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Proceedings (Baylor University. Medical... 2023We hypothesized that patients who received an adductor canal block (ACB) in the operating room following unilateral total knee arthroplasty would have a lower oral...
BACKGROUND
We hypothesized that patients who received an adductor canal block (ACB) in the operating room following unilateral total knee arthroplasty would have a lower oral morphine milligram equivalent (MME) consumption during the postanesthesia care unit (PACU) phase 1 recovery period compared to patients who received an ACB in the PACU.
METHODS
This was a retrospective cohort study of patients who underwent robotic-assisted unilateral total knee arthroplasty under general anesthesia between March 1, 2020, and February 28, 2021, and received postoperative ACB either in the operating room or the PACU.
RESULTS
A total of 36 and 178 patients received postoperative ACB in the operating room and PACU, respectively, and had median and interquartile range MME consumption in the PACU of 22.5 (20-40) mg and 30.0 (20-40) mg ( = 0.76), respectively. Patients who had an ACB performed in the operating room and PACU had median and interquartile ranges of time spent in the PACU of 101 (75-178) minutes and 186 (125-272) minutes ( < 0.01), respectively.
CONCLUSION
Patients who received an ACB in the operating room did not have a lower OME consumption than patients who received an ACB in the PACU but did have a shorter PACU length of stay.
PubMed: 37829221
DOI: 10.1080/08998280.2023.2249372 -
Plastic and Reconstructive Surgery.... Apr 2023The purpose of this study was to evaluate opioid demand after open reduction and internal fixation of distal radius fractures in patients with and without a diagnosis of...
UNLABELLED
The purpose of this study was to evaluate opioid demand after open reduction and internal fixation of distal radius fractures in patients with and without a diagnosis of cannabis use.
METHODS
The PearlDiver database was queried for all patients who underwent open reduction and internal fixation of distal radius fractures between 2010 and 2020. Patients were categorized into two groups: (1) those with an active diagnosis of cannabis use (case) and (2) those without (control). The primary outcome measure was morphine milligram equivalents per prescription filled within 30 days after surgery. A logistic regression was used to determine potential risk factors associated with increased opioid filling patterns.
RESULTS
The rates of prescription refills before and after surgery were congruent in both the case and control populations and did not show significant differences ( > 0.05). The average morphine milligram equivalents of patients' first opioid prescription was significantly reduced in the case population compared with the control (352.26 versus 480.61 morphine milligram equivalents/prescription, = 0.005). A history of chronic opioid use was the strongest predictor of prolonged opioid prescription refills after surgery.
CONCLUSIONS
This study found a significant reduction in opioid volume in patients with a diagnosis of cannabis use who filled an opioid prescription after open reduction and internal fixation of distal radius fractures. Mental health diagnoses, specifically depression, showed an increased risk of multiple opioid prescription refills in patients without a diagnosis of cannabis use.
PubMed: 37020989
DOI: 10.1097/GOX.0000000000004901 -
The Journal of Biological Chemistry Apr 2024In the Alzheimer's disease (AD) brain, the microtubule-associated protein tau aggregates into paired helical filaments in which each protofilament has a C-shaped...
In the Alzheimer's disease (AD) brain, the microtubule-associated protein tau aggregates into paired helical filaments in which each protofilament has a C-shaped conformation. In vitro assembly of tau fibrils adopting this fold is highly valuable for both fundamental and applied studies of AD without requiring patient-brain extracted fibrils. To date, reported methods for forming AD-fold tau fibrils have been irreproducible and sensitive to subtle variations in fibrillization conditions. Here, we describe a route to reproducibly assemble tau fibrils adopting the AD fold on the multi-milligram scale. We investigated the fibrillization conditions of two constructs and found that a tau (297-407) construct that contains four AD phospho-mimetic glutamate mutations robustly formed the C-shaped conformation. 2D and 3D correlation solid-state NMR spectra show a single predominant set of chemical shifts, indicating a single molecular conformation. Negative-stain electron microscopy and cryo-EM data confirm that the protofilament formed by 4E-tau (297-407) adopts the C-shaped conformation, which associates into paired, triple, and quadruple helical filaments. In comparison, NMR spectra indicate that a previously reported construct, tau (297-391), forms a mixture of a four-layered dimer structure and the C-shaped structure, whose populations are sensitive to the environmental conditions. The determination of the NMR chemical shifts of the AD-fold tau opens the possibility for future studies of tau fibril conformations and ligand binding by NMR. The quantitative assembly of tau fibrils adopting the AD fold should facilitate the development of diagnostic and therapeutic compounds that target AD tau.
PubMed: 38679331
DOI: 10.1016/j.jbc.2024.107326 -
Annals of the Royal College of Surgeons... Jan 1997The phenomenon of ischaemic preconditioning protects the myocardium by limiting infarct size in animal models of ischaemia and reperfusion. Ischaemic preconditioning may... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The phenomenon of ischaemic preconditioning protects the myocardium by limiting infarct size in animal models of ischaemia and reperfusion. Ischaemic preconditioning may be induced by short periods of ischaemia and reperfusion. We investigated whether the human heart can be ischaemically preconditioned during coronary artery bypass grafting (CABG). Patients were enrolled into two separate studies. In the first study myocardial adenosine triphosphate (ATP) was used as the measured endpoint, assayed from myocardial biopsies taken at onset of cardiopulmonary bypass (CPB), at the end of the preconditioning stimulus, and at the end of a 10 min sustained ischaemic insult. In the second study the release of myocardial troponin T was used as the endpoint; taken at pre-CPB, and at 1, 6, 24, and 72 h after CPB. In both studies, patients were randomised into either the preconditioning group or the control group. Preconditioning was induced, after the onset of CPB, with two 3 min periods of crossclamping and an intervening 2 min of reperfusion, followed by 10 min sustained ischaemia. The control group only received 10 min of sustained ischaemia. Ischaemic preconditioning resulted in a slower rate of ATP (mumol/g dry weight) depletion in the preconditioned hearts at the end of the 10 min of sustained ischaemia (preconditioned: 11.5 +/- 0.8 vs control: 7.2 +/- 0.3; P < 0.005). Also, preconditioning resulted in a slower rate of troponin T release which was significantly different at 72 h after CPB in the preconditioned group (0.3 milligram) when compared with the control group (1.4 milligrams; P < 0.05). In addition, more patients in the preconditioned group had troponin T levels lower than 0.5 milligram at 72 h than in the control group (10 vs 3 patients). Both groups of patients received the same number of grafts, and underwent the same length of ischaemia during the procedure. We conclude that in patients undergoing CABG surgery, ischaemic preconditioning may reduce myocardial injury as shown by the favourable changes in myocardial ATP, and serum troponin T levels.
Topics: Adenosine Triphosphate; Aged; Biomarkers; Coronary Artery Bypass; Creatine Kinase; Humans; Ischemic Preconditioning, Myocardial; Lactic Acid; Middle Aged; Myocardium; Phosphocreatine; Troponin; Troponin T
PubMed: 9038496
DOI: No ID Found -
Clinical Journal of the American... Jun 2017The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes. (Observational Study)
Observational Study
BACKGROUND AND OBJECTIVES
The role of albuminuria as an indicator of progression has not been investigated in children with CKD in the absence of diabetes.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
Children were enrolled from 49 centers of the CKD in Children study between January of 2005 and March of 2014. Cross-sectional multivariable linear regression (=647) was used to examine the relationship between urine protein-to-creatinine (UP/C [milligrams per milligram]) and albumin-to-creatinine (ACR [milligrams per gram]) with eGFR (milliliters per minute per 1.73 m). Parametric time-to-event analysis (=751) was used to assess the association of UP/C, ACR, and urine nonalbumin-to-creatinine (Unon-alb/cr [milligrams per gram]) on the time to the composite endpoint of initiation of RRT or 50% decline in eGFR.
RESULTS
The median follow-up time was 3.4 years and 202 individuals experienced the event. Participants with a UP/C≥0.2 mg/mg and ACR≥30 mg/g had a mean eGFR that was 16 ml/min per 1.73 m lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. Individuals with ACR<30 mg/g, but a UP/C≥0.2 mg/mg, had a mean eGFR that was 9.3 ml/min per 1.73 m lower than those with a UP/C<0.2 mg/mg and ACR<30 mg/g. When categories of ACR and Unon-alb/cr were created on the basis of clinically meaningful cutoff values of UP/C with the same sample sizes for comparison, the relative times (RTs) to the composite end-point were almost identical when comparing the middle (RT=0.31 for UP/C [0.2-2.0 mg/mg], RT=0.38 for ACR [56-1333 mg/g], RT=0.31 for Unon-alb/cr [118-715 mg/g]) and the highest (RT=0.08 for UP/C [>2.0 mg/mg], RT=0.09 for ACR [>1333 mg/g], RT=0.07 for Unon-alb/cr [>715 mg/g]) levels to the lowest levels. A similar trend was seen when categories were created on the basis of clinically meaningful cutoff values of ACR (<30, 30-300, >300 mg/g).
CONCLUSIONS
In children with CKD without diabetes, the utility of an initial UP/C, ACR, and Unon-alb/cr for characterizing progression is similar.
Topics: Adolescent; Age Factors; Albuminuria; Biomarkers; Child; Creatinine; Cross-Sectional Studies; Disease Progression; Female; Glomerular Filtration Rate; Humans; Kaplan-Meier Estimate; Kidney; Linear Models; Male; Multivariate Analysis; North America; Prospective Studies; Renal Insufficiency, Chronic; Renal Replacement Therapy; Risk Factors; Time Factors
PubMed: 28546440
DOI: 10.2215/CJN.11971116 -
Journal of Dairy Science Apr 2018Several minerals are required for life to exist. In animals, 7 elements (Ca, P, Mg, Na, K, Cl, and S) are required to be present in the diet in fairly large amounts... (Review)
Review
Several minerals are required for life to exist. In animals, 7 elements (Ca, P, Mg, Na, K, Cl, and S) are required to be present in the diet in fairly large amounts (grams to tens of grams each day for the dairy cow) and are termed macrominerals. Several other elements are termed microminerals or trace minerals because they are required in much smaller amounts (milligrams to micrograms each day). In most cases the mineral in the diet must be absorbed across the gastrointestinal mucosa and enter the blood if it is to be of value to the animal. The bulk of this review discusses the paracellular and transcellular mechanisms used by the gastrointestinal tract to absorb each of the various minerals needed. Unfortunately, particularly in ruminants, interactions between minerals and other substances within the diet can occur within the digestive tract that impair mineral absorption. The attributes of organic or chelated minerals that might permit diet minerals to circumvent factors that inhibit absorption of more traditional inorganic forms of these minerals are discussed. Once absorbed, minerals are used in many ways. One focus of this review is the effect macrominerals have on the acid-base status of the animal. Manipulation of dietary cation and anion content is commonly used as a tool in the dry period and during lactation to improve performance. A section on how the strong ion theory can be used to understand these effects is included. Many microminerals play a role in the body as cofactors of enzymes involved in controlling free radicals within the body and are vital to antioxidant capabilities. Those same minerals, when consumed in excess, can become pro-oxidants in the body, generating destructive free radicals. Complex interactions between minerals can compromise the effectiveness of a diet in promoting health and productivity of the cow. The objective of this review is to provide insight into some of these mechanisms.
Topics: Acid-Base Equilibrium; Animals; Antioxidants; Cattle; Diet; Humans; Intestinal Mucosa; Minerals; Ruminants
PubMed: 29397180
DOI: 10.3168/jds.2017-13112 -
JAMA Internal Medicine Sep 2019Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk,...
IMPORTANCE
Prescription opioid misuse is a public health problem that leads to overdose. Although existing interventions focus on limiting prescribing to patients at high risk, individuals may still access prescription opioids dispensed to family members.
OBJECTIVE
To determine whether opioid prescriptions to family members were associated with overdose for individuals who themselves did not have an opioid prescription.
DESIGN, SETTING, AND PARTICIPANTS
We conducted a 1:4 matched case-control study using health care utilization data from 2004 through 2015 from a large US commercial insurance company. Eligible individuals were required to have at least 12 months of continuous enrollment and 1 or more family members in the database. Individuals who experienced overdose were identified by their first opioid overdose after the baseline period and matched to control participants by time in the database, calendar time, age, sex, and number of individuals in the family unit. Both groups were restricted to individuals with no prior opioid dispensing of their own. Data analysis was conducted from January 2018 to August 2018.
EXPOSURES
Any prior opioid dispensing to a family member, total morphine milligram equivalents dispensed to family members, and the type of opioid product dispensed.
MAIN OUTCOMES AND MEASURES
Individual odds of opioid overdose resulting in an emergency department visit or hospitalization were the primary end point. The primary analysis evaluated the odds of overdose among individuals whose family members had been dispensed an opioid. Sensitivity analyses examined the odds stratified by age and timing relative to the dispensing of opioids to family members.
RESULTS
A total of 2303 individuals who experienced opioid overdose and 9212 matched control individuals were identified. The mean (SD) age was 23.2 (18.1) years; 1158 affected individuals and 4632 control individuals (50.3%) were female. The mean (SD) time in the database before an overdose case was 3.2 (3.3) years. Prior opioid dispensing to family members was associated with individual overdose (odds ratio [OR], 2.89 [95% CI, 2.59-3.23]). There was a significant dose-response association between increasing amounts of opioids dispensed to family members and odds of overdose (>0-<50 morphine milligram equivalents per day: OR, 2.71 [95% CI, 2.42-3.03]; 50-<90 morphine milligram equivalents per day: OR, 7.80 [95% CI, 3.63-16.78]; ≥90 morphine milligram equivalents per day: OR, 15.08 [95% CI, 8.66-26.27]).
CONCLUSIONS AND RELEVANCE
In this analysis, opioid prescriptions to family members were associated with overdose among individuals who do not receive opioid prescriptions. Interventions may focus on expanding access to opioid antagonists, locking prescription opioids in the home, and providing greater patient education to limit fatal overdose among family members.
PubMed: 31233088
DOI: 10.1001/jamainternmed.2019.1064 -
Health Services Research Aug 2019To estimate the own-price elasticity of demand for naloxone, a prescription medication that can counter the effects of an opioid overdose, and predict the change in...
OBJECTIVE
To estimate the own-price elasticity of demand for naloxone, a prescription medication that can counter the effects of an opioid overdose, and predict the change in pharmacy sales following a conversion to over-the-counter status.
DATA SOURCES/STUDY SETTING
The primary data source was a nationwide prescription claims dataset for 2010-2017. The data cover 80 percent of US retail pharmacies and account for roughly 90 percent of prescriptions filled. Additional covariates were obtained from various secondary data sources.
STUDY DESIGN
We estimated a longitudinal, simultaneous equation model of naloxone supply and demand. Our primary variables of interest were the quantity of naloxone sold, measured as total milligrams sold at pharmacies, and the out-of-pocket price paid per milligram, both measured per ZIP Code and quarter-year.
DATA COLLECTION/EXTRACTION METHODS
Primary data came directly from payers and processors of prescription drug claims.
PRINCIPAL FINDINGS
We found that, on average, a 1 percent increase in the out-of-pocket price paid for naloxone would result in a 0.27 percent decrease in pharmacy sales. We predict that the total quantity of naloxone sold in pharmacies would increase 15 percent to 179 percent following conversion to over-the-counter status.
CONCLUSIONS
Naloxone is own-price inelastic, and conversion to over-the-counter status is likely to lead to a substantial increase in total pharmacy sales.
Topics: Adult; Commerce; Female; Humans; Male; Middle Aged; Models, Economic; Naloxone; Narcotic Antagonists; Nonprescription Drugs; Pharmacies; Socioeconomic Factors
PubMed: 30790269
DOI: 10.1111/1475-6773.13125 -
Cureus Sep 2023Ehlers-Danlos syndrome (EDS) is a rare disorder affecting the connective tissue, resulting in joint hypermobility, elastic skin, and often chronic pain, especially in...
Ehlers-Danlos syndrome (EDS) is a rare disorder affecting the connective tissue, resulting in joint hypermobility, elastic skin, and often chronic pain, especially in the hypermobility variant. Although opioids are commonly prescribed for pain, they can lead to opioid use disorder (OUD) and overdose. A 67-year-old female with Ehlers-Danlos syndrome hypermobility type (EDS-HT), osteoarthritis (OA), and anxiety received opioid-based pain management for a decade before changing her primary care physician. Her medications included oxycodone and morphine sulfate extended-release (ER) at different dosages. To lower overdose risk, her morphine milligram equivalents (MME) were tracked, and a step-by-step opioid tapering process was started. Diagnosing EDS is difficult due to symptom overlap with other connective tissue disorders. Chronic pain in EDS involves both nociceptive and neuropathic pain, necessitating a comprehensive pain management approach. The essential components of pain management include non-opioid medications, physical therapy, and psychological support. Opioids should be used cautiously in EDS patients because of connective tissue vulnerabilities and potential side effects. Personalized plans for opioid tapering may be appropriate for those on long-term opioid therapy. Managing EDS-related chronic pain requires a tailored, multidisciplinary approach. Early and accurate diagnosis and specialized healthcare providers familiar with EDS are crucial for effective pain management. Ongoing research and evidence-based pain management approaches are vital to address the unique needs of EDS patients, promoting better pain relief and overall well-being. Through meticulous evaluation and personalized treatment plans, healthcare professionals can better support EDS patients in managing chronic pain and reducing opioid dependence and misuse risks. A comprehensive approach, incorporating non-opioid medications, physical therapy, and psychological support, can offer effective pain relief and improve the quality of life for those living with EDS.
PubMed: 37745744
DOI: 10.7759/cureus.45713 -
PloS One 2024Liquid chromatography purification of multiple recombinant proteins, in parallel, could catalyze research and discovery if the processes are fast and approach the...
Liquid chromatography purification of multiple recombinant proteins, in parallel, could catalyze research and discovery if the processes are fast and approach the robustness of traditional, "one-protein-at-a-time" purification. Here, we report an automated, four channel chromatography platform that we have designed and validated for parallelized protein purification at milligram scales. The device can purify up to four proteins (each with its own single column), has inputs for up to eight buffers or solvents that can be directed to any of the four columns via a network of software-driven valves, and includes an automated fraction collector with ten positions for 1.5 or 5.0 mL collection tubes and four positions for 50 mL collection tubes for each column output. The control software can be accessed either via Python scripting, giving users full access to all steps of the purification process, or via a simple-to-navigate touch screen graphical user interface that does not require knowledge of the command line or any programming language. Using our instrument, we report milligram-scale, parallelized, single-column purification of a panel of mammalian cell expressed coronavirus (SARS-CoV-2, HCoV-229E, HCoV-OC43, HCoV-229E) trimeric Spike and monomeric Receptor Binding Domain (RBD) antigens, and monoclonal antibodies targeting SARS-CoV-2 Spike (S) and Influenza Hemagglutinin (HA). We include a detailed hardware build guide, and have made the controlling software open source, to allow others to build and customize their own protein purifier systems.
Topics: Animals; Coronavirus 229E, Human; SARS-CoV-2; Recombinant Proteins; Software; Programming Languages; Spike Glycoprotein, Coronavirus; Coronavirus OC43, Human; Mammals
PubMed: 38394072
DOI: 10.1371/journal.pone.0297879