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The Western Journal of Emergency... Feb 2020Alteplase is the only Food and Drug Administration-approved intravenous (IV) thrombolytic medication for acute ischemic stroke. However, multiple recent studies... (Review)
Review
Alteplase is the only Food and Drug Administration-approved intravenous (IV) thrombolytic medication for acute ischemic stroke. However, multiple recent studies comparing tenecteplase and alteplase suggest that tenecteplase is at least as efficacious as alteplase with regards to neurologic improvement. When given at 0.25 milligrams per kilogram (mg/kg), tenecteplase may have less bleeding complications than alteplase as well. This narrative review evaluates the literature and addresses the practical issues with regards to the use of tenecteplase versus alteplase for acute ischemic stroke, and it recommends that physicians consider tenecteplase rather than alteplase for thrombolysis of acute ischemic stroke.
Topics: Acute Disease; Brain Ischemia; Fibrinolytic Agents; Humans; Infusions, Intravenous; Tenecteplase; Treatment Outcome
PubMed: 32191176
DOI: 10.5811/westjem.2020.1.45279 -
OTA International : the Open Access... Dec 2022Fragility fractures (low-energy, minimal-trauma fractures) are common in the aging population and can lead to decreased function, increased mortality, and long-lasting... (Review)
Review
Fragility fractures (low-energy, minimal-trauma fractures) are common in the aging population and can lead to decreased function, increased mortality, and long-lasting pain. Although opioids are helpful in reducing acute postoperative pain, they present risks that may lead to increased morbidity and mortality. This was a retrospective review of medical records of all Alaska Native and American Indian people older than 50 years, who received surgery for hip fracture repair between January 2018 and June 2019 (n = 128). We found that receipt of a peripheral nerve block (PNB) is a predictor for decreased length of hospital stay. However, receipt of PNB did not predict a reduction in postoperative morphine milligram equivalents opioid doses. Further study is required to determine whether one PNB method is superior to others based on individual-level characteristics.
PubMed: 36569104
DOI: 10.1097/OI9.0000000000000207 -
The Journal of Biological Chemistry Feb 2024Mammalian F-ATP synthase is central to mitochondrial bioenergetics and is present in the inner mitochondrial membrane in a dynamic oligomeric state of higher oligomers,...
Mammalian F-ATP synthase is central to mitochondrial bioenergetics and is present in the inner mitochondrial membrane in a dynamic oligomeric state of higher oligomers, tetramers, dimers, and monomers. In vitro investigations of mammalian F-ATP synthase are often limited by the ability to purify the oligomeric forms present in vivo at a quantity, stability, and purity that meets the demand of the planned experiment. We developed a purification approach for the isolation of bovine F-ATP synthase from heart muscle mitochondria that uses a combination of buffer conditions favoring inhibitor factor 1 binding and sucrose density gradient ultracentrifugation to yield stable complexes at high purity in the milligram range. By tuning the glyco-diosgenin to lauryl maltose neopentyl glycol ratio in a final gradient, fractions that are either enriched in tetrameric or monomeric F-ATP synthase can be obtained. It is expected that this large-scale column-free purification strategy broadens the spectrum of in vitro investigation on mammalian F-ATP synthase.
Topics: Animals; Cattle; Adenosine Triphosphate; Dimerization; Mitochondria, Heart; Mitochondrial Membranes; Mitochondrial Proton-Translocating ATPases; Centrifugation, Density Gradient
PubMed: 38159856
DOI: 10.1016/j.jbc.2023.105603 -
Mayo Clinic Proceedings. Innovations,... Feb 2023To describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain...
OBJECTIVE
To describe the pain intensity among hospitalized patients with calciphylaxis, elucidate the factors associated with pain improvement, and examine the link between pain improvement and clinical outcomes.
PATIENTS AND METHODS
Patients were identified from the Partners Research Patient Data Registry and the Partners Calciphylaxis Registry and Biorepository (Clinicaltrials.gov ID: NCT03032835). Those with calciphylaxis requiring hospitalization for at least 14 consecutive days during the study period from May 2016 through December 2021 were included. Pain intensity was assessed using patient-reported pain scores on numerical rating scales from 0 to 10. Associations between pain improvement and clinical outcomes, including lesion improvement, amputation, and mortality, were examined using univariate and multivariate regression models.
RESULTS
Our analysis included 111 patients (age, 58±14 years; men, 40%; on maintenance dialysis, 79%). No significant improvement of pain intensity was observed over the 14 days of hospitalization (mean difference, -0.71; =.08). However, among 49 (44.1%) patients who showed at least 1-point improvement in the pain score, there was an association with surgical debridement during hospitalization (odds ratio, 3.37; 95% CI, 1.17-9.67; =.02). Hyperbaric oxygen therapy was associated with pain improvement (odds ratio, 5.38; 95% CI, 1.14-25.50; =.03) in patients on maintenance dialysis. Pain improvement was associated with lower rates of subsequent amputation at 6 months of follow up (6% vs 13%; <.05) but did not predict lesion improvement or survival.
CONCLUSION
Pain control remains a challenge among hospitalized patients with calciphylaxis. Surgical debridement and hyperbaric oxygen therapy may improve pain intensity. Pain improvement predicted a lower risk of future amputation.
PubMed: 36712824
DOI: 10.1016/j.mayocpiqo.2022.12.006 -
STAR Protocols Mar 2021Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are multi-component, ATP-driven proton pumps, which play important roles in many physiological...
Vesicular- or vacuolar-type adenosine triphosphatases (V-ATPases) are multi-component, ATP-driven proton pumps, which play important roles in many physiological processes by acidifying intracellular vesicles, organelles, and the extracellular milieu. Long-standing challenges in purifying mammalian V-ATPases have limited the biochemical and structural study of mammalian V-ATPase. Here, we provide a protocol for purifying milligrams of human V-ATPase and detail procedures for the reconstruction of its structure by cryo-EM. Our method can be applied to any biochemical and biophysical study of human V-ATPase. For complete details on the use and execution of this protocol, please refer to Wang et al. (2020).
Topics: Cryoelectron Microscopy; HEK293 Cells; Humans; Protein Structure, Quaternary; Vacuolar Proton-Translocating ATPases
PubMed: 33665630
DOI: 10.1016/j.xpro.2021.100350 -
The International Journal on Drug Policy Dec 2021The Ottawa Inner City Health's Managed Opioid Program is the first, to our knowledge, to pair injectable opioid agonist hydromorphone treatment with assisted housing for...
BACKGROUND
The Ottawa Inner City Health's Managed Opioid Program is the first, to our knowledge, to pair injectable opioid agonist hydromorphone treatment with assisted housing for people experiencing homelessness with severe opioid use disorder (OUD) and injection drug use. We aimed to describe this program and evaluate retention, health, and social wellbeing outcomes.
METHODS
We retrospectively assessed the first cohort of clients enrolled in the Managed Opioid Program between August 2017-2018. The primary outcome was retention at 12 months. Secondary outcomes included injectable and oral opioid dose titration, non-prescribed opioid use, overdoses, connection with behavioural health services, and social well-being. Descriptive statistics were used to summarize baseline demographics and secondary outcomes. Actuarial survival analysis was used to assess retention among participants.
RESULTS
The study sample included 26 participants: median age was 36 years, 14 were female, 22 were White, eight had alcohol use disorders, 25 had stimulant use disorders, and all had a history of concurrent psychiatric illness. Retention at 12 months was 77% (95% CI 62-95). Throughout the first-year participants' opioid treatment doses increased. The median daily dose of injectable hydromorphone was 36 mg [17-54 mg] and 156 mg [108-188 mg] at enrollment and one year respectively. The median daily dose of oral opioid treatment was 120-milligram morphine equivalents [83-180 mg morphine equivalents] and 330-milligram morphine equivalents [285-428 mg morphine equivalents] at enrollment and one year respectively. Over half had no overdoses and there were no deaths among participants who remained enrolled. At one year, 45% stopped non-prescribed opioid use, 96% connected to behavioral health services, 73% reconnected with estranged families, and 31% started work or vocational programs.
CONCLUSION
Individuals with severe OUD engaged in injectable hydromorphone treatment and housing showed high retention in care and substantive improvements in patient-centered health and social well-being outcomes.
Topics: Adult; Alcoholism; Analgesics, Opioid; Canada; Female; Heroin; Housing; Humans; Hydromorphone; Opioid-Related Disorders; Retrospective Studies
PubMed: 34469781
DOI: 10.1016/j.drugpo.2021.103400 -
The American Journal of Managed Care Feb 2022To contribute to the literature of best-practice approaches to promote full mu agonist chronic opioid analgesic therapy (COAT) cessation in a population with chronic,...
OBJECTIVES
To contribute to the literature of best-practice approaches to promote full mu agonist chronic opioid analgesic therapy (COAT) cessation in a population with chronic, noncancer pain by describing initial and extended follow-up outcomes from a limited group program that utilized a standardized, multidisciplinary curriculum containing robust complementary care access in a private practice setting.
STUDY DESIGN
A retrospective review of data from electronic health records and the California Prescription Drug Monitoring Program for program participants between October 2017 and December 2019.
METHODS
Daily oral morphine milligram equivalent (MME) dose use upon entry, at program graduation, at 6 months post graduation, and at extended follow-up of 7 to 24 months post graduation were compared and reported for program participants.
RESULTS
A total of 109 program participants with incoming daily COAT use amounts as high as 600 MME (median, 60 MME; 25% quartile, 36.5 MME; 75% quartile, 90 MME; interquartile range, 53.5 MME) had a successful COAT cessation rate of 90% at program graduation, which was maintained at 6 months and extended follow-up at 95% and 97%, respectively.
CONCLUSIONS
This pilot study contributes to the literature by documenting a successful and potentially generalizable strategy to promote COAT cessation, and by providing unusually lengthy follow-up for postintervention COAT cessation monitoring.
Topics: Analgesics, Opioid; Chronic Pain; Drug Prescriptions; Humans; Pilot Projects; Practice Patterns, Physicians'; Prescription Drug Monitoring Programs; Retrospective Studies
PubMed: 35139290
DOI: 10.37765/ajmc.2022.88785 -
Tobacco Control May 2021Some jurisdictions have instituted limits on electronic cigarette (ECIG) liquid nicotine concentration, in an effort to control ECIG nicotine yield, and others are...
Some jurisdictions have instituted limits on electronic cigarette (ECIG) liquid nicotine concentration, in an effort to control ECIG nicotine yield, and others are considering following suit. Because ECIG nicotine yield is proportional to the product of liquid nicotine concentration (milligram per millilitre) and device power (watts) regulations that limit liquid nicotine concentration may drive users to adopt higher wattage devices to obtain a desired nicotine yield. In this study we investigated, under various hypothetical regulatory limits on ECIG liquid nicotine concentration, a scenario in which a user of a common ECIG device (SMOK TF-N2) seeks to obtain in 15 puffs the nicotine emissions equivalent to one combustible cigarette (ie, 1.8 mg). We measured total aerosol and carbonyl compound (CC) yields in 15 puffs as a function of power (15-80 W) while all else was held constant. The estimated nicotine concentration needed to achieve combustible cigarette-like nicotine yield at each power level was then computed based on the measured liquid consumption. We found that for a constant nicotine yield of 1.8 mg, reducing the liquid nicotine concentration resulted in greater amount of liquid aerosolised (p<0.01) and greater CC emissions (p<0.05). Thus, if users seek a given nicotine yield, regulatory limits on nicotine concentration may have the unintended consequence of increasing exposure to aerosol and respiratory toxicants. This outcome demonstrates that attempting to control ECIG nicotine yield by regulating one factor at a time may have unintended health effects and highlights the need to consider multiple factors and outcomes simultaneously when designing regulations.
Topics: Aerosols; Electronic Nicotine Delivery Systems; Hazardous Substances; Humans; Nicotine
PubMed: 32522818
DOI: 10.1136/tobaccocontrol-2019-055523 -
International Journal of Environmental... Dec 2022Among individuals with normal glucose tolerance (NGT), subjects with high levels of plasma glucose (≥155 mg/dL) at sixty minutes during an oral glucose tolerance test...
BACKGROUND AND OBJECTIVES
Among individuals with normal glucose tolerance (NGT), subjects with high levels of plasma glucose (≥155 mg/dL) at sixty minutes during an oral glucose tolerance test (1h-OGTT) are at an increased risk of developing type 2 diabetes. We investigated the association between the triglycerides and glucose (TyG) index, a novel marker of insulin resistance, with 1h-OGTT glucose plasma concentrations.
MATERIAL AND METHODS
1474 non-diabetic Caucasian subjects underwent a 75 g OGTT and were divided into two groups according to the cutoff 1h-OGTT plasma glucose < 155 mg/dL (NGT-1h-low) and ≥ 155 mg/dL (NGT-1h-high). The TyG index was calculated as ln [fasting triglycerides (milligrams per deciliter) × fasting blood glucose (milligrams per deciliter)/2]. Multivariable linear and logistic regression analyses were used to establish the contribution of the TyG index to the variability of 1h-OGTT glucose, and how the former affected the risk of being NGT-1h-high.
RESULTS
1004 individuals were NGT-1h-low and 470 were NGT-1h-high. The TyG index was higher for NGT-1h-high ( = 0.001) individuals, and it was an independent factor influencing 1h-OGTT glycemia (β = 0.191, < 0.001) after correcting for age, sex, and BMI. The TyG index was the strongest marker associated with the risk of being NGT-1h-high (OR = 1.703, CI 95% 1.34-2.17, < 0.001) when compared with FPG (OR = 1.054, CI 95% 1.04-1.07, < 0.001) and the HOMA-IR (OR = 1.156, CI 95% 1.08-1.23, < 0.001).
CONCLUSIONS
Our study demonstrated that the TyG index, an efficient and cost-effective marker of insulin resistance, is associated with the variability of early post-challenge glucose levels and is an independent marker of being NGT-1h-high.
Topics: Humans; Glucose Tolerance Test; Glucose; Insulin Resistance; Blood Glucose; Diabetes Mellitus, Type 2; Triglycerides
PubMed: 36613109
DOI: 10.3390/ijerph20010787 -
JAMA Network Open May 2023Repeated ketamine administration is common in treatment-refractory chronic pain, but ketamine analgesic and antidepressant effects are poorly understood in patients with...
IMPORTANCE
Repeated ketamine administration is common in treatment-refractory chronic pain, but ketamine analgesic and antidepressant effects are poorly understood in patients with chronic pain with depression symptoms.
OBJECTIVE
To determine clinical pain trajectories with repeated ketamine administrations, exploring whether ketamine dose and/or pretreatment depressive and/or anxiety symptoms may mediate pain relief.
DESIGN, SETTING, AND PARTICIPANTS
This nationwide, multicenter, prospective cohort study included patients in France with treatment-refractory chronic pain who received repeated ketamine administration, over 1 year, according to ketamine use in their pain clinic. Data were collected from July 7, 2016, through September 21, 2017. Linear mixed models for repeated data, trajectory analysis, and mediation analysis were performed from November 15 to December 31, 2022.
INTERVENTIONS
Ketamine administration in cumulative dose (milligrams) over 1 year.
MAIN OUTCOMES AND MEASURES
Primary outcome was mean pain intensity (0-10 on the Numerical Pain Rating Scale [NPRS]), assessed every month for 1 year by telephone, after inclusion in the hospital. Depression and anxiety (Hospital Anxiety and Depression Scale [HADS]), quality of life (12-item Short Form Health Survey [SF-12]), cumulative ketamine dose, adverse effects, and concomitant treatments were secondary outcomes.
RESULTS
A total of 329 patients (mean [SD] age, 51.4 [11.0] years; 249 women [75.7%] and 80 men [24.3%]) were enrolled. Repeated ketamine administration was associated with a decrease of NPRS (effect size = -0.52 [95% CI, -0.62 to -0.41]; P < .001) and an increase of SF-12 mental health (39.7 [10.9] to 42.2 [11.1]; P < .001) and physical health (28.5 [7.9] to 29.5 [9.2]; P = .02) dimension scores over 1 year. Adverse effects were in the normal range. There was a significant difference between patients without and with depressive symptoms in pain diminution (regression coefficient, -0.04 [95% CI, -0.06 to -0.01]; omnibus P = .002 for interaction of time × baseline depression [HADS score ≤7 or >7]). The mediation model showed that ketamine dose was not associated with pain diminution (r = 0.01; P = .61) and not correlated with depression (r = -0.06; P = .32), and that depression was associated with pain diminution (regression coefficient, 0.03 [95% CI, 0.01-0.04]; P < .001), whereas ketamine dose was not (regression coefficient, 0.00 [95% CI, -0.01 to 0.01]; P = .67). The proportion of reduction of pain mediated by baseline depression was 64.6%.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study on chronic refractory pain suggest that depression (and not ketamine dose or anxiety) was the mediator of the association of ketamine with pain diminution. This finding provides radically new insights on how ketamine reduces pain primarily by dampening depression. This reinforces the need for systematic holistic assessment of patients with chronic pain to diagnose severe depressive symptoms where ketamine would be a very valuable therapeutic option.
Topics: Male; Humans; Female; Middle Aged; Ketamine; Chronic Pain; Cohort Studies; Pain, Intractable; Quality of Life; Prospective Studies
PubMed: 37204789
DOI: 10.1001/jamanetworkopen.2023.14406