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Journal of the American Pharmacists... 2023We aimed to increase pharmacists' and regulatory agencies' awareness of emerging issues regarding current practices of semaglutide use in the community that has led to...
BACKGROUND
We aimed to increase pharmacists' and regulatory agencies' awareness of emerging issues regarding current practices of semaglutide use in the community that has led to increased reports of administration errors and adverse drug events to our regional poison control center.
CASE SUMMARY
We report 3 cases of adverse drug events after incorrect administration of semaglutide for weight loss obtained from compounding pharmacies and an aesthetic spa. Two patients self-administered 10-fold dosing errors. All patients experienced notable symptoms of nausea, vomiting, and abdominal pain with most symptoms lasting for days. Other symptoms of headache, anorexia, weakness, and fatigue were reported in one patient. One patient sought evaluation at a health care facility and responded well to an antiemetic and intravenous fluids. One patient who received their medication from a compounding pharmacy reported receiving a vial with syringes for self-administration; no pharmacist counseling was provided on proper drug administration. One patient reported dosing in milliliters and units rather than in milligrams.
PRACTICE IMPLICATIONS
These 3 semaglutide cases highlight the potential for patient harm given current practices. Vials of compounded semaglutide do not use safety features provided by prefilled manufactured pens and allow for large overdoses (e.g., 10-fold dosing errors). Use of syringes not intended for semaglutide contributes to the variability of dosing units (milliliters, units, milligrams), contributing to patient confusion. To address such issues, we encourage increased vigilance in labeling, dispensing, and counseling practices to ensure patients are confident in administering their medication regardless of the formulation. We additionally encourage boards of pharmacy and other regulatory agencies to promote proper use and dispensing of compounded semaglutide. Such vigilance and promotion could decrease the risk of more severe adverse drug events and avoidable hospital utilization that may arise from dosing errors.
Topics: Humans; Poison Control Centers; Medication Errors; Pharmaceutical Preparations; Drug-Related Side Effects and Adverse Reactions; Pharmacists
PubMed: 37392810
DOI: 10.1016/j.japh.2023.06.017 -
International Journal of Gynecological... Dec 2021Opioids are routinely prescribed after minimally invasive gynecologic oncology surgery, with minimal data to inform the ideal dose. The aim of this study was to evaluate...
OBJECTIVES
Opioids are routinely prescribed after minimally invasive gynecologic oncology surgery, with minimal data to inform the ideal dose. The aim of this study was to evaluate the impact of a restrictive opioid prescription protocol on the median morphine milligram equivalents prescribed and pain control in patients undergoing minimally invasive surgery.
METHODS
A restrictive opioid prescription protocol was implemented from January through December 2020 at a single tertiary cancer center in Ontario, Canada. Consecutive patients undergoing minimally invasive hysterectomy for suspected malignancy were included. Simultaneously, we implemented use of multimodal analgesia, patient and provider education, pre-printed standardized prescriptions, and tracking of opioid prescriptions. Total median morphine milligram equivalents prescribed were compared between pre- and post-intervention cohorts. Patients were surveyed regarding opioid use and pain control at 30 days post-surgery.
RESULTS
A total of 101 women in the post-intervention cohort were compared with 92 consecutive pre-intervention controls. Following protocol implementation, median morphine milligram equivalents prescribed decreased from 50 (range 9-100) to 25 (range 8-75) (p<0.001). In the post-intervention cohort, 75% (76/101) used 10 median morphine milligram equivalents or less and 55 patients (54%) used 0 median morphine milligram equivalent. There was no additional increase in opioid refill requests after implementation of our strategy. Overall, patients reported a median pain score of 3/10 at 30 days post-surgery; the highest pain scores and most of the pain occurred in the first week after surgery.
CONCLUSIONS
Implementation of a restrictive opioid prescription protocol led to a significant reduction in opioid use after minimally invasive gynecologic oncology surgery, with over 50% of patients requiring no opioids postoperatively.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Opioid; Female; Genital Neoplasms, Female; Humans; Hysterectomy; Middle Aged; Minimally Invasive Surgical Procedures; Ontario; Pain Management; Pain, Postoperative; Quality Improvement; Surveys and Questionnaires
PubMed: 34750198
DOI: 10.1136/ijgc-2021-002968 -
The Western Journal of Emergency... Nov 2023Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2...
INTRODUCTION
Euglycemic diabetic ketoacidosis (DKA) (glucose <250 milligrams per deciliter (mg/dL) has increased in recognition since introduction of sodium-glucose co-transporter 2 (SGLT2) inhibitors but remains challenging to diagnose and manage without the hyperglycemia that is otherwise central to diagnosing DKA, and with increased risk for hypoglycemia with insulin use. Our objective was to compare key resource utilization and safety outcomes between patients with euglycemic and hyperglycemic DKA from the same period.
METHODS
This is a retrospective review of adult emergency department patients in DKA at an academic medical center. Patients were included if they were >18 years old, met criteria for DKA on initial laboratories (pH ≤7.30, serum bicarbonate ≤18 millimoles per liter [mmol/L], anion gap ≥10), and were managed via a standardized DKA order set. Patients were divided into euglycemic (<250 milligrams per deciliter [mg/dL]) vs hyperglycemic (≥250 mg/dL) cohorts by presenting glucose. We extracted and analyzed patient demographics, resource utilization, and safety outcomes. Etiologies of euglycemia were obtained by manual chart review. For comparisons between groups we used independent-group -tests for continuous variables and chi-squared tests for binary variables, with alpha 0.05.
RESULTS
We identified 629 patients with DKA: 44 euglycemic and 585 hyperglycemic. Euglycemic patients had milder DKA on presentation (higher pH and bicarbonate, lower anion gap; < 0.05) and lower initial glucose (195 vs 561 mg/dL, < 0.001) and potassium (4.3 vs 5.3 mmol/L, < 0.001). Etiologies of euglycemia were insulin use prior to arrival (57%), poor oral intake with baseline insulin use (29%), and SGLT2 inhibitor use (14%). Mean time on insulin infusion was shorter for those with euglycemic DKA: 13.5 vs 19.4 hours, = 0.003. Mean times to first bicarbonate >18 mmol/L and first long-acting insulin were similar. Incidence of hypoglycemia (<70 mg/dL) while on insulin infusion was significantly higher for those with euglycemic DKA (18.2 vs 4.8%, = 0.02); incidence of hypokalemia (<3.3 mmol/L) was 27.3 vs 19.1% ( = 0.23).
CONCLUSION
Compared to hyperglycemic DKA patients managed in the same protocolized fashion, euglycemic DKA patients were on insulin infusions 5.9 hours less, yet experienced hypoglycemia over three times more frequently. Future work can investigate treatment strategies for euglycemic DKA to minimize adverse events, especially iatrogenic hypoglycemia.
Topics: Adult; Humans; Adolescent; Diabetic Ketoacidosis; Bicarbonates; Insulin; Hypoglycemia; Glucose; Diabetes Mellitus
PubMed: 38165186
DOI: 10.5811/westjem.60361 -
Journal of Clinical Pharmacology Nov 2022In 1979, the late Dr. Darrell R. Abernethy and colleagues began a series of clinical studies aimed at understanding the pertinent determinants of drug distribution,... (Review)
Review
In 1979, the late Dr. Darrell R. Abernethy and colleagues began a series of clinical studies aimed at understanding the pertinent determinants of drug distribution, elimination, and clearance in obesity, and how those variables are interconnected. The studies confirmed that volume of distribution (V ) and clearance are the principal independent biological variables, which conjointly determine elimination of half-life as a dependent variable. For drugs distributed by passive diffusion, their pharmacokinetic V - after correcting for plasma protein binding - was increased in obesity, depending in part on the physicochemical lipophilicity of the individual drugs, and the quantitative extent of obesity in overweight individuals. Across all studies, the ratio of mean clearance in obese divided by control groups had an overall median value of 1.21 (range, 0.75-3.11), indicating a small and variable effect of obesity on clearance, without clear directionality. Since drug clearance was not clearly related to lipophilicity or degree of obesity, the prolonged half-life of lipophilic drugs in patients with obesity was largely explained by the increased V . Dr. Abernethy further identified delayed attainment of steady state after initiation of multiple-dose treatment, and delayed washout after termination of dosage, as potential clinical consequences of the extended half-life in people with obesity. These consequences for specific drugs have been recently emphasized in contemporary studies of chronic dosage in subjects with obesity. Without data identifying an obesity-related change in clearance for a specific drug, maintenance doses (in milligrams) should be based on ideal weight rather than adjusted upward on the basis of total weight.
Topics: Half-Life; Humans; Kinetics; Metabolic Clearance Rate; Obesity
PubMed: 35661375
DOI: 10.1002/jcph.2093 -
Heart (British Cardiac Society) Dec 2022Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular... (Review)
Review
Lipoprotein(a) (Lp(a)) is a complex circulating lipoprotein, and increasing evidence has demonstrated its role as a risk factor for atherosclerotic cardiovascular disease (ASCVD) and as a possible therapeutic target. Lp(a) atherogenic effects are attributed to several potential mechanisms in addition to cholesterol accumulation in the arterial wall, including proinflammatory effects mainly mediated by oxidised phospholipids. Several studies have found a causal and independent relationship between Lp(a) levels and cardiovascular risk. Furthermore, several studies also suggest a causal association between Lp(a) levels and calcific aortic valve stenosis. Available lipid-lowering agents have at best moderate impact on Lp(a) levels. Among available therapies, antibody proprotein convertase subtilisin/kexin type 9 inhibitors are the most effective in reducing Lp(a). Potent Lp(a)-lowering treatments that target expression are under development. Lp(a) level measurement poses some challenges due to the absence of a definitive reference method and the reporting of Lp(a) values as molar (nanomoles per litre (nmol/L)) or mass concentrations (milligrams per decilitre (mg/dL)) by different assays. Currently, Lp(a) measurement is recommended to refine cardiovascular risk in specific clinical settings, that is, in individuals with a family history of premature ASCVD, in patients with ASCVD not explained by standard risk factors or in those with recurrent events despite optimal management of traditional risk factors. Patients with high Lp(a) levels should be managed with more intensive approaches to treat other modifiable cardiovascular risk factors. Overall, this review focuses on Lp(a) as an ASCVD risk factor and therapeutic target. Furthermore, it reports practical recommendations for Lp(a) measurement and interpretation and updated evidence on Lp(a)-lowering approaches.
Topics: Humans; Lipoprotein(a); Atherosclerosis; Risk Factors; Aortic Valve Stenosis; Hypolipidemic Agents; Cardiovascular Diseases
PubMed: 35288443
DOI: 10.1136/heartjnl-2021-320708 -
Frontiers in Nutrition 2021Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood...
Type 2 Diabetes Mellitus (T2DM) is characterized by chronically elevated blood glucose (hyperglycemia) and elevated blood insulin (hyperinsulinemia). When the blood glucose concentration is 100 milligrams/deciliter the bloodstream of an average adult contains about 5-10 grams of glucose. Carbohydrate-restricted diets have been used effectively to treat obesity and T2DM for over 100 years, and their effectiveness may simply be due to lowering the dietary contribution to glucose and insulin levels, which then leads to improvements in hyperglycemia and hyperinsulinemia. Treatments for T2DM that lead to improvements in glycemic control and reductions in blood insulin levels are sensible based on this pathophysiologic perspective. In this article, a pathophysiological argument for using carbohydrate restriction to treat T2DM will be made.
PubMed: 34447776
DOI: 10.3389/fnut.2021.707371 -
Scientific Reports Apr 2023The impact of household processes on fenugreek leaves and seeds has been analyzed for total phenolic (TP) and total flavonoid content (TF), and in-vitro biological...
The impact of household processes on fenugreek leaves and seeds has been analyzed for total phenolic (TP) and total flavonoid content (TF), and in-vitro biological activities such as antioxidant, antimicrobial, and anti-inflammatory properties. Processes included air-drying for leaves and germinating, soaking, and boiling for seeds. Air-dried fenugreek leaves (ADFL) had high TP (15.27 mg GAE g D.W.) and TF (7.71 mg QE g D.W.) (milligram quercetin equivalents per gram dry weight). The TP contents of unprocessed, germinated, soaked, and boiled seeds were 6.54, 5.60, 4.59, and 3.84 mg gallic acid equivalents per gram of dry weight (mg GAE g D.W.), respectively. The TF contents in unprocessed fenugreek seeds, germinated fenugreek seeds, soaked fenugreek seeds, and boiled fenugreek seeds (BFS) were 4.23, 2.11, 2.10, and 2.33 mg QE g D.W., respectively. Sixteen phenolic and nineteen flavonoid compounds has been identified using high-performance liquid chromatography. Antioxidant activity using 2,2-diphenyl-1-picrylhydrazil (DPPH), 2,2-azinobis (3-ethylbenothiazoline-6-sulfonic acid (ABTS), and ferric reducing antioxidant power (FRAP) assays indicated that ADFL had the highest activity. Antimicrobial activity has been evaluated against each of the eight pathogenic bacterial and fungal strains. ADFL showed the strongest activity with minimum inhibitory concentrations values ranging from 0.03 to 1.06 and 0.04 to 1.18 mg ml against bacterial and fungal strains, respectively. Anti-inflammatory activity was evaluated in-vitro against RAW 264.7 macrophage cells using the nitric oxide (NO) assay. Results revealed that ADFL had the highest cytotoxicity and anti-inflammatory activity according to the NO assay. Household processes significantly reduced the in-vitro biological properties of processed seeds.
Topics: Antioxidants; Trigonella; Plant Extracts; Seeds; Phytochemicals; Phenols; Anti-Inflammatory Agents; Flavonoids
PubMed: 37120447
DOI: 10.1038/s41598-023-31888-y -
Analytical Sciences : the International... Jan 2021The crystalline sponge (CS) method was developed as an X-ray crystallographic molecular structure analysis method that can be performed without the need for... (Review)
Review
The crystalline sponge (CS) method was developed as an X-ray crystallographic molecular structure analysis method that can be performed without the need for crystallization of the analyte. CS has strong molecular-recognition properties and a highly flexible framework. The amount of analyte can be reduced to a sub-milligram level. These features of the crystalline nano-space allow for determining the absolute structure of a trace analyte. In this review, we focus on the discovery of the CS method and its applications to biosynthetic products in combination with NMR spectroscopy. We also describe some examples of the CS method that are used mainly in combination with mass spectrometry (MS). Both approaches demonstrate the potential of microanalysis to determine the molecular structure of an unknown sample. Finally, we mention the use of a crystalline "nano-surface" rather than a crystalline nano-space in MS, which can detect small metabolites as well as post-translation biomolecules.
Topics: Crystallography, X-Ray; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
PubMed: 33132236
DOI: 10.2116/analsci.20SAR07 -
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 -
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