergistic effects of the molten-salt/ionic-liquid mixture with different ions.

Changes in fatty acid composition of Chlorella vulgaris by hypochlorous acid.

Hypochlorous acid treatment of a microalga, Chlorella vulgaris, was investigated to improve the quality of microalgal lipid and to obtain high biodiesel-conversion yield. Because chlorophyll deactivates the catalyst for biodiesel conversion, its removal in the lipid-extraction step enhances biodiesel productivity. When microalgae contacted the hypochlorous acid, chlorophyll was removed, and resultant changes in fatty acid composition of microalgal lipid were observed. The lipid-extraction yield after activated clay treatment was 32.7 mg lipid/g cell; after NaClO treatment at 0.8% available chlorine concentration, it was 95.2 mg lipid/g cell; and after NaCl electrolysis treatment at the 1 g/L cell concentration, it was 102.4 mg lipid/g cell. While the contents of all of the unsaturated fatty acids except oleic acid, in the microalgal lipid, decreased as the result of NaClO treatment, the contents of all of the unsaturated fatty acids including oleic acid decreased as the result of NaCl electrolysis treatment.

Acid-catalyzed hot-water extraction of docosahexaenoic acid (DHA)-rich lipids from Aurantiochytrium sp. KRS101.

In this study, acid-catalyzed hot-water extraction of docosahexaenoic acid (DHA)-rich lipids from Aurantiochytrium sp. was performed, and its yield-enhancing effects were investigated. The total fatty acid content of the Aurantiochytrium sp. was 482.5mg/g cell, of which 141.7mg/g cell (29.4% of total fatty acids) was DHA. The lipid-extraction yield by acid-catalyzed hot-water treatment was compared with those by organic solvents. Among the various acid-catalyzed hot-water treatment conditions, the most optimal were 1.00% H2SO4 concentration, 100°C, 30min, under which the lipid-extraction yield was 472.4mg/g cell, and most of the DHA was extracted (29.2% of total fatty acids). Acid-catalyzed hot-water extraction treatment markedly improved the lipid-extraction yield of Aurantiochytrium sp.

Analysis of differences in facial nerve dehiscence and ossicular injury in chronic otitis media and cholesteatoma.

CONCLUSION: Facial nerve dehiscence (FND) and ossicular injury occurred more frequently in patients with cholesteatomatous than non-cholesteatomatous otitis media. OBJECTIVE: FND and ossicular injury commonly occur intraoperatively in patients with otitis media, both with and without cholesteatoma. This study was designed to analyze differences in FND and ossicular injury between patients with cholesteatomatous and non-cholesteatomatous otitis media. METHODS: Patients who underwent tympanomastoidectomy due to otitis media from January 2010 to July 2012 were analyzed retrospectively. Clinical features (age, sex, bacteria, and severity of preoperative hearing loss) and intraoperative findings (FND and state of ossicular injury) were compared in patients with cholesteatomatous and non-cholesteatomatous otitis media. RESULTS: Of 212 patients with otitis media, 148 (69.8%) had non-cholesteatomatous and 64 (30.2%) had cholesteatomatous otitis media. Of these groups, 88.6% and 88%, respectively, had positive bacterial cultures. Facial nerve dehiscence was detected in 41 patients (27.7%) with non-cholesteatomatous and 41 (64.0%) with cholesteatomatous otitis media. Dehiscence of the tympanic segment was most frequently observed in both groups. Ossicular injury was detected in 52 (35.1%) and 51 patients (78.1%), respectively. Erosion was most frequent in the incus, followed by the stapes and malleus.