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PloS One 2023Antimicrobial resistance (AMR) threatens health security and the economy worldwide. AMR bacteria can spread across humans, animals, food webs and the environment....
Antimicrobial resistance (AMR) threatens health security and the economy worldwide. AMR bacteria can spread across humans, animals, food webs and the environment. Excessive use of antimicrobials in food-producing animals has been recognised as one of the main drivers of the emergence of resistant bacteria. This study aims to quantify and identify patterns of antimicrobial consumption in food-producing animals in Thailand in a three-year period (2017-2019). Milligrams of active ingredient from total volume of imported and locally manufactured products minus exports were obtained from Thai FDA. Annual population production of food-producing animals in 2017, 2018 and 2019 was compiled and validated through cooperation between the Department of Livestock Development (DLD), Department of Fisheries (DOF). The total amount of antimicrobial consumption for food-producing animals decreased 49.0% over the three-year period from 658.7 mg/PCUThailand in 2017 to 336.3 mg/PCUThailand in 2019. In 2017, the most common antimicrobials used was macrolides which was replaced by aminopenicillins and pleuromutilins in 2019, while tetracyclines was consistently common over the three-year period. Consumption of the WHO Critically Important Antimicrobials (CIA) group declined significantly over this period, from 259.0 in 2017 to 193.2 mg/PCUThailand in 2019 (a 25.4% reduction). Findings from this study were in line with national policies which curtails prudent use of antimicrobials in food-producing animals. The government should maintain the decreasing trend of consumption, in particular of the CIA category. Improving information systems which captures consumption by specific species contributes to precision of interventions to minimise prudent use in each species.
Topics: Animals; Humans; Thailand; Anti-Infective Agents; Anti-Bacterial Agents; Bacteria; Livestock
PubMed: 37104254
DOI: 10.1371/journal.pone.0283819 -
JTCVS Open Dec 2022Enhanced Recovery After Surgery protocols are relatively new in cardiac surgery. Enhanced Recovery After Surgery addresses perioperative analgesia by implementing...
OBJECTIVE
Enhanced Recovery After Surgery protocols are relatively new in cardiac surgery. Enhanced Recovery After Surgery addresses perioperative analgesia by implementing multimodal pain control regimens that include both opioid and nonopioid components. We investigated the effects of an Enhanced Recovery After Surgery protocol at our institution on postoperative outcomes with particular focus on analgesia.
METHODS
Single-center retrospective study comparing perioperative opioid use before and after implementation of an Enhanced Recovery After Surgery protocol at our institution. Subjects were divided into 2 cohorts: Enhanced Recovery After Surgery (study group from year 2020) and pre-Enhanced Recovery After Surgery (control group from year 2018). Baseline and perioperative variables including total opioid use from the day of surgery to postoperative day 5 were collected. Opioid use was calculated as morphine milligram equivalents and compared between the 2 cohorts.
RESULTS
A total of 466 patients were included: 250 in the Enhanced Recovery After Surgery group and 216 in the pre-Enhanced Recovery After Surgery group. Both groups had similar baseline characteristics, but the Enhanced Recovery After Surgery group had significantly more subjects with intravenous drug use history ( < .0001), endocarditis ( < .0001), and liver disease ( = .007) compared with the pre-Enhanced Recovery After Surgery group. Every day from the day of surgery to postoperative day 5, the Enhanced Recovery After Surgery group had significant reduction (57%) in opioid use compared with the pre-Enhanced Recovery After Surgery group. Total opioid use for the entire length of stay was 259 morphine milligram equivalents in the Enhanced Recovery After Surgery group versus 452 morphine milligram equivalents in the pre-Enhanced Recovery After Surgery group ( < .0001). Subgroup analysis of subjects with intravenous drug use history did not demonstrate a significant reduction in opioid use.
CONCLUSIONS
Enhanced Recovery After Surgery protocols with an emphasis on multimodal pain management throughout perioperative care are associated with a significant reduction in the postoperative use of opioid analgesics.
PubMed: 36590721
DOI: 10.1016/j.xjon.2022.08.008 -
Achieving opioid-free discharge following robotic thoracic surgery: A single-institution experience.JTCVS Open Sep 2023Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control and have been associated with decreased opioid requirements....
OBJECTIVES
Enhanced recovery after thoracic surgery (ERATS) protocols use a combination of analgesics for pain control and have been associated with decreased opioid requirements. We investigated the impact of continual ERATS refinement on the incidence of opioid-free discharge.
METHODS
We retrospectively analyzed our prospectively maintained institutional database for elective, opioid-naive robotic thoracoscopic procedures. Demographics, operative outcomes, postoperative opioid dispensed (morphine milligram equivalent), and opioid discharge status were collected. Our primary outcome of interest was factors associated with opioid-free discharge; our secondary objective was to determine the incidence of new persistent opioid users.
RESULTS
In total, 466 patients from our optimized ERATS protocol were included; 309 (66%) were discharged without opioids. However, 34 (11%) of patients discharged without opioids required a prescription postdischarge. Conversely, 7 of 157 patients (11%), never filled their opioid prescriptions given at discharge. Factors associated with opioid-free discharges were nonanatomic resections, mediastinal procedures, minimal pain, and lack of opioid usage on the day of discharge. More importantly, 3.2% of opioid-free discharge patients became new persistent opioid users versus 10.8% of patients filling opioid prescriptions after discharges ( = .0013). Finally, only 2.3% of opioid-naive patients of the entire cohort became chronic opioid users; there was no difference in the incidence of chronic use by opioid discharge status.
CONCLUSIONS
Optimized opioid-sparing ERATS protocols are highly effective in reducing opioid prescription on the day of discharge. We observed a very low rate of new persistent or chronic opioid use in our cohort, further highlighting the role ERATS protocols in combating the opioid epidemic.
PubMed: 37808010
DOI: 10.1016/j.xjon.2023.06.017 -
Biophysical Journal Aug 2021The crowdedness of living cells, hundreds of milligrams per milliliter of macromolecules, may affect protein folding, function, and misfolding. Still, such processes are...
The crowdedness of living cells, hundreds of milligrams per milliliter of macromolecules, may affect protein folding, function, and misfolding. Still, such processes are most often studied in dilute solutions in vitro. To assess consequences of the in vivo milieu, we here investigated the effects of macromolecular crowding on the amyloid fiber formation reaction of α-synuclein, the amyloidogenic protein in Parkinson's disease. For this, we performed spectroscopic experiments probing individual steps of the reaction as a function of the macromolecular crowding agent Ficoll70, which is an inert sucrose-based polymer that provides excluded-volume effects. The experiments were performed at neutral pH at quiescent conditions to avoid artifacts due to shaking and glass beads (typical conditions for α-synuclein), using amyloid fiber seeds to initiate reactions. We find that both primary nucleation and fiber elongation steps during α-synuclein amyloid formation are accelerated by the presence of 140 and 280 mg/mL Ficoll70. Moreover, in the presence of Ficoll70 at neutral pH, secondary nucleation appears favored, resulting in faster overall α-synuclein amyloid formation. In contrast, sucrose, a small-molecule osmolyte and building block of Ficoll70, slowed down α-synuclein amyloid formation. The ability of cell environments to modulate reaction kinetics to a large extent, such as severalfold faster individual steps in α-synuclein amyloid formation, is an important consideration for biochemical reactions in living systems.
Topics: Amyloid; Humans; Kinetics; Parkinson Disease; Protein Folding; alpha-Synuclein
PubMed: 34242594
DOI: 10.1016/j.bpj.2021.06.032 -
Advanced Therapeutics Feb 2021Live biotherapeutic products (LBPs) are an emerging therapeutic modality that are clinically investigated for treating pathogenic infections and inflammatory diseases. A...
Live biotherapeutic products (LBPs) are an emerging therapeutic modality that are clinically investigated for treating pathogenic infections and inflammatory diseases. A major class of LBPs are feces derived microbial consortiums which require numerous process development steps (e.g. separation, purification, blending) to facilitate LBP formulation into oral dosage forms. A subset of these LBPs circumvent the need for continuous fecal processing by batch culture for individual strains of microbes that are rationally defined and combined in the final LBP formulation. Separately, delivery formulations (e.g. polymer encapsulation) are being developed for LBPs to improve storage and intestinal engraftment; however, formulation requires additional manufacturing processes distinct from fecal processing or batch culture. Here, a streamlined approach termed batch culture formulation (BCF) is developed to combine the individual batch culture and formulation processes into a single-step process. Based on a previously described polymeric film formulation that encapsulates LBPs, BCF is shown to reduce the number of required processes to formulate LBP-films without altering LBP phenotype, function, or storage profiles compared to the standard LBP-film formulation approach. Additionally, it is demonstrated that BCF facilitates scaled-fabrication from the milligram to gram scale with predictable loading, highlighting the potential that BCF has for clinical translation.
PubMed: 33709021
DOI: 10.1002/adtp.202000226 -
Micromachines Mar 2022Combined use of thermal analysis techniques can realize complementarity of different characterization methods. Comprehensive thermal analysis with both thermogravimetric...
Combined use of thermal analysis techniques can realize complementarity of different characterization methods. Comprehensive thermal analysis with both thermogravimetric analysis and differential thermal analysis (TG/DTA) can measure not only mass change of a sample but also its temperature change during programmed heating-induced reaction or phase transition processes, thereby obtaining multiaspect thermal information of the material such as dehydration, structural decomposition, phase change and thermal stability. This study proposes and develops a MEMS chip-based TG/DTA microsystem that integrates both programmed heating and detecting elements into a TG chip and a DTA chip to enable the microinstrument performing TG/DTA joint characterization under microscope observation. The TG chip contains a self-heating resonant microcantilever to measure heating-induced mass change of a sample and the DTA chip is with a microheater and a temperature-detecting thermopile integrated on a suspended thermal-insulating diaphragm. Only nanogram and microgram-level samples are needed for the TG and DTA chips, thereby achieving safe measurement to energetic materials such as strong oxidants. The chip-based microinstrument surpasses the state-of-the-art commercial TG/DTA instruments that have, in the long term, suffered from large sample-amount (milligram level) requirements and have been unable to measure energetic materials. Compared with commercial instruments, the chip-based microinstrument is advantageous given its more accurate analysis, much higher heating rate, much smaller instrument volume and much lower power consumption, etc. The microinstrument has been fabricated by using wafer-level MEMS techniques. Testing results show that the mass-detection sensitivity of the TG-chip is as high as 0.45 Hz/pg in air and the temperature sensitivity of the DTA chip achieves 2.9 mV/K under the high heating rate of 25 °C/s. The strong oxidant of KMnO is analyzed with the TG/DTA joint characterization under microscopic observation. At the same time as microscope observation of the thermal decomposition phenomena, two-step thermal decomposition process of KMnO is identified and the thermal decomposition temperatures are obtained. The TG/DTA microinstrument is promising to be applied for study of various materials.
PubMed: 35334737
DOI: 10.3390/mi13030445 -
American Journal of Preventive Medicine Jul 2022Evidence suggests that U.S. dentists prescribe opioids excessively. There are limited national data on recent trends in opioid prescriptions by U.S. dentists. In this...
INTRODUCTION
Evidence suggests that U.S. dentists prescribe opioids excessively. There are limited national data on recent trends in opioid prescriptions by U.S. dentists. In this study, we examined trends in opioid prescribing by general dentists and dental specialists in the U.S. from 2012 to 2019.
METHODS
Dispensed prescriptions for oral opioid analgesics written by dentists were identified from IQVIA Longitudinal Prescription Data from January 2012 through December 2019. Autoregressive integrated moving average and joinpoint regression models described monthly population-based prescribing rates (prescriptions/100,000 individuals), dentist-based prescribing rates (prescriptions/1,000 dentists), and opioid dosages (mean daily morphine milligram equivalents/day). All analyses were performed in 2020.
RESULTS
Over the 8 years, dentists prescribed >87.2 million opioid prescriptions. Population- and dentist-based prescribing rates declined monthly by -1.97 prescriptions/100,000 individuals (95% CI= -9.98, -0.97) and -39.12 prescriptions/1,000 dentists (95% CI= -58.63, -17.65), respectively. Opioid dosages declined monthly by -0.08 morphine milligram equivalents/day (95% CI= -0.13, -0.04). Joinpoint regression identified 4 timepoints (February 2016, May 2017, December 2018, and March 2019) at which monthly prescribing rate trends were often decreasing in greater magnitude than those in the previous time segment.
CONCLUSIONS
Following national trends, dentists became more conservative in prescribing opioids. A greater magnitude of decline occurred post 2016 following the implementation of strategies aimed to further regulate opioid prescribing. Understanding the factors that influence prescribing trends can aid in development of tailored resources to encourage and support a conservative approach by dentists, to prescribing opioids.
Topics: Analgesics, Opioid; Dentists; Drug Prescriptions; Humans; Morphine Derivatives; Practice Patterns, Physicians'
PubMed: 35232618
DOI: 10.1016/j.amepre.2022.01.009 -
Bio-protocol Nov 2022This protocol describes the recombinant expression of proteins in containing phosphoserine (pSer) installed at positions guided by TAG codons. The strains that can be...
This protocol describes the recombinant expression of proteins in containing phosphoserine (pSer) installed at positions guided by TAG codons. The strains that can be used here are engineered with a ∆ genomic knockout to produce pSer internally at high levels, so no exogenously added pSer is required, and the addition of pSer to the media will not affect expression yields. For "truncation-free" expression and improved yields with high flexibility of construct design, it is preferred to use the Release Factor-1 (RF1) deficient strain B95(DE3) ∆ ∆ ∆ , though use of the standard RF1-containing BL21(DE3) ∆ is also described. Both of these strains are serine auxotrophs and will not grow in standard minimal media. This protocol uses rich auto-induction media for streamlined and maximal production of homogeneously modified protein, yielding ~100-200 mg of single pSer-containing sfGFP per liter of culture. Using this genetic code expansion (GCE) approach, in which pSer is installed into proteins during translation, allows researchers to produce milligram quantities of specific phospho-proteins without requiring kinases, which can be purified for downstream in vitro studies relating to phosphorylation-dependent signaling systems, protein regulation by phosphorylation, and protein-protein interactions. Graphical abstract.
PubMed: 36505030
DOI: 10.21769/BioProtoc.4541 -
Anesthesiology Mar 2021The primary goal of this study was to evaluate patterns in acute postoperative pain in a mixed surgical patient cohort with the hypothesis that there would be...
BACKGROUND
The primary goal of this study was to evaluate patterns in acute postoperative pain in a mixed surgical patient cohort with the hypothesis that there would be heterogeneity in these patterns.
METHODS
This study included 360 patients from a mixed surgical cohort whose pain was measured across postoperative days 1 through 7. Pain was characterized using the Brief Pain Inventory. Primary analysis used group-based trajectory modeling to estimate trajectories/patterns of postoperative pain. Secondary analysis examined associations between sociodemographic, clinical, and behavioral patient factors and pain trajectories.
RESULTS
Five distinct postoperative pain trajectories were identified. Many patients (167 of 360, 46%) were in the moderate-to-high pain group, followed by the moderate-to-low (88 of 360, 24%), high (58 of 360, 17%), low (25 of 360, 7%), and decreasing (21 of 360, 6%) pain groups. Lower age (odds ratio, 0.94; 95% CI, 0.91 to 0.99), female sex (odds ratio, 6.5; 95% CI, 1.49 to 15.6), higher anxiety (odds ratio, 1.08; 95% CI, 1.01 to 1.14), and more pain behaviors (odds ratio, 1.10; 95% CI, 1.02 to 1.18) were related to increased likelihood of being in the high pain trajectory in multivariable analysis. Preoperative and intraoperative opioids were not associated with postoperative pain trajectories. Pain trajectory group was, however, associated with postoperative opioid use (P < 0.001), with the high pain group (249.5 oral morphine milligram equivalents) requiring four times more opioids than the low pain group (60.0 oral morphine milligram equivalents).
CONCLUSIONS
There are multiple distinct acute postoperative pain intensity trajectories, with 63% of patients reporting stable and sustained high or moderate-to-high pain over the first 7 days after surgery. These postoperative pain trajectories were predominantly defined by patient factors and not surgical factors.
Topics: Age Factors; Analgesics, Opioid; Cohort Studies; Female; Florida; Humans; Male; Middle Aged; Morphine; Pain, Postoperative; Prospective Studies; Severity of Illness Index; Sex Factors
PubMed: 33449996
DOI: 10.1097/ALN.0000000000003681 -
Female Pelvic Medicine & Reconstructive... Aug 2020The objective of this study was to determine the impact of a multimodal protocol on opiate use and postoperative pain after ambulatory urogynecologic surgery.
OBJECTIVES
The objective of this study was to determine the impact of a multimodal protocol on opiate use and postoperative pain after ambulatory urogynecologic surgery.
METHODS
This was a retrospective cohort study comparing ambulatory urogynecologic surgery patients treated under a standard perioperative pain protocol with those treated under a multimodal perioperative pain protocol. The multimodal protocol consisted of preoperative gabapentin and acetaminophen and postoperative scheduled doses of acetaminophen and nonsteroidal anti-inflammatory drugs. Pain scores were obtained from nursing records and assessed on the Numeric Rating Scale 11 per hospital protocol. All opioid dosages were converted into morphine milligram equivalents using standardized conversion tables.
RESULTS
We treated 109 patients under the standard protocol and 112 under the multimodal protocol. Patients had similar baseline characteristics. Overall, a minority of patients (39%) used postoperative opioids; this was similar in the 2 groups (P=0.45). The 2 groups also were similar with regard to the total postoperative morphine milligram equivalents (P=0.35). Postoperatively, patients treated under the standard protocol had higher mean pain scores (2.2 vs 1.4, P=0.002). Patients treated under the standard protocol were also significantly more likely to report postoperative pain (69%) than those treated under the multimodal protocol (52%; P=0.01), and the multimodal protocol was associated with a 25% lower risk of postoperative pain (risk ratio, 0.75; 95% confidence interval, 0.60-0.94) than the standard protocol.
CONCLUSIONS
Patients infrequently use opiates after ambulatory urogynecologic surgery. The use of a multimodal pain protocol was associated with lower pain scores, and patients in a multimodal pain protocol were more likely to report no pain.
Topics: Acetaminophen; Aged; Ambulatory Surgical Procedures; Analgesics, Non-Narcotic; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Drug Therapy, Combination; Female; Gynecologic Surgical Procedures; Humans; Middle Aged; Pain Management; Pain Measurement; Pain, Postoperative; Perioperative Care; Retrospective Studies
PubMed: 31490849
DOI: 10.1097/SPV.0000000000000775