bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Cyclooxygenase‐2 Inhibitor, Rofecoxib (VIOXX®), Did Not Alter the Antiplatelet Effects of Low‐Dose Aspirin in Healthy Volunteers
Authors: Greenberg Howard E. , Gottesdiener Keith , Huntington Martha , Wong Peggy , Larson Pat , Wildonger Lynn , Gillen Lisa , Dorval Ellen , Waldman Scott A.
Published: September 2022

The present study examined whether rofecoxib (VIOXX®), a new specific inhibitor of cyclooxygenase‐2 (COX‐2), would interfere with the desired antiplatelet effects of aspirin. Thus, the effects of rofecoxib on inhibition of ex vivo serumgenerated thromboxane B2 (TXB2) and platelet aggregation by low doses (81 mg) of aspirin were examined in healthy volunteers. This was a double‐blind, randomized, placebo‐controlled, parallel study of two treatment groups (n = 12 per group) in which subjects received 50 mg of rofecoxib or placebo for 10 days in a blinded fashion. Subjects also received 81 mg aspirin once on each of days 4 through 10 in an open‐label fashion. Blood for measurement of serum TXB2 production and platelet aggregation studies was collected on day 1 (prior to rofecoxib/placebo), on day 4 (prior to aspirin), and on day 10 (before and 4 hours following the seventh dose of aspirin). Platelet‐derived serum TXB2 (COX‐1 assay) was measured in blood clotted for 1 hour at 37°C. Platelet aggregation was independently induced employing 1 mM arachidonic acid and 1 μg/mL collagen as agonists. Rofecoxib administered alone had no significant effect on serum TXB2 production or platelet aggregation (day 4). TXB2 production was inhibited 98.4% by aspirin coadministered with either rofecoxib or placebo (day 10). Similarly, platelet aggregation induced by arachidonic acid was inhibited 93.7% and 93.5% by aspirin coadministered with either rofecoxib or placebo, respectively (day 10). The comparable values for inhibition of collagen‐induced platelet aggregation were 86.8% and 90.8%, respectively. No important clinical or laboratory adverse experiences were observed. In conclusion, rofecoxib alone (50 mg QD for 4 days) did not inhibit serum TXB2 production or platelet aggregation. In addition, rofecoxib (50 mg QD for 10 days) did not alter the antiplatelet effects of low‐dose aspirin (inhibition of platelet aggregation and TXB2 production). Rofecoxib was generally well tolerated when administered alone or in combination with low‐dose aspirin.
Rosiglitazone Does Not Affect the Steady‐State Pharmacokinetics of Digoxin
Authors: Di Cicco Robert A. , Miller Ann K. , Patterson Scott , Freed Martin I.
Published: September 2022

Rosiglitazone is a potent insulin‐sensitizing oral hypoglycemic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator‐activated receptor‐gamma (PPAR‐γ) nuclear receptor and improves glycemic control in patients with non‐insulin‐dependent diabetes mellitus. The potential for a drug‐drug interaction with oral digoxin was investigated. Subjects received both of the study regimens in a random sequence: digoxin 0.375 mg plus matching placebo for rosiglitazone orally each morning for 14 days or digoxin 0.375 mg plus 8 mg rosiglitazone orally each morning for 14 days. There was a 14‐day washout period between sessions. Blood and urine were collected over 24 hours beginning on the morning of day 14 for measurement of digoxin concentrations. An equivalence statistical approach was used, with rosiglitazone considered to have no effect on the pharmacokinetics of digoxin if the 90% confidence interval (CI) for the ratio of digoxin plus rosiglitazone relative to digoxin plus placebo was completely contained within the range (0.80, 1.25) for the primary end points, AUC(0–24), and C24. Digoxin AUC(0–24) and C24 values were similar for digoxin 0.375 mg plus matching placebo (18.5 ng•h/mL and 0.579 ng/mL, respectively) and digoxin 0.375 mg plus rosiglitazone (19.1 ng•h/mL and 0.594 ng/mL, respectively). Point estimates were 1.05 (90% CI: 1.01, 1.10) for AUC(0–24) and 1.04 (90% CI: 0.98, 1.11) for C24. Oral and renal clearance were also similar between regimens. Digoxin alone or in combination with rosiglitazone was safe and well tolerated. The most common adverse experience was headache. Coadministration of digoxin with rosiglitazone had no significant effect on the safety or steady‐state pharmacokinetics of digoxin.
A Review of the Pharmacologic and Pharmacokinetic Aspects of Rosuvastatin
Authors: White C. Michael
Published: September 2022

Rosuvastatin is a new HMG‐CoA reductase inhibitor with unique pharmacologic and pharmacokinetic properties. It has additional HMG‐CoA reductase enzyme‐binding interactions that cause tighter binding, has substantial active transport into hepatocytes, and has the lowest (LDL) for sterol synthesis in hepatocytes. Rosuvastatin 10 mg and 80 mg dosages have superior low‐density lipoprotein (LDL) cholesterol‐lowering efficacy as compared to atorvastatin 10 mg and 80 mg. Rosuvastatin 10 mg has also been shown to have superior LDL reductions to 20 mg of both simvastatin and pravastatin. This agent can raise high‐density lipoprotein (HDL) 8% to 12% and lower triglycerides by 10% to 35%. Rosuvastatin is a hydrophilic agent with poor penetration in extrahepatic tissue such as human umbilical vein endothelial cells and fibroblasts. It also has a low potential for cytochrome P450 drug interactions and can be dosed in the morning or night. In conclusion, rosuvastatin is an agent with molecular alterations that provide it with unique pharmacologic and pharmacokinetic effects. As such, it is a novel and unique HMG‐CoA reductase inhibitor for the treatment of hyperlipidemia.
Effect of Doxazosin on Arterial Elasticity: Functional versus Structural Changes
Authors: Bratteli Chris W , Glasser Stephen P.
Published: September 2022

Drugs and diseases have differential effects on functional and structural components of large‐conduit arteries and smaller vessels. The objective of this study was to demonstrate functional and structural effects of doxazosin (DOX) on large‐ vessel and small‐vessel arterial elasticity in hypertension (HTN). This was an open‐label, single‐blind, active‐therapy study. Patients with stage 1to 2 HTN were administered DOX 2 mg/day for 3 months and 4 mg/day for 1 month, if indicated, followed by 2‐week washout period. Arterial elasticity was measured noninvasively at baseline, at 3 months and 4 months of treatment, and 2 weeks following DOX withdrawal. Although the observed effects were not statistically significant, large‐vessel elasticity (C1) increased in a dose‐related manner and returned to baseline 2 weeks after drug withdrawal. There was a trend toward an increase in small‐vessel elasticity in a dose‐related manner. However, 2 weeks after drug withdrawal, C2 (distal elasticity) had not returned to baseline and was statistically significantly different from baseline (p = 0.032). It was concluded that large‐artery compliance increased in a dose‐related manner. Almost all benefit was lost within 2 weeks of discontinuation, suggesting the DOX effect was functional. Small‐artery compliance improved in a dose‐related manner but only partially returned to baseline after DOX withdrawal, suggesting changes in artery structure by DOX.
Lack of Correlation between the Steady‐State Plasma Concentrations of Haloperidol and Risperidone
Authors: Yasui‐Furukori Norio , Kondo Tsuyoshi , Mihara Kazuo , Suzuki Akihito , Inoue Yoshimasa , De Vries Ronald , Kaneko Sunao
Published: September 2022

Both haloperidol and risperidone have been widely used in the treatment of schizophrenia. Because of wider therapeutic spectrum of risperidone, switching from haloperidol to risperidone is recommended in patients who do not sufficiently respond to haloperidol. The present study investigated the correlation between the steady‐state plasma concentrations of haloperidol and risperidone together with the effects of CYP2D6 status on the steady‐state kinetics of both drugs. Subjects were 22 schizophrenic inpatients. Eleven patients first received risperidone 6 mg/day and then haloperidol 12 mg/day, while the remaining 11 patients received these two treatments in the opposite sequence. The steady‐state plasma concentrations of risperidone, 9‐hydroxyrisperidone, haloperidol, and reduced haloperidol were measured after the subjects had been on the treatment for at least 2 weeks, and CYP2D6 genotypes were identified in all subjects. Neither the correlation between the steady‐state plasma concentrations of haloperidol and those of risperidone (r = 0.061, ns) nor the active moiety (sum of concentration of risperidone and 9‐hydroxyrisperidone) of risperidone (r = 0.141, ns) was significant. The mean (± SD) plasma concentration of risperidone in patients with mutated allele(s)forCYP2D6 was significantly higher than those without mutated allele (1.5 ± 0.7 vs. 8.5 ± 11.0, p<0.05), while such a tendency for haloperidol was not observed. The present study suggests that the steady‐state plasma concentration of risperidone is not predicted from that of haloperidol in the same individual, probably because of the much greater involvement of CYP2D6 in the metabolism of risperidone than in that of haloperidol.
Safety, Tolerability, and Pharmacokinetics of Escalating High Doses of Ivermectin in Healthy Adult Subjects
Authors: Guzzo Cynthia A. , Furtek Christine I. , Porras Arturo G. , Chen Cong , Tipping Robert , Clineschmidt Coleen M. , Sciberras David G. , Hsieh John Y‐K. , Lasseter Kenneth C.
Published: September 2022

Safety and pharmacokinetics (PK) of the antiparasitic drug ivermectin, administered in higher and/or more frequent doses than currently approved for human use, were evaluated in a double‐blind, placebo‐controlled, dose escalation study. Subjects (n = 68) were assigned to one of four panels (3:1, ivermectin/placebo): 30 or 60 mg (three times a week) or 90 or 120 mg (single dose). The 30 mg panel (range: 347–594 μg/kg) also received a single dose with food after a 1‐week washout. Safety assessments addressed both known ivermectin CNS effects and general toxicity. The primary safety endpoint was mydriasis, accurately quantitated by pupillometry. Ivermectin was generally well tolerated, with no indication of associated CNS toxicity for doses up to 10 times the highest FDA‐approved dose of 200 μg/kg. All dose regimens had a mydriatic effect similar to placebo. Adverse experiences were similar between ivermectin and placebo and did not increase with dose. Following single doses of 30 to 120 mg, AUC and Cmax were generally dose proportional, with tmax ∼4 hours and t1/2 ∼18 hours. The geometric mean AUC of 30 mg ivermectin was 2.6 times higher when administered with food. Geometric mean AUC ratios (day 7/day 1) were 1.24 and 1.40 for the 30 and 60 mg doses, respectively, indicating that the accumulation of ivermectin given every fourth day is minimal. This study demonstrated that ivermectin is generally well tolerated at these higher doses and more frequent regimens.
Single‐Dose Pharmacokinetics and Safety of Pegylated Interferon‐α2b in Patients with Chronic Renal Dysfunction
Authors: Gupta Samir K. , Pittenger Amy L. , Swan Suzanne K. , Marbury Thomas C. , Tobillo Emlyn , Batra Vijay , Sack Marshall , Glue Paul , Jacobs Sheila , Affrime Melton
Published: September 2022

This study evaluates the pharmacokinetics and safety of pegylated interferon‐α2b (PEG‐Intron) following a singledose subcutaneous injection into subjects with normal renal function, subjects with chronic renal impairment, and patients on hemodialysis. In this open‐label, single‐dose, parallel‐group study, subjects were divided into five groups according to their degree of renal function: four groups as defined by measured creatinine clearance and a fifth hemodialysis‐dependent group. They received 1 μg/kg PEG‐Intron subcutaneously after a 10‐hour fast. Pharmacokinetic and safety assessments were performed up to 168 hours postdose. Hemodialysis patients had a second PEG‐Intron dose 12 hours prior to a hemodialysis session. PEG‐Intron pharmacokinetic parameters (AUCtf', Cmax' and t1/2) increased progressively as CLcr declined. All subjects reported at least one adverse event, which were typical of those reported after α‐interferon administration (e.g., flu‐like symptoms, headache). Single‐dose PEG‐Intron administration to volunteers with normal renal function and chronic renal impairment was safe and well tolerated. In patients with CLCR < 30 ml/min, AUC and Cmax values were increased 90% compared with controls, while half‐life was increased byup to 40% over controls. Based on the relationship between PEG‐Intron apparent clearance and CLCR' renal clearance accounts for less than half of its total clearance. Hemodialysis did not affect PEG‐Intron apparent clearance.
A Study in Normal Human Volunteers to Compare the Rate and Extent of Levothyroxine Absorption from Synthroid® and Levoxine®
Authors: Berg Jeffrey A. , Mayor Gilbert H.
Published: September 2022

Numerous branded and generic formulations of levothyroxine (LT4) sodium tablets are currently available. Results from previous studies attempting to examine the comparative bioavailability of these formulations are difficult to interpret because of subject heterogeneity, single time‐point blood sampling, varying degrees of hypothyroidism, and other factors. This study was devised to compare the rate and extent of absorption of LT4 from different LT4 sodium tablet formulations, in a simple model using a single‐dose two‐way single‐blind, randomized cross‐over design in 30 normal, healthy, nonpregnant, female subjects. This design controlled for many factors that limited previous LT4 bioavailability studies. Subjects were given a single 600 fig dose of LT4 as either Synthroid (Boots Pharmaceuticals, Inc., Lincolnshire, IL) tablets (formulation A) or Levoxine tablets (Daniels Pharmaceuticals, St. Petersburg, FL; formulation B). Measurements of baseline‐corrected total T4 serum concentrations determined at multiple time points demonstrated statistically significant differences between the two formulations at the 1.00, 3.00, 5.00, and 18.00 hour sampling times. Statistically significant differences for area under the curve (AUC) (0 to 48 hours) (formulation A, 159.9 ± 9.4 fig‐hour/dL; formulation B, 193.4 ± 10.1 μg‐hour/dL) and maximum peak plasma concentration (Cmax) (formulation A, 5.91 ± .34; formulation B, 7.12 ± .32) also were demonstrated. Furthermore, the ratio of the baseline‐corrected total T4 concentrations (B/A × 100) were 120.9% for AUC and 120.5% for Cmax. These data demonstrate that the administration of Synthroid and Levoxine result in a significantly different rate and extent of absorption of LT4, and therefore these two formulations cannot be considered bioequivalent. Interchange between these products can be expected to produce a different serum T4 concentration.
Bioavailability Studies of Drugs with Nonlinear Pharmacokinetics: I. Tracer Dose AUC Varies Directly with Serum Concentration
Authors: Browne T. R. , Szabo G. K. , Schumacher G. E. , Greenblatt D. J. , Evans J. E. , Evans B. A.
Published: September 2022

The authors show that for a drug cleared by one enzyme the area under the serum concentration‐time curve from time 0 to infinity (AUC0—INF) of a test dose can he expressed as AUC0—INF = TD × F × (Km + C)/Vmax where TD is test dose size, F is fraction absorbed, C is drug serum concentration at the time of the study, and Km and Vmax are the Michaelis constant and maximum velocity of the enzyme. This equation predicts the AUC0—INF produced by a given tracer dose of drug will vary directly with C in drugs with nonlinear pharmacokinetic properties (i.e., drugs whose value for C approaches or exceeds Km) if C is held constant by administration of tracer and maintenance doses of drug. The AUC0—INF produced by intravenous tracer doses of 150 mg of 13C15N2‐sodium phenytoin was determined in 15 subjects at 30 different values of C. AUC0—INF showed a high degree of direct linear correlation with C (AUC0—INF (ug · hr/mL) = 35.4 + 8.1 × C (ug/mL), r = 0.885, P <.0001). Consequences of this observation for relative bioavailability studies of drugs with nonlinear pharmacokinetic properties are discussed.
Open‐Label, Single‐Dose Pharmacokinetic Study of Modafinil Tablets: Influence of Age and Gender in Normal Subjects
Authors: Wong Y. Nancy , King S. Peter , Simcoe Donna , Gorman Steve , Laughton Watson , McCormick George C. , Grebow Peter
Published: September 2022

An open‐label, single‐center, single‐dose, parallel‐group study was performed in healthy young males and females as well as healthy elderly males to examine the influence of age and gender on the pharmacokinetics of modafinil following administration of a single 200 mg oral dose. Twelve subjects were enrolled in each of the following three groups: young males, young females, and elderly males. Each fasted (overnight) subject received 2 × 100 mg modafinil tablets. Blood and urine samples were collected at various times up to 72 hours postdose for the determination of plasma and urine levels of modafinil as well as the acid and sulfone metabolites. The plasma concentrations of the individual isomers, d‐ and l‐modafinil, were also determined. Pharmacokinetic parameters were determined by noncompartmental methods. Modafinil was well tolerated at a single oral dose of 200 mg. The most commonly reported adverse events were headache, fever, pharyngitis, and asthenia. There were no clinically meaningful differences with respect to the incidence rate of treatment‐emergent adverse events among the young female, young male, and old male groups. Modafinil was rapidly absorbed after oral dosing and slowly cleared (t1/2 ∼ 11–14 hr) from the body. Modafinil acid was the major urinary metabolite, which accounted for 35% to 60% of the dose. Results from this study indicated that there were age and gender effects on modafinil clearance processes. In this regard, the clearance rate of modafinil in males decreased with age while young females cleared modafinil at a faster rate than young males. Stereospecific pharmacokinetics of modafinil were also demonstrated. The d‐modafinil was eliminated three times faster than the l‐modafinil.
Sustained Hemodynamic Effects of the Selective Dopamine‐1 Agonist, Fenoldopam, during 48‐Hour Infusions in Hypertensive Patients: A Dose‐Tolerability Study
Authors: Taylor Addison A. , Mangoo‐Karim Roberto , Ballard Kevin D. , Luther Robert R. , Pool James L.
Published: September 2022

Eight patients with stage I‐II hypertension received a continuous IV infusion of the selective dopamine‐1 agonist, fenoldopam, for up to 48 hours at rates from 0.4 to 1.9 μg/kg/min. Hemodynamics and clinical symptoms during infusion were compared to the same parameters in the 24‐hour periods before and after infusion. Fenoldopam lowered blood pressure and increased heart rate. Greatest changes occurred during the first 12 hours of infusion and gradually returned toward preinfusion values throughout the remaining 36 hours in the six patients who completed 48 hours of infusion. Fenoldopam was discontinued within 2 hours of starting the infusion in two patients who received drug rates of 0.9 μg/kg/min and 1.9 μg/kg/min because of precipitous bradycardia. Clinical symptoms noted at fenoldopam doses higher than 0.8 μg/kg/min were headache, dizziness, diaphoresis, nausea and vomiting, and restlessness. In this pilot study, fenoldopam effectively reduced blood pressure in patients with stage I‐II hypertension for up to 48 hours, but fixed‐dose infusion rates above 0.8 μg/kg/min were associated with a high frequency of clinically significant and often intolerable adverse effects.
The Association of Opportunistic Infections with the Occurrence of Trimethoprim/Sulfamethoxazole Hypersensitivity in Patients Infected with Human Immunodeficiency Virus
Authors: Lehmann David F. , Liu Andrew , Newman Nancy , Blair Donald C.
Published: September 2022

Hypersensitivity from trimethoprim/sulfamethoxazole (TMP/SMX) has been linked to a reactive nitroso intermediate from sulfamethoxazole metabolism, which may be altered in patients with human immunodeficiency virus (HIV) infection. The authors determined the clinical factors that are associated with TMP/SMX hypersensitivity in patients with HIV. In a case control study, 54 controls currently tolerating TMP/SMX prophylaxis were randomly matched by date of hypersensitivity reaction in case patients to 28 patients with a history of a rash consistent with erythema multiforme from TMP/SMX. Demographic data, coadministered medications, laboratory data, and histories of opportunistic infections were extracted on all patients. A highly significant association was observed between the number of opportunistic infections and the occurrence of TMP/SMX hypersensitivity (p < 0.001), despite comparability of CD4 counts between case patients and controls (p > 0.1). A tendency for protection from TMP/SMX hypersensitivity in blacks was also observed (p = 0.066). These observations suggest that the mechanisms by which HIV produces cellular immune dysfunction and alters drug detoxification may be linked.
Learnings From Longitudinal Patient‐Reported and Clinical Outcomes in Palliative Head and Neck Cancer Care
Authors: Dorr Maarten C. , Sewnaik Aniel , Berzenji Diako , van Hof Kira S. , Grevelink Tim , Baatenburg de Jong Robert J. , Offerman Marinella P. J.
Published: September 2022

Objective

Patients with palliative head and neck cancer experience many symptoms in a short period of time. Longitudinal data on patient‐reported outcomes in this phase are lacking. The aim of this study is to use structurally obtained patient‐reported outcome data combined with clinical patient data and obtain insight in patient‐reported outcomes, survival, circumstances of death, and interventions and treatment during the palliative phase in order to improve the quality of end‐of‐life care and patient‐centered counseling.

Study Design

Longitudinal observational cohort study.

Setting

Tertiary cancer center.

Method

Quality of life was prospectively collected using the European Organization for Research and Treatment of Cancer QLQ‐C15‐PAL. Tumor‐ and patient‐specific data were retrospectively collected. Descriptive statistics, linear mixed models, and regression analyses were performed.

Results

A significant deterioration was found in global health status, physical functioning, fatigue, dyspnea, appetite loss, and constipation over time. However, emotional functioning improved. Median survival was 5.1 months, and only a low percentage of in‐hospital death was observed (7.8%). Higher global health status at intake was associated with prolonged survival.

Conclusion

Structural measurement of patient‐reported outcome together with clinical outcomes provides unique insight, which enables improvement of patient‐centered counseling and care.
Case Report of Wernicke’s Encephalopathy After Sleeve Gastrectomy
Authors: Hamilton Leslie A. , Darby Sarah H. , Hamilton Allan J. , Wilkerson Matthew H. , Morgan Kabel A.
Published: September 2022

Background: We report a case of a patient who was 3 months post–sleeve gastrectomy and presented with acute stroke symptoms ultimately due to Wernicke’s encephalopathy (WE) after bariatric surgery. A 20‐year‐old white female presented to an outside hospital 3 months after sleeve gastrectomy complaining of nausea and vomiting. She initially underwent a cholecystectomy and later became less responsive and required intubation. Magnetic resonance imaging changes, presumed to be an acute stroke, prompted her transfer to our facility. Intravenous (IV) thiamin was administered, and the patient’s symptoms improved over the course of her hospital stay. Results: Thiamin levels were markedly low, and the patient rapidly improved with the administration of IV thiamin. The patient was discharged to inpatient rehabilitation. Conclusion: Bariatric surgery is a less common cause of WE but can lead to acute WE due to malabsorption of thiamin. In patients undergoing bariatric surgery, clinicians should be vigilant about the potential for WE to occur. In addition, based on history, WE should be considered in the differential diagnosis for symptoms of acute ischemic stroke.
Immunoglobulin A and Protein Content of Low‐Fat Human Milk Prepared for the Treatment of Chylothorax
Authors: Drewniak Michelle , Waterhouse Chris C. M. , Lyon Andrew W. , Fenton Tanis R.
Published: September 2022

Background: Several case studies report successful recovery from chylothorax while infants were fed low‐fat human milk. The reported growth rates were inadequate despite milk supplementation with added medium‐chain triglycerides (MCTs). The objective was to determine the effect that various human milk fat separating methods, refrigerated centrifuge, room temperature centrifuge, and refrigeration have on the loss of immunoglobulin A (IgA) and protein in the preparation of low‐fat human milk. Methods: Protein and IgA were measured in 31 samples of reduced‐fat human milk. Reduced‐fat breastmilk samples were prepared by separating the fat using 3 methods (refrigerated centrifuge, room temperature centrifuge, and a refrigeration method), followed by lower fat milk extraction by syringe. Results: The refrigeration method decreased IgA concentration by 17% (P = .035) while centrifugation and fat removal from the human milk samples led to a 38% decline in IgA concentration in both the nonrefrigerated and refrigerated centrifuge samples (P < .0001 for both). Protein declined by 11% with refrigeration and fat removal (P < .0001) while centrifugation and fat removal decreased protein concentration by 31% (P < .0001) in both nonrefrigerated centrifuge and refrigerated centrifuge samples. Conclusions: Preparing low‐fat human milk for patients with chylothorax decreased the IgA and protein contents. As well as fat (in the form of MCTs), protein likely needs to be supplemented for infants fed low‐fat human milk to support adequate growth.
Amended Safety Assessment of Persulfates as Used in Cosmetics
Authors: Johnson Wilbur , Bergfeld Wilma F. , Belsito Donald V. , Hill Ronald A. , Klaassen Curtis D. , Liebler Daniel C. , Marks James G. , Shank Ronald C. , Slaga Thomas J. , Snyder Paul W. , Heldreth Bart
Published: September 2022

The Expert Panel for Cosmetic Ingredient Safety (Panel) reassessed the safety of 3 persulfate ingredients, which function as oxidizing agents in cosmetic products. The Panel reviewed relevant data relating to the safety of these ingredients and concluded that Ammonium, Potassium, and Sodium Persulfate are safe as used as oxidizing agents in hair colorants and hair lighteners designed for brief discontinuous use followed by thorough rinsing from the hair and skin. The Panel also concluded that the available data are insufficient for determining the safety of these persulfates in leave-on products and dentifrices.
A tale of two selection biases: The independent effects of relative age and biological maturity on player selection in the Football Association of Ireland's national talent pathway
Authors: Sweeney Liam , Cumming Sean P , MacNamara Áine , Horan Dan
Published: September 2022

This study investigated the associations between biological maturation status (classified using the Khamis–Roche method for the percentage of predicted adult height at the time of observation) and relative age (expressed as a decimal value relative to the difference between birth date and competition cut-off date) and the extent to which their relative selection biases existed across competitive age groups in an analysis of players within the Football Association of Ireland's (FAI) national talent pathway. The players assessed were either from the U13 FAI National Academy ( n = 125), the Ireland U15 national team ( n = 18), or the Ireland U16 national team ( n = 16). A moderate to very large selection bias in favour of early maturing players was observed across all age groups, increasing in magnitude with successive age groups ( p < 0.05). A total of 46–72% of players selected into the national talent pathway were early maturing; 0% of U15 and U16 players were late maturing. A relative age effect existed across all competitive cohorts ( p < 0.05), although not increasing with chronological age and smaller in magnitude than maturation biases. A small positive correlation between relative age and absolute maturity status at U13 was observed, and an inverse correlation between relative age and relative maturity status at U15 ( p < 0.01) was observed. There were no other significant correlations between relative or absolute maturity status and relative age. We encourage Football Associations to critically reflect upon their criteria for national talent squad selection; the current system diminishes the chances of selection for late maturing players.
A Broad Study to Develop Maternity Units Design Knowledge Combining Spatial Analysis and Mothers’ and Midwives’ Perception of the Birth Environment
Authors: Nicoletta Setola , Eletta Naldi , Cardinali Paola , Migliorini Laura
Published: September 2022

Objectives:

This article investigates how the physical birth environment is perceived by the users (women and midwives) in different settings, a midwife-led unit and an obstetric-led unit, placed in Italy.

Background:

In the field of birth architecture research, there is a gap in the description of the spatial and physical characteristics of birth environments that impact users’ health, specifically for what concerns the perception by women.

Methods:

The study focuses on multi-centered mixed methods design, employing both quantitative and qualitative research methods (questionnaire, spatial analysis) and covering different disciplines (architecture, environmental psychology, and midwifery).

Results:

The results revealed significant differences between the two settings and some associations between perceived and spatial data concerning: calm atmosphere, greater intimacy, spacious birth room, clarity of service points, clarity in finding midwives, sufficient space for labor, noise, privacy, and the birth room adaptability.

Conclusions:

The findings confirm the importance of the spatial layout and indicate documented knowledge as an input to consider when designing birth spaces in order to promote user well-being.
Quantitative evaluation of aortic valve regurgitation in 4D flow cardiac magnetic resonance: at which level should we measure?
Authors: Polacin Malgorzata , Geiger Julia , Burkhardt Barbara , Callaghan Fraser M. , Valsangiacomo Emanuela , Kellenberger Christian
Published: September 2022

Purpose

To find the best level to measure aortic flow for quantification of aortic regurgitation (AR) in 4D flow CMR.

Methods

In 27 congenital heart disease patients with AR (67% male, 31 ± 16 years) two blinded observers measured antegrade, retrograde, net aortic flow volumes and regurgitant fractions at 6 levels in 4D flow: (1) below the aortic valve (AV), (2) at the AV, (3) at the aortic sinus, (4) at the sinotubular junction, (5) at the level of the pulmonary arteries (PA) and (6) below the brachiocephalic trunk. 2D phase contrast (2DPC) sequences were acquired at the level of PA. All patients received prior transthoracic echocardiography (TTE) with AR severity grading according to a recommended multiparametric approach.

Results

After assigning 2DPC measurements into AR grading, agreement between TTE AR grading and 2DPC was good (κ = 0.88). In 4D flow, antegrade flow was similar between the six levels (p = 0.87). Net flow was higher at level 1–2 than at levels 3–6 (p < 0.05). Retrograde flow and regurgitant fraction at level 1–2 were lower compared to levels 3–6 (p < 0.05). Reproducibility (inter-reader agreement: ICC 0.993, 95% CI 0.986–0.99; intra-reader agreement: ICC 0.982, 95%CI 0.943–0.994) as well as measurement agreement between 4D flow and 2DPC (ICC 0.994; 95%CI 0.989 – 0.998) was best at the level of PA.

Conclusion

For estimating severity of AR in 4D flow, best reproducibility along with best agreement with 2DPC measurements can be expected at the level of PA. Measurements at AV or below AV might underestimate AR.
Application of a multimedia-supported manikin system for preclinical dental training
Authors: Yang Yi , Cheng Gu , Xing Xin , Li Zhi , Zhang Wei
Published: September 2022

Aim

In this study, we aimed to describe a multimedia-supported manikin system, compare the new manikin with the traditional manikin and evaluate its effectiveness in preclinical dentistry training.

Methods

A total of 150 students participated in this study. Amongst these students, 71 in the 2015-year group used traditional manikins (Group TM) for preclinical training courses (endodontics training courses and prosthodontics training courses), and 79 in the 2016-year group used manikins with a multimedia system (Group MM). The scores of the training courses between the two groups were compared. A questionnaire survey was used to collect opinions of the students in Group MM on their experience of using the multimedia-supported manikin system in the preclinical training.

Results

In the endodontics training courses, the scores of Group MM were higher than those of Group TM, but there was no significant difference (P = 0.379 > .05). However, the scores of prosthodontics training courses in Group MM were significantly higher than those in Group TM (P = 0.018 < .05). The questionnaire results indicated that the students in Group MM were satisfied with the device in usability, clarity, effectiveness and improvement in operation proficiency.

Conclusions

In the groups studied, for preclinical dental training, the multimedia-supported manikin system was a good alternative to traditional manikin in preclinical dentistry training.
Clinical ethics consultations: a scoping review of reported outcomes
Authors: Bell Jennifer A. H. , Salis Marina , Tong Eryn , Nekolaichuk Erica , Barned Claudia , Bianchi Andria , Buchman Daniel Z. , Rodrigues Kevin , Shanker Ruby R. , Heesters Ann M.
Published: September 2022

Background

Clinical ethics consultations (CEC) can be complex interventions, involving multiple methods, stakeholders, and competing ethical values. Despite longstanding calls for rigorous evaluation in the field, progress has been limited. The Medical Research Council (MRC) proposed guidelines for evaluating the effectiveness of complex interventions. The evaluation of CEC may benefit from application of the MRC framework to advance the transparency and methodological rigor of this field. A first step is to understand the outcomes measured in evaluations of CEC in healthcare settings.

Objective

The primary objective of this review was to identify and map the outcomes reported in primary studies of CEC. The secondary objective was to provide a comprehensive overview of CEC structures, processes, and roles to enhance understanding and to inform standardization.

Methods

We searched electronic databases to identify primary studies of CEC involving patients, substitute decision-makers and/or family members, clinicians, healthcare staff and leaders. Outcomes were mapped across five conceptual domains as identified a priori based on our clinical ethics experience and preliminary literature searches and revised based on our emerging interpretation of the data. These domains included personal factors, process factors, clinical factors, quality, and resource factors.

Results

Forty-eight studies were included in the review. Studies were highly heterogeneous and varied considerably regarding format and process of ethical intervention, credentials of interventionist, population of study, outcomes reported, and measures employed. In addition, few studies used validated measurement tools. The top three outcome domains that studies reported on were quality (n = 31), process factors (n = 23), and clinical factors (n = 19).The majority of studies examined multiple outcome domains. All five outcome domains were multidimensional and included a variety of subthemes.

Conclusions

This scoping review represents the initial phase of mapping the outcomes reported in primary studies of CEC and identifying gaps in the evidence. The confirmed lack of standardization represents a hindrance to the provision of high quality intervention and CEC scientific progress. Insights gained can inform the development of a core outcome set to standardize outcome measures in CEC evaluation research and enable scientifically rigorous efficacy trials of CEC.
A glycogen storage disease type 1a patient with type 2 diabetes
Authors: Sun Yi , Qiang Wenhui , Wu Runze , Yin Tong , Yuan Jie , Yuan Jin , Gu Yunjuan
Published: September 2022

Background

Glycogen storage disease type 1a (GSD1a) is an inborn genetic disease caused by glucose-6-phosphatase-α (G6Pase-α) deficiency and is often observed to lead to endogenous glucose production disorders manifesting as hypoglycemia, hyperuricemia, hyperlipidemia, lactic acidemia, hepatomegaly, and nephromegaly. The development of GSD1a with diabetes is relatively rare, and the underlying pathogenesis remains unclear.

Case presentation

Here we describe a case of a 25-year-old Chinese female patient with GSD1a, who developed uncontrolled type 2 diabetes mellitus (T2DM) as a young adult. The patient was diagnosed with GSD1a disease at the age of 10 and was subsequently treated with an uncooked cornstarch diet. Recently, the patient was treated in our hospital for vomiting and electrolyte imbalance and was subsequently diagnosed with T2DM. Owing to the impaired secretory function of the patient’s pancreatic islets, liver dysfunction, hypothyroidism, severe hyperlipidemia, and huge hepatic adenoma, we adopted diet control, insulin therapy, and hepatic adenoma resection to alleviate this situation. The WES discovered compound heterozygous mutations at the exon 5 of G6PC gene at 17th chromosome in the patient, c.648G>T (p.L216 L, NM_000151.4, rs80356484) in her father and c.674T>C (p.L225 P, NM_000151.4, rs1555560128) in her mother. c.648G>T is a well-known splice-site mutation, which causes CTG changing to CTT at protein 216 and creates a new splicing site 91 bp downstream of the authentic splice site, though both codons encode leucine. c.674T>C is a known missense mutation that causes TGC to become CGC at protein 225, thereby changing from coding for leucine to coding for proline.

Conclusion

We report a rare case of GSD1a with T2DM. On the basis of the pathogenesis of GSD1a, we recommend attentiveness to possible development of fasting hypoglycemia caused by GSD and postprandial hyperglycemia from diabetes. As the disease is better identified and treated, and as patients with GSD live longer, this challenge may appear more frequently. Therefore, it is necessary to have a deeper and more comprehensive understanding of the pathophysiology of the disease and explore suitable treatment options.
“They don’t go by the law around here”: law enforcement interactions after the legalization of syringe services programs in North Carolina
Authors: Morrissey Brandon , Hughes Tamera , Ostrach Bayla , Wilson Loftin , Getty Reid , Combs Tonya L. , Bennett Jesse , Carroll Jennifer J.
Published: September 2022

Background

In 2016, the US state of North Carolina (NC) legalized syringe services programs (SSPs), providing limited immunity from misdemeanor syringe possession when law enforcement is presented documentation that syringes were obtained from an SSP. This study explores the law enforcement interactions experienced by SSP participants since the enactment of this law.

Methods

This study used a convergent, mixed-methods design consisting of structured surveys and semi-structured interviews with SSP participants in seven NC counties. Survey and interview data were collected simultaneously between January and November 2019. This survey was designed to capture demographics, characteristics of drug use, SSP services used, and past-year negative experiences with law enforcement (officer did not recognize SSP card, did not believe SSP card belonged to participant, confiscated SSP card, confiscated syringes, or arrested participant for possessing syringes). Semi-structured interviews explored lived experiences with and perspectives on the same topics covered in the survey.

Results

A total of 414 SSP participants completed the survey (45% male, 54% female, 1% transgender or non-binary; 65% White, 22% Black, 5% American Indian/Alaskan Native, 8% some other racial identity). 212 participants (51.2%) reported at least one past-year negative experience with law enforcement. Chi-square testing suggests that Black respondents were more likely to report having experienced law enforcement doubt their SSP card belonged to them. Interview data indicate that law enforcement practices vary greatly across counties, and that negative and/or coercive interactions reduce expectations among SSP participants that they will be afforded the protections granted by NC law.

Conclusion

Despite laws which protect SSP participants from charges, negative law enforcement responses to syringe possession are still widely reported. Evidence-based policy interventions to reduce fatal overdose are undermined by these experiences. Our findings suggest NC residents, and officers who enforce these laws, may benefit from clarification as to what is required of the documents which identify participants of registered SSPs where they may legally obtain syringes. Likewise, more thorough trainings on NC’s syringe law for law enforcement officers may be merited. Further research is needed to assess geographic differences in SSP participants’ law enforcement interactions across race and gender.
Measuring COVID-19 health literacy: validation of the COVID-19 HL questionnaire in Spain
Authors: Falcón María , Rodríguez-Blázquez Carmen , Fernández-Gutiérrez Martina , Romay-Barja María , Bas-Sarmiento Pilar , Forjaz Maria João
Published: September 2022

Background

The COVID-19 pandemic has highlighted the importance of health literacy to make informed preventive decisions. A specific COVID-19 health literacy questionnaire (CHL-Q) is included in the COVID-19 Snapshot Monitoring WHO initiative to conduct behavioral insights studies related to COVID-19. The objective was to assess the psychometric properties of a Spanish version of the COVID-19 Health Literacy Questionnaire (CHL-Q).

Methods

Data quality, acceptability, internal consistency, and construct and structural validity were analyzed. A Rasch analysis was also performed. This cross-sectional, observational study was conducted on the Spanish general population after the first wave of the pandemic and after the end of the general lockdown by an online survey agency. 1033 participants (inclusion criteria were being 18 years or older and living in Spain), was extracted from a panel of approximately 982,000 participants. The sampling was stratified matching the Spanish general population in terms of age, gender, and area of residence. The CHL-Q includes 9 items and assesses people's knowledge, motivation and competencies to access, understand, evaluate, and apply information about COVID-19 in order to make informed decisions.

Results

CHL-Q index presented a mean of 33.89 (SD = 9.4), and good fit to the Rasch model (χ2(32) = 34.672, p = 0.342, person separation index = 0.77), with ordered thresholds, unidimensionality, item local independence, and no item bias by sex, age or education level. The CHL-Q showed significant different scores by level of education, experience of infection, confusion related to COVID-19 information and adherence to preventive measures. We found a statistically significant correlation between the CHL-Q index and the total number of preventive measures adopted, COVID-19 knowledge, and information seeking behaviour. The Cronbach´s alpha was 0.87 and the item total corrected correlation, 0.49–0.68.

Conclusions

The Spanish version of CHL-Q is a short, adequate, and reliable instrument to measure COVID-19 related health literacy in the Spanish general population. Measuring the CHL in the population can be useful to evaluate whether public authorities, media and the medical and scientific community have been able to reach the population to offer the information in the terms they need it.
Relations between family cohesion and adolescent-parent’s neural synchrony in response to emotional stimulations
Authors: Deng Xinmei , Lin Mingping , Zhang Lin , Li Xiaoqing , Gao Qiufeng
Published: September 2022

Background

The interaction between parent and adolescent is more challenging than in other age periods. Family cohesion seriously impacts parent-adolescent emotional interactions. However, the underlying neural mechanism has not been fully examined. This study examined the differences in the neural synchrony in response to emotional film clips between high and low family cohesion adolescent-parent dyads by using the electroencephalograph (EEG) hyperscanning.

Results

Simultaneously electroencephalograph (EEG) was recorded while 15 low family cohesion parent-adolescent dyads (LFCs)and 14 high family cohesion parent-adolescent dyads (HFCs)received different emotional induction when viewing film clips. Interbrain phase-locking-value (PLV) in gamma band was used to calculate parent-adolescent dyads’ interbrain synchrony. Results showed that higher gamma interbrain synchrony was observed in the HFCs than the LFCs in the positive conditions. However, there was no significant difference between the HFCs and LFCs in other conditions. Also, the HFCs had significantly higher gamma interbrain synchrony in the positive conditions than in the negative conditions.

Conclusion

Interbrain synchrony may represent an underlying neural mechanism of the parent-adolescent emotional bonding, which is the core of family cohesion.
Alamandine alleviated heart failure and fibrosis in myocardial infarction mice
Authors: Zhao Kun , Xu Tianhua , Mao Yukang , Wu Xiaoguang , Hua Dongxu , Sheng Yanhui , Li Peng
Published: September 2022

Alamandine (Ala) is the newest identified peptide of the renin-angiotensin system and has protective effect on myocyte hypertrophy. However, it is still unclear whether Ala can alleviate heart failure (HF). The aim of this study was to explore the effects of Ala on HF and the related cardiac fibrosis, and to probe the mechanism. HF model was induced by myocardial infarction (MI) in mice. Four weeks after MI, Ala was administrated by intraperitoneal injection for two weeks. Ala injection significantly improved cardiac dysfunction of MI mice in vivo. The cardiac fibrosis and the related biomarkers were attenuated after Ala administration in HF mice in vivo. The increases of collagen I, alpha-smooth muscle actin and transforming growth factor-beta induced by oxygen–glucose deprivation (OGD) in neonatal rat cardiac fibroblasts (NRCFs) were inhibited by Ala treatment in vitro. The biomarkers of apoptosis were elevated in NRCFs induced by OGD, which were attenuated after treating with Ala in vitro. The enhancement of oxidative stress in the heart of MI mice or in the NRCFs treated with OGD was suppressed by treating with Ala in vivo and in vitro. These effects of Ala were reversed by tBHP, an exogenous inducer of oxidative stress in vitro. These results demonstrated that Ala could alleviate cardiac dysfunction and attenuate cardiac fibrosis via inhibition of oxidative stress.