-
American Journal of Perinatology Aug 2022The objective was to assess temporal trends in postpartum opioid prescribing, opioid use, and pain control satisfaction. (Observational Study)
Observational Study
OBJECTIVE
The objective was to assess temporal trends in postpartum opioid prescribing, opioid use, and pain control satisfaction.
STUDY DESIGN
This is a prospective observational study of postpartum patients who delivered at a large tertiary care center (May 2017-July 2019). Inpatient patients were screened for eligibility; those meeting eligibility criteria who used inpatient opioids were approached for prospective survey participation which probed inpatient and outpatient postpartum pain control. The amount of opioids used during inpatient hospitalization and the amount of opioids prescribed at discharge were obtained from medical records. The primary outcome was the difference in opioid prescribing at discharge over time, measured by (1) the proportion of participants who received an opioid prescription at discharge and (2) for those who received an opioid prescription, the total morphine milligram equivalents of the prescription. Additional outcomes were inpatient and outpatient opioid use and patient-reported satisfaction with postpartum pain control. Trends over time were evaluated using nonparametric tests of trend.
RESULTS
Of 2,503 postpartum patients screened for eligibility, a majority ( = 1,425; 60.8%) did not use an opioid as an inpatient. Over the study period, there was a significant decline in the proportion of patients who used an opioid while inpatient (z-score = - 11.8; < 0.01). Among these participants enrolled in the prospective survey study ( = 494), there was a significant decline over time in the amount of inpatient opioid use (z-score = - 2.4; = 0.02), the proportion of participants who received an opioid prescription upon discharge (z-score = - 8.2; < 0.01), and, when an opioid was prescribed at discharge, the total prescribed morphine milligram equivalents (z-score = - 4.3; < 0.01). Both inpatient and outpatient satisfactions with pain control were unchanged over this time (z-score = 1.1, = 0.27; z-score = 1.1, = 0.29, respectively).
CONCLUSION
In this population, both the frequency and amount of opioid use in the postpartum period declined from 2017 to 2019. This decrease in opioid prescribing was not associated with changes in patient-reported satisfaction with pain control.
KEY POINTS
· From 2017 to 2019, there was a decrease in inpatient and outpatient postpartum opioid use.. · Both the proportion of postpartum patients receiving opioid prescriptions and the amount prescribed decreased.. · Patient satisfaction with postpartum pain control remained unchanged..
Topics: Analgesics, Opioid; Female; Humans; Morphine Derivatives; Opioid-Related Disorders; Pain; Personal Satisfaction; Postpartum Period; Practice Patterns, Physicians'; Prospective Studies
PubMed: 35253120
DOI: 10.1055/a-1788-5894 -
Research Square Jul 2023Prior laboratory work indicates that lower endogenous opioid function is associated with greater analgesic and subjective responses to opioid analgesics. We evaluated...
BACKGROUND
Prior laboratory work indicates that lower endogenous opioid function is associated with greater analgesic and subjective responses to opioid analgesics. We evaluated whether lower preoperative cerebrospinal uid (CSF) levels of the analgesic endogenous opioid β-Endorphin (BE) were associated with increased opioid use after cesarean delivery (CD).
METHODS
We enrolled 136 pregnant women without opioid use or chronic pain who were undergoing CD under regional anesthesia. Preoperatively, participants completed validated pain measures and biospecimens were collected to assess BE levels in plasma and CSF. Postoperatively, pain measures at 48 hours and 2 weeks postpartum were assessed. We evaluated the association between CSF BE levels and total opioid use (in morphine milligram equivalents; MMEs) using linear regression controlling for confounding factors (primary analysis). In secondary analyses, we examined: 1) associations between plasma BE levels and total opioid use, and 2) associations between CSF and plasma BE levels and secondary outcomes (inpatient versus outpatient opioid use, pain intensity).
RESULTS
Participants completed surveys with 100% response rate. The majority were non-Hispanic white (65%), college educated (58%), had private insurance (71%), and had a prior cesarean delivery (69%). Psychiatric diagnoses (depression or anxiety) were common, both currently (22%) and in the past (26%).The median total opioid use across the inpatient and 2-week postpartum follow-up period was 89.1 milligram morphine equivalents (IQR 25-138). Preoperative cerebrospinal uid β-Endorphin levels were not associated with total opioid use (beta = -0.05, SE 0.45, p = 0.64). Similar findings were noted for plasma β-Endorphin levels. cerebrospinal uid β-Endorphin levels were only weakly correlated with plasma β-Endorphin levels (r = 0.30, p < .01). Preoperative cerebrospinal uid and plasma β-Endorphin levels were both positively associated with postpartum pain measures (cerebrospinal uid: at 48 hours, beta = 0.19, SE 0.16, p < 0.05; Plasma: at 48-hours, beta = 0.02, SE 0.03, p = 0.02, and at 2-weeks, beta = 0.27, SE 0.03, p < 0.01).
CONCLUSIONS
Lower preoperative cerebrospinal uid levels of β-Endorphin are not associated with increased opioid analgesic use after scheduled cesarean delivery. It is possible that unassessed variability in baseline opioid receptor sensitivity may have confounded ability to test associations between β-Endorphin levels and opioid use outcomes.
PubMed: 37502834
DOI: 10.21203/rs.3.rs-3125641/v1 -
Science Translational Medicine Apr 2024No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV...
No licensed vaccines or therapies exist for patients infected with Nipah virus (NiV), although an experimental human monoclonal antibody (mAb) cross-reactive to the NiV and Hendra virus (HeV) G glycoprotein, m102.4, has been tested in a phase 1 trial and has been provided under compassionate use for both HeV and NiV exposures. NiV is a highly pathogenic zoonotic paramyxovirus causing regular outbreaks in humans and animals in South and Southeast Asia. The mortality rate of NiV infection in humans ranges from 40% to more than 90%, making it a substantial public health concern. The NiV G glycoprotein mediates host cell attachment, and the F glycoprotein facilitates membrane fusion and infection. We hypothesized that a mAb against the prefusion conformation of the F glycoprotein may confer better protection than m102.4. To test this, two potent neutralizing mAbs against NiV F protein, hu1F5 and hu12B2, were compared in a hamster model. Hu1F5 provided superior protection to hu12B2 and was selected for comparison with m102.4 for the ability to protect African green monkeys (AGMs) from a stringent NiV challenge. AGMs were exposed intranasally to the Bangladesh strain of NiV and treated 5 days after exposure with either mAb (25 milligrams per kilogram). Whereas only one of six AGMs treated with m102.4 survived until the study end point, all six AGMs treated with hu1F5 were protected. Furthermore, a reduced 10 milligrams per kilogram dose of hu1F5 also provided complete protection against NiV challenge, supporting the upcoming clinical advancement of this mAb for postexposure prophylaxis and therapy.
Topics: Animals; Antibodies, Monoclonal; Bangladesh; Chlorocebus aethiops; Glycoproteins; Henipavirus Infections; Nipah Virus; Primates; Clinical Trials, Phase I as Topic
PubMed: 38569014
DOI: 10.1126/scitranslmed.adl2055 -
The Journal of Arthroplasty Jun 2020Total knee arthroplasty (TKA) creates a relatively large degree of nociception, making it a good setting to study variation in pain intensity and pain alleviation. The...
BACKGROUND
Total knee arthroplasty (TKA) creates a relatively large degree of nociception, making it a good setting to study variation in pain intensity and pain alleviation. The purpose of this study is to investigate factors associated with a second prescription of opioid medications within 30 days of primary TKA.
METHODS
Using an insurance database, we studied 1372 people over a 6-year period with no mental health comorbidities including substance misuse and no comorbid pain illness at the time of TKA. Factors associated with a second prescription of opioid medication within 30 days of TKA were sought among patient demographics and the overall prescription morphine milligram equivalents. Patient and prescription-related risk factors were evaluated utilizing logistic relative risk regression. We reserved a year of data, 222 people, to evaluate the performance of the derived model.
RESULTS
More than half the patients filled a second prescription for opioids within 30 days of TKA. Factors associated with a second prescription of opioid medication within 30 days of TKA included age (P < .01), current smoker (P = .01), and the total morphine milligram equivalents of the initial prescription (P < .01). Applied to the 222 people we reserved for validation, the model was 81% sensitive and 14% specific for a second prescription within 30 days, with a positive predictive value of 74%, and a negative predictive value of 20%.
CONCLUSION
People that are given more opioids tend to request more opioids, but our model had limited diagnostic performance characteristics indicating that we are not accounting for the key factors associated with a second opioid prescription. Future studies might address undiagnosed patient social and mental health opportunities, factors known to associate with pain intensity and satisfaction with pain alleviation.
LEVEL OF EVIDENCE
Diagnostic Level III.
Topics: Analgesics, Opioid; Arthroplasty, Replacement, Knee; Humans; Pain, Postoperative; Prescriptions; Retrospective Studies
PubMed: 32229150
DOI: 10.1016/j.arth.2020.03.001 -
The Clinical Journal of Pain Dec 2022People living with chronic pain may use wearable health technology (WHT) in conjunction with an expert-directed pain management program for up to 1 year. WHT use may be...
OBJECTIVES
People living with chronic pain may use wearable health technology (WHT) in conjunction with an expert-directed pain management program for up to 1 year. WHT use may be associated with improvements in key patient outcomes.
METHODS
A 12-month study of WHT use among people with chronic pain was conducted, consisting of iPhone and Apple Watch applications to measure movement, sleep, and self-reported pain. Clinical outcomes among 105 patients enrolled in a multidisciplinary pain program that included WHT use were compared with 146 patients in the same program but without WHT, and to 161 patients receiving medical pain management without WHT.
RESULTS
Participants used the WHT on average 143.0 (SD: 117.6) out of 365 days. Mixed-effects models revealed participants who used WHT had decreases in depression scores (-7.83, P <0.01) and prescribed morphine milligram equivalents (-21.55, P =0.04) over 1 year. Control groups also showed decreases in depression scores (-5.08, P =0.01; -5.68, P <0.01) and morphine milligram equivalents (-18.67, P =0.01; -10.99, ns). The estimated slope of change among the WHT was not statistically different than control groups.
DISCUSSION
Patients who used WHT as part of their pain management program demonstrated a willingness to do so for extended periods of time despite living with chronic pain and other comorbidities. Data trends suggest that WHT use may positively impact depression and prescribed medication. Additional research is warranted to investigate the potential of WHT to improve the negative consequences of chronic pain.
Topics: Humans; Chronic Pain; Pain Management; Biomedical Technology; Wearable Electronic Devices; Morphine Derivatives
PubMed: 36198095
DOI: 10.1097/AJP.0000000000001076 -
Journal of Blood Medicine 2021The prevalence of chewing and the use of ascorbic acid is increasing from time to time. Their subchronic effects on hematological indices are not well examined. The...
BACKGROUND
The prevalence of chewing and the use of ascorbic acid is increasing from time to time. Their subchronic effects on hematological indices are not well examined. The present study was aimed to investigate their subchronic effects on hematological indices in rats.
MATERIALS AND METHODS
A total of 36 adult (7-8 weeks) wild-type rats weighing between 213 and 229g were used in this study. They received extract (Ce) (100 milligrams/kilogram, 200 milligram/kilogram and 300 milligram/kilogram b.w), juice (2.5 mL/kg), ascorbic acid (AA 200 milligram/kilogram), and 2% tween 80 in distilled water (T80W- v/v) for twelve weeks. Hematological indices were measured with Sysmex KX-21. Data were analyzed by SPSS version 21.0 and Microsoft Excel.
RESULTS
Neutrocytes (p < 0.01), lymphocytes (p < 0.05), plateletcrit (p < 0.05), average size of platelets (p < 0.05), platelet size variability (p < 0.01), platelet-large cell ratio (p < 0.05) and neutrocytes/lymphocytes ratio (p < 0.001) were significantly greater, while hemoglobin concentration per red blood cell (p < 0.05) and hemoglobin concentration per volume of red blood cells were significantly reduced (p < 0.05) in rats received khat. The red cell distribution width (p < 0.05), platelet size variability (p < 0.05) and platelet-large cell ratio (p < 0.01) were significantly greater in rats received ascorbic acid.
CONCLUSION
Crude extract and juice changed some hematological indices and increased platelet activities. The platelet activity was also increased by ascorbic acid. The mechanisms for these changes need to be investigated.
PubMed: 34602828
DOI: 10.2147/JBM.S328703 -
Journal of Natural Products Jul 2021Monosaccharides play important roles in living organisms. They are present in essential glycoproteins, nucleic acids, and glycolipids as well as cell walls and bioactive...
Monosaccharides play important roles in living organisms. They are present in essential glycoproteins, nucleic acids, and glycolipids as well as cell walls and bioactive natural product glycosides and polysaccharides. Monosaccharides are optically active, and as a routine, scientists make sure that their absolute configurations are determined when new natural glycosides are isolated. Many determination methods for the absolute configuration of monosaccharides have been reported, and thus far, taking advantage of their optical rotation differences is the most used and efficient method to distinguish enantiomers. This method, however, is not very convenient, because it requires a milligram amount of each pure sample and the availability of a polarimeter. Identification methods dealing with comparison of the retention times of the d- and l-diastereomeric monosaccharide derivatives by GC, TLC values, HPLC, or UPLC have been also reported. Although effective, these methods still require sample preparation and a few milligrams of the test compounds. A new method with simple sample preparation to distinguish enantiomers of monosaccharides by analyzing the H NMR spectra of their diastereomeric derivatives has been developed. The monosaccharide components of a commercially available saponin-rich and monoglycosides have been successfully identified using this procedure.
Topics: Biological Products; Magnetic Resonance Spectroscopy; Molecular Structure; Monosaccharides; Panax; Stereoisomerism
PubMed: 34191514
DOI: 10.1021/acs.jnatprod.0c01120 -
Drug Metabolism and Disposition: the... Dec 2020Ertugliflozin is primarily cleared through UDP-glucurosyltransferase (UGT)-mediated metabolism (86%) with minor oxidative clearance (12%). In vitro phenotyping involved...
Ertugliflozin is primarily cleared through UDP-glucurosyltransferase (UGT)-mediated metabolism (86%) with minor oxidative clearance (12%). In vitro phenotyping involved enzyme kinetic characterization of UGTs or cytochrome P450 enzymes catalyzing formation of the major 3---glucuronide (M5c) and minor 2---glucuronide (M5a), monohydroxylated ertugliflozin (M1 and M3), and des-ethyl ertugliflozin (M2) metabolites in human liver microsomes (HLMs). Fractional clearance (f) from HLM intrinsic clearance (CL) indicated a major role for glucuronidation (f 0.96; CL 37 µl/min per milligram) versus oxidative metabolism (f 0.04; CL 1.64 µl/min per milligram). Substrate concentration at half-maximal velocity (K), maximal rate of metabolism (V), and CL for M5c and M5a formation were 10.8 µM, 375 pmol/min per milligram, and 34.7 µl/min per milligram and 41.7 µM, 94.9 pmol/min per milligram, and 2.28 µl/min per milligram, respectively. Inhibition of HLM CL with 10 µM digoxin or tranilast (UGT1A9) and 3 µM 16-phenyllongifolol (UGT2B7/UGT2B4) resulted in fraction metabolism (f) estimates of 0.81 and 0.19 for UGT1A9 and UGT2B7/UGT2B4, respectively. Relative activity factor scaling of recombinant enzyme kinetics provided comparable f for UGT1A9 (0.86) and UGT2B7 (0.14). K and V for M1, M2, and M3 formation ranged 73.0-93.0 µM and 24.3-116 pmol/min per milligram, respectively, and was inhibited by ketoconazole (M1, M2, and M3) and montelukast (M2). In summary, ertugliflozin metabolism in HLMs was primarily mediated by UGT1A9 (78%) with minor contributions from UGT2B7/UGT2B4 (18%), CYP3A4 (3.4%), CYP3A5 (0.4%), and CYP2C8 (0.16%). Considering higher ertugliflozin oxidative metabolism (f 0.12) obtained from human mass balance, human systemic clearance is expected to be mediated by UGT1A9 (70%), UGT2B7/UGT2B4 (16%), CYP3A4 (10%), CYP3A5 (1.2%), CYP2C8 (0.5%), and renal elimination (2%). SIGNIFICANCE STATEMENT: This manuscript describes the use of orthogonal approaches (i.e., enzyme kinetics, chemical inhibitors, and recombinant enzymes) to characterize the fraction of ertugliflozin metabolism through various UDP-glucuronosyltransferase (UGT) and cytochrome P450 (CYP) enzyme-mediated pathways. Phenotyping approaches routinely used to characterize CYP hepatic fractional metabolism (f) to estimate specific enzymes contributing to overall systemic clearance were similarly applied for UGT-mediated metabolism. Defining the in vitro metabolic disposition and f for ertugliflozin allows risk assessment when considering potential victim-based drug-drug interactions perpetrated by coadministered drugs.
Topics: Bridged Bicyclo Compounds, Heterocyclic; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Enzyme Assays; Glucuronosyltransferase; Hepatobiliary Elimination; Humans; Microsomes, Liver; Recombinant Proteins
PubMed: 33020067
DOI: 10.1124/dmd.120.000171 -
STAR Protocols Jun 2021Preparation of long single-stranded (ss)DNA in large quantities with high efficiency and purity remains a synthetic challenge. Here, we present a protocol for using...
Preparation of long single-stranded (ss)DNA in large quantities with high efficiency and purity remains a synthetic challenge. Here, we present a protocol for using DNA-hydrolyzing DNA enzymes (deoxyribozymes) for efficient biotechnological production of milligrams of ssDNA with a customizable sequence up to a few kilobases. Our protocol provides a convenient yet economical way to store the sequence information of target ssDNA on phages for selective mass production on demand. For complete details on the use and execution of this protocol, please refer to Jia et al. (2021).
Topics: Bacteriophages; Bioengineering; Biotechnology; DNA, Catalytic; DNA, Single-Stranded; Escherichia coli; Microscopy, Atomic Force
PubMed: 34027488
DOI: 10.1016/j.xpro.2021.100531 -
Surgery Aug 2021Optimal postoperative opioid stewardship combines adequate pain medication to control expected discomfort while avoiding abuse and community diversion of unused...
BACKGROUND
Optimal postoperative opioid stewardship combines adequate pain medication to control expected discomfort while avoiding abuse and community diversion of unused prescribed opioids. We hypothesized that an opioid buyback program would motivate patients to return unused opioids, and surgeons will use that data to calibrate prescribing.
METHODS
Prospective cohort study of postambulatory surgery pain management at a level II Veterans Affairs rural hospital (2017-2019). Eligible patients were offered $5/unused opioid pill ($50 limit) returned to our Veterans Affairs hospital for proper disposal. After 6 months, buyback data was shared with each surgical specialty.
RESULTS
Overall, 934 of 1,880 (49.7%) eligible ambulatory surgery patients were prescribed opioids and invited to participate in the opioid buyback. We had 281 patients (30%) return 3,165 unused opioid pills; this return rate remained constant over the study period. In 2017, 62.4% of patients were prescribed an opioid; after data was shared with providers, prescriptions for opioids were reduced to 50.7% and 38.3% of eligible patients in 2018 and 2019, respectively (P < .0001). The median morphine milligram equivalents prescribed also decreased from 108.8 morphine milligram equivalents in 2017 to 75.0 morphine milligram equivalents in 2018 and sustained at 75.0 morphine milligram equivalents in 2019 (P < .001). Surgical providers, surgeries performed, patient characteristics, and 30-day refill rates were similar throughout the study period.
CONCLUSION
A small financial incentive resulted in patients returning unused opioids after ambulatory surgery. Feedback to surgeons regarding opioids returned reduced the proportion of patients prescribed an opioid and the amount of opioid after ambulatory surgery without an increase in refills.
Topics: Adult; Aged; Aged, 80 and over; Ambulatory Surgical Procedures; Analgesics, Opioid; Female; Humans; Male; Middle Aged; Motivation; Pain Management; Pain, Postoperative; Practice Patterns, Physicians'; Prescription Drug Monitoring Programs; Prospective Studies
PubMed: 33676733
DOI: 10.1016/j.surg.2021.01.016