Changes In Vital Signs Research Articles

Evaluation of the effect of dental anxiety on vital signs in the order of third molar extraction

BackgroundDental anxiety is a prevalent concern affecting patients undergoing various dental procedures, particularly surgical interventions. Understanding the impact of patients’ anxiety levels on their physiological responses during dental surgeries, such as third molar impaction surgery, is crucial for optimizing patient care and outcomes. Therefore, this study aimed to investigate the effect of patients’ anxiety levels on vital signs during third molar teeth impaction surgery.MethodsA cross-sectional study was conducted, including 45 randomly selected, healthy patients. Demographic information was recorded after obtaining consent from the patients prior to surgical intervention. Preoperative anxiety levels were determined using the Modified Dental Anxiety Scale (MDAS). Pupil measurements were taken from the patients before surgery, at 10 min after the surgery began, and at 10 min after the surgery ended. Systolic (SBP) and diastolic (DBP) blood pressure, pulse rate, temperature, and haemoglobin oxygen saturation (SpO2) values were recorded.ResultsThe MDAS test results were statistically significantly higher in women compared to men (p < 0.001). Positive correlations were observed between MDAS score and both preoperative pulse rate (r = 0.344, p = 0.021) and SpO2 level during the operation (r = 0.462, p = 0.001). However, no significant correlations were found between MDAS and DBP (p = 0.575), SBP (p = 0.176), fever (p = 0.238), or pupil diameter (p = 0.338).ConclusionsThird molar impaction surgery induces anxiety in adult patients 20 years and older. Vital sign monitoring provides information about the patient’s emotional state, both before and during the procedure. Since anxiety causes changes in vital signs during dental procedures, it is important to follow these findings to have an idea about the general condition of the patients.

Effectiveness of buccal administration of dexmedetomidine and ketamine combination in paediatric dental sedation: A randomized controlled clinical trial.

Pain and anxiety can be considerable obstacles while treating paediatric dental patients. Moderate sedation is needed to treat uncooperative patients. This study aimed to compare the effectiveness of buccal administration of dexmedetomidine-ketamine combination versus dexmedetomidine. Fifty-six uncooperative children were randomly assigned into two groups: Group I received buccal dexmedetomidine (2 μg/kg) and ketamine (2 mg/kg) (DEX-KET), whereas Group II received buccal dexmedetomidine (4 μg/kg) (DEX). The effects of drugs were evaluated based on changes in vital signs, onset and duration of sedation, sedation level, analgesia, ease of treatment and procedural adverse effects. There were no significant differences in vital signs or sedation onset between the two groups. DEX-KET group showed shorter recovery time than DEX group (p < .0001). There were no statistically significant differences between both groups regarding sedation level at optimum sedation and during operative procedure (p = .064, p = .069 respectively). The ease of treatment was significantly better in DEX-KET group than in DEX group (p = .048). Procedural side effects and analgesic effects of the sedative drugs were comparable between both groups. The combination of dexmedetomidine and ketamine delivered buccally provided a better method of delivering care to uncooperative children with more rapid recovery than dexmedetomidine.

A double-blind, placebo-controlled, randomized multiple dose phase 1b trial of a CDK4/6 inhibitor, TCK-276, in patients with active rheumatoid arthritis.

The purpose of this study was to evaluate the safety, tolerability, pharmacokinetics, and efficacy (as an exploratory endpoint) of TCK-276, a novel CDK4/6 inhibitor, after multiple oral doses for 7 days in patients with active RA. This multicentre, randomized, placebo-controlled, dose-ascending, double-blind, phase 1b, multiple-dose study included 32 patients with active RA in 4 cohorts of 8 patients (6 active and 2 matching placebo), each receiving an oral dose of TCK-276 or matching placebo for 7 days (once daily). The doses of TCK-276 were 10, 25, 75, and 175 mg/day. Safety and pharmacokinetic endpoints, and exploratory disease activity parameters for RA were assessed. There were no deaths, serious adverse events, notable clinically meaningful laboratory findings (including hematological changes), clinically meaningful vital sign changes, or clinically meaningful electrocardiogram or cardiac telemetry changes. TCK-276 was rapidly absorbed and the half-life time ranged approximately from 6 to 12 hours. No obvious accumulation was observed, and the increase in TCK-276 exposure was dose proportional. At day 7, DAS28-CRP responses (EULAR good or moderate responses) were observed in 40%, 80%, and 66.7% at 25, 75, and 175 mg/day TCK-276, respectively, versus 12.5% in placebo; ACR20 responses were 33.3%, 60%, and 50% respectively, versus none in placebo. TCK-276 (≤175 mg) was well tolerated with no clinically meaningful safety signals in patients with active RA. Together with the preliminary efficacy (≥25 mg/day), these data warrant further study of TCK-276 for the treatment of active RA. ClinicalTrails.gov, NCT05437419.

Psilocybin Therapy for Females With Anorexia Nervosa: A Phase 1, Open-Label Feasibility Study.

Anorexia nervosa (AN) is a deadly illness with no proven treatments to reverse core symptoms and no medications approved by the US Food and Drug Administration. Novel treatments are urgently needed to improve clinical outcomes. In this open-label feasibility study, 10 adult female participants (mean body mass index 19.7 kg m-2; s.d. 3.7) who met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for AN or pAN (partial remission) were recruited to a study conducted at an academic clinical research institute. Participants received a single 25-mg dose of synthetic psilocybin in conjunction with psychological support. The primary aim was to assess safety, tolerability and feasibility at post-treatment by incidences and occurrences of adverse events (AEs) and clinically significant changes in electrocardiogram (ECG), laboratory tests, vital signs and suicidality. No clinically significant changes were observed in ECG, vital signs or suicidality. Two participants developed asymptomatic hypoglycemia at post-treatment, which resolved within 24 h. No other clinically significant changes were observed in laboratory values. All AEs were mild and transient in nature. Participants' qualitative perceptions suggest that the treatment was acceptable for most participants. Results suggest that psilocybin therapy is safe, tolerable and acceptable for female AN, which is a promising finding given physiological dangers and problems with treatment engagement. ClinicalTrials.gov identifier NCT04661514. Appeared originally in Nat Med 2023; 29:1947-1953.

A randomized, double-blind, placebo-controlled study on immune improvement effects of ethanolic extract of Echinacea purpurea (L.) Moench in Korean adults.

Echinacea purpurea (L.) Moench (EP), a medicinal plant native to North America, is now cultivated in various regions including Europe. With increasing popularity of Echinacea in Korea recently, a human clinical trial was conducted to evaluate immune-enhancing efficacy and safety of EP 60% ethanolic extract (EPE) in Koreans. Eighty volunteers were recruited for this randomized, double-blind, placebo-controlled clinical trial. They were randomly divided into two groups and given either a daily dose of 200 mg of EPE or a placebo. All participants underwent testing for Natural Killer (NK) cell cytotoxic activity, serum cytokine levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, TNF-α), Wisconsin Upper Respiratory Symptom Survey-21 (WURSS-21), and Multidimensional Fatigue Scale (MFS) during this study to assess changes in outcomes. After 8 weeks of EPE consumption, a significant increase in NK cell cytotoxic activity compared to the placebo was observed. Additionally, serum cytokine levels of IL-2, IFN-γ, and TNF-α also significantly increased following EPE consumption. However, no significant changes were observed in WURSS-21 and MFS before and after EPE consumption. Throughout the 8-week study period, no adverse reactions were reported in relation to EPE consumption, and there were no clinically significant changes in diagnostic laboratory tests or vital signs in the EPE group. These results indicate that consumption of EPE could lead to immune improvement without any adverse effects. This clinical trial was the first to demonstrate beneficial effects of EPE consumption on immunity in Korean adults.

A Randomized, Placebo-controlled Study to Assess the Efficacy and Safety of Herbal Extract and Micronutrient Blend Supplementation in People with Prediabetes

Background and Objective: Prediabetes is a precursor stage to type 2 diabetes mellitus (T2DM), characterized by elevated blood glucose levels. This study aimed to evaluate the efficacy and safety of herbal extract and micronutrient blend supplementation in managing prediabetes. Materials and Methods: This multicentric, randomized, placebo-controlled study involved 319 subjects with prediabetes (159 in the test group and 160 in the placebo group). Considering the dropouts, a total of 303 patients were analyzed. The test group received herbal extract and a micronutrient blend, while the placebo group received a placebo for 90 days along with lifestyle modifications. Anthropometric parameters, glycemic markers (glycated hemoglobin [HbA1c], fasting and postprandial plasma glucose, and homeostatic model assessment for insulin resistance [HOMA-IR]), lipid profile, perceived stress, and health-related quality of life (HRQoL) were assessed. Results: Compared to the placebo group, the test group exhibited significant improvements in anthropometric parameters (weight, body mass index, and body fat percentage), lipid profile, glycemic control (reduced HbA1c by 6.9%, fasting plasma glucose by 15.4%, postprandial plasma glucose by 8.9%, and HOMA-IR by 19.7%), perceived stress reduction, and enhanced HRQoL (P &lt; 0.001). The intervention was well-tolerated, with no clinically significant changes in lipid profiles, hematological parameters, or vital signs. Conclusion: Herbal extract and micronutrient blend supplementation effectively improved glycemic control, anthropometric parameters, and overall well-being in people with prediabetes, potentially reducing the risk of progression to T2DM.

Music to relieve pain and anxiety in cardiac catheterization: A systematic review and meta-analysis

Objectiveto evaluate the effectiveness of using music to relieve pain, anxiety, and change in vital signs in adult and older adult patients undergoing cardiac catheterization.Methodsthis is a systematic review with meta-analysis carried out in October 2022, using 12 data sources, without time or language restrictions. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The “Risk-of-bias tool” was used to assess the risk of bias, the “R CORE Team program: A language and environment for statistical computing” was used to perform the meta-analysis, and the “Grading of Recommendations Assessment, Development and Evaluation” was used to assess the quality of evidence in the studies. Resultsa total of nine studies were included, totaling 1456 participants. The most used tools for measuring anxiety were the State-Trait Anxiety Inventory and Numerical Rating Scale. This was also used to measure pain, in addition to the Visual Analogue Scale. The use of instrumental, classical and relaxing music prevailed, applied using headphones during the painful procedure, at a frequency of 60 to 100bpm and sound intensity of 60–70 dB. There was statistical significance in the use of music in reducing pain, anxiety and systolic blood pressure. Conclusionmusic interventions are effective in relieving pain, reducing systolic pressure and anxiety, but indifferent in terms of heart rate, respiratory rate and diastolic pressure. They provide humanization of care, can reduce hospital costs and length of hospital stay.

Chimeric Antigen Receptor T-Cell Postinfusion Fever: Infection Profile, Clinical Parameters, and Biomarkers Trends to Assist Antibiotic Stewardship.

This study aimed to describe documented infections associated with postinfusion fever after CAR T-cell therapy and to evaluate daily changes in vital signs, laboratory results, and the National Early Warning Score (NEWS) in patients with and without confirmed bacterial infections following fever onset, with the objective of assisting in antibiotic stewardship. This was a retrospective, observational study including all consecutive adult patients who received CAR T-cell therapy. Documented infection in the first fever episode after infusion, and clinical and analytic trend comparison of patients with bacterial documented infections and those without documented infections, are described. Among 152 patients treated with CAR T-cell therapy, 87 (57.2%) had fever within 30 days of infusion, with a median time from infusion to fever of 3 (interquartile range, 2-5) days. Of these 87 patients, 82 (94.3%) received broad-spectrum antibiotics. Infection was documented in 9 (10.3%) patients and only 4 (4.6%) had bacterial infections. Clinical signs and biomarkers were similar in patients with bacterial documented infection and in those without documented infection at fever onset. Fever, tachycardia, and high C-reactive protein levels remained high during the first 3 days after CAR T-cell infusion, even when no infection was documented. Fever is a common symptom following CAR T-cell infusion and is largely treated with broad-spectrum antibiotics. However, confirmed bacterial documented infections after the first fever post-CAR T-cell infusion are very unusual. Because clinical parameters and biomarkers are not useful for identifying infectious fever, other methods should be assessed to ensure the proper use of antibiotics.

Preclinical and first-in-human safety studies on a novel magnetism-based haemofiltration method

Extracorporeal haemofiltration devices that selectively remove cytokines could represent an adjunctive treatment in inflammatory diseases. One such device is the “IL-6-Sieve”, wherein magnetic Anti-IL-6 Beads are introduced into an extracorporeal circuit via a Bead Adapter and then removed along with any surface-bound interleukin (IL)-6 by a Filter deployed in a Magnet, before the blood is returned to the patient. We report here on a series of animal studies, and a first-in-human study, on the safety of the IL-6-Sieve. Evaluations focused on the: (a) safety of Filter and Magnet placed in an extracorporeal circuit in sheep; (b) safety of Anti-IL-6 Beads—directly infused intravenously as worst case scenario of misuse; or injected into an extracorporeal circuit using the Bead Adapter, Filter, and Magnet as intended—in sheep; (c) biodistribution of Anti-IL-6 Beads intravenously infused in mice; and (d) safety of Filter and Magnet placed in an extracorporeal circuit in healthy volunteers. No serious adverse events or significant changes in vital signs or routine laboratory parameters occurred in any of the animals or humans. Although safety of the IL-6-Sieve requires further study, these initial evaluations represent a promising start for the translation of this new blood purification modality into clinical use.

Application of Photodynamic Therapy with 5-Aminolevulinic Acid to Extracorporeal Photopheresis in the Treatment of Cutaneous T-Cell Lymphoma: A First-in-Human Phase I/II Study.

Extracorporeal photopheresis (ECP) is a therapeutic modality used for T-cell-mediated disorders. This approach involves exposing isolated white blood cells to photoactivatable 8-methoxypsoralen (8-MOP) and UVA light, aiming to induce apoptosis in T-cells and thereby modulate immune responses. However, conventional 8-MOP-ECP lacks cell selectivity, killing both healthy and diseased cells, and has shown limited treatment efficacy. An alternative approach under investigation involves the use of 5-aminolevulinic acid (ALA) in conjunction with light, referred to as ALA-based photodynamic therapy. Our previous ex vivo studies suggest that ALA-ECP exhibits greater selectivity and efficiency in killing T-cells derived from patients with T-cell-mediated disorders compared to those treated with 8-MOP-ECP. We have conducted a clinical phase I-(II) study evaluating ALA-ECP safety and tolerability in cutaneous T-cell lymphoma (CTCL). Here, 20 ALA-ECP treatments were administered to one CTCL patient, revealing no significant changes in vital signs. Two adverse events were reported; both evaluated by the Internal Safety Review Committee as non-serious. In addition, five conceivable events with mainly mild symptoms took place. During the study period, a 53% reduction in skin involvement and a 50% reduction in pruritus was observed. In conclusion, the results indicate that ALA-ECP treatment is safe and well tolerated.

Using Clinical-based Discharge Criteria to Discharge Patients After Endoscopy Procedures Under Drug-induced Intravenous Sedation in the Outpatient Care Unit: An Observational Study

PurposeTo verify the feasibility of clinical-based discharge (CBD) criteria and to find out the reasons for the delayed discharge of outpatients after endoscopy procedures under drug-induced intravenous sedation. DesignA prospectively observational study conducted at a tertiary endoscopy center. MethodsMedical records were collected from outpatients admitted for endoscopy procedures under drug-induced intravenous sedation from June 1, 2021 to December 30, 2021. Patients were scheduled to discharge at least 30 minutes based on the time-based discharge (TBD) method. Postanesthetic discharge scoring system in the outpatient post-anesthesia care unit (PACU) recorded the time of patients discharged home on the CBD criteria. Postoperative complications were recorded in the PACU and within 24 hours after discharge. Multivariate analysis was applied to identify the factors relating to late discharges. Findings10,597 patients were safely and successfully discharged home, and we were informed of no serious emergency or accidental readmissions to the hospital. The mean CBD time (21.77 ± 11.35 minutes) was compared with the TBD time (30 minutes) and actual TBD discharge time (61.56 ± 4.93 minutes), which were statistically significant, without changes in the patient's vital signs (P < .01). Primarily, further univariate and multivariate analyses showed that abdominal pain and fatigue were key factors accountable for delay in PACU discharge (P < .05). ConclusionsThe study concluded that in patients undergoing ambulatory endoscopy procedures with drug-induced intravenous sedation, discharge times based on physiological scoring systems can efficiently and safely guide ambulatory patient discharge as compared to the traditional TBD method. Postoperative fatigue and pain were the main factors affecting patients discharge associated with a relatively long PACU length of stay.

Predictive approach for liberation from acute dialysis in ICU patients using interpretable machine learning

Renal recovery following dialysis-requiring acute kidney injury (AKI-D) is a vital clinical outcome in critical care, yet it remains an understudied area. This retrospective cohort study, conducted in a medical center in Taiwan from 2015 to 2020, enrolled patients with AKI-D during intensive care unit stays. We aimed to develop and temporally test models for predicting dialysis liberation before hospital discharge using machine learning algorithms and explore early predictors. The dataset comprised 90 routinely collected variables within the first three days of dialysis initiation. Out of 1,381 patients who received acute dialysis, 27.3% experienced renal recovery. The cohort was divided into the training group (N = 1135) and temporal testing group (N = 251). The models demonstrated good performance, with an area under the receiver operating characteristic curve of 0.85 (95% CI, 0.81–0.88) and an area under the precision-recall curve of 0.69 (95% CI, 0.62–0.76) for the XGBoost model. Key predictors included urine volume, Charlson comorbidity index, vital sign derivatives (trend of respiratory rate and SpO2), and lactate levels. We successfully developed early prediction models for renal recovery by integrating early changes in vital signs and inputs/outputs, which have the potential to aid clinical decision-making in the ICU.

Comparison of Safety and Diagnostic Efficacy of Iohexol 240 mgI/mL, Iopamidol 250 mgI/mL, and Iodixanol 270 mgI/mL in Cerebral Angiography: A Prospective, Multicenter Study.

This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease. Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal-Wallis tests to assess the image quality and safety profiles of the contrast agents. Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection. Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients.

Outpatient blinatumomab with digital monitoring in patients with measurable residual disease positive (MRD+) B-ALL in a phase 4 study.

6544 Background: Blinatumomab, a CD3/CD19-directed BiTE® (bispecific T-cell engager) molecule, is an effective therapy for patients (pts) with MRD+ B-ALL. Hospitalization is recommended for days (D) 1–3 of cycle (C) 1 and D1–2 of C2 for these pts receiving blinatumomab to monitor for serious adverse events (SAEs). This phase 4 study evaluated the safety and feasibility of outpatient (outpt) digital monitoring to replace hospitalization in pts with MRD+ B-ALL (NCT04506086). Methods: Enrolled adults with MRD+ B-ALL in complete remission received continuous intravenous (cIV) blinatumomab at 28 μg/day. Current Health Wearable Monitoring System (CHWMS) was worn by pts at home for D1–3 (C1) and D1–2 (C2), in the presence of a caregiver, and provided heart rate, respiratory rate, and oxygen saturation; a separate patch monitored temperature. Manual blood pressure measurements were taken every 3-6 hrs. Vital signs (VS) were streamed to a provider smartphone/laptop; changes outside a predetermined threshold generated audible alarms. The primary endpoint was incidence of grade (G) ≥3 cytokine release syndrome (CRS), neurotoxicity, or any adverse event (AE) requiring hospitalization during the monitoring period. Results: As of 12/15/2023, 9 pts (median age 43 [20-73] years) received outpt blinatumomab for (completed C1, n=7; C2, n=6). During outpt monitoring, dose interruption was reported in 5 of 9 pts (1 pt had 2 dose interruptions: AE, n=2; dose administration error, n=2; other, n=2). CRS was reported in 2 pts (SAE, n=1; G≥3, n=0; led to interruption, n=1) and neurologic events in 4 pts (SAE, n=0; G≥3, n=0; led to interruption, n=0). Two pts experienced AEs requiring hospitalization (CRS, n=1; fever, n=1). Most VS changes were physiological or from routine pt activity. Median (range) number of alarms triggered/pt was 79 (12-135); among 3 pts, 1.2%, 5.1% and 8.9% of alarms led to therapeutic intervention (Table). Conclusions: To date, outpt administration of cIV blinatumomab in pts with MRD+ B-ALL was feasible and safe with appropriate outpt digital monitoring. Study enrollment is ongoing. Clinical trial information: NCT04506086 . [Table: see text]

A phase 1/1b first-in-human (FIH) study of JZP898 as monotherapy and in combination with pembrolizumab in adult patients with advanced or metastatic solid tumors.

TPS3190 Background: JZP898 is a conditionally activated prodrug of interferon alpha (IFNα) that can preferentially deliver IFNα to the tumor microenvironment while potentially minimizing systemic IFNα therapy-associated toxicity. Antitumor activity of IFNα is well-established, but concerns regarding systemic toxicity restrict its use in clinical practice. JZP898, in combination with a checkpoint inhibitor such as pembrolizumab, may provide lasting and potent antitumor activity with minimal additive toxicity attributed to conventional or pegylated IFNα. This phase 1 FIH study will determine a maximum tolerated dose (MTD)/recommended dose (RD) and investigate safety, tolerability, pharmacokinetics (PK), immunogenicity, and preliminary antitumor activity of JZP898 monotherapy and JZP898 combined with pembrolizumab in adult patients with advanced or metastatic solid tumors. Methods: This phase 1, FIH, open-label, multicenter study (NCT06108050) is investigating JZP898 intravenous infusion in adult patients (≥18 years old) with histological or cytological diagnosis of advanced or metastatic solid tumors, European Cooperative Oncology Group performance status ≤1, and measurable disease per RECIST v1.1 criteria. The study consists of a dose finding phase (JZP898 as monotherapy and in combination with pembrolizumab; Part A) and a combination dose expansion phase (JZP898 in combination with pembrolizumab; Part B). In Part A (dose finding), the JZP898 MTD and/or monotherapy RD will be determined using Bayesian optimal interval (BOIN) design based on the incidence of dose-limiting toxicities (DLTs) and all available safety and PK data; the combination recommended phase 2 dose (RP2D) will be determined using BOIN criteria and all available safety, PK/PD, immunogenicity, and preliminary signal of antitumor activity data. Patients will be treated until disease progression, death, unacceptable toxicity, or withdrawal from the study. All patients will be followed for survival until 18 months after the last patient starts study intervention. Primary endpoints include: the incidence and nature of DLTs (Part A); investigator-assessed objective response rate (ORR) per RECIST v1.1 (Part B); the incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse events; changes in laboratory values or vital signs; and the incidence of dose modifications or discontinuations due to TEAEs. Secondary endpoints include: PK parameters; incidence of antidrug antibodies; investigator-assessed duration of response; progression-free survival; disease control rate; investigator-assessed ORR (Part A); and overall survival (Part B). The study is actively enrolling patients with a planned enrollment of up to 177 patients. Clinical trial information: NCT06108050 .

Bicarbonate and Serum Lab Markers as Predictors of Mortality in the Trauma Patient.

Severe trauma-induced blood loss can lead to metabolic acidosis, shock, and death. Identification of abnormalities in the bicarbonate and serum markers may be seen before frank changes in vital signs in the hemorrhaging trauma patient, allowing for earlier lifesaving interventions. In this study the author aimed to evaluate the usefulness of serum bicarbonate and other lab markers as predictors of mortality in trauma patients within 30 days after injury. This retrospective, propensity-matched cohort study used the TriNetX database, covering approximately 92 million patients from 55 healthcare organizations in the United States, including 3.8 million trauma patients in the last two decades. Trauma patients were included if they had lab measurements available the day of the event. The analysis focused on mortality within 30 days post-trauma in comparison to measured lab markers. Cohorts were formed based on ranges of bicarbonate, lactate, and base excess levels. Before propensity score matching, a total of 1,275,363 trauma patients with same-day bicarbonate, lactate, or base excess labs were identified. A significant difference in mortality was found across various serum bicarbonate lab ranges compared to the standard range of 21-27 milliequivalents per liter (mEq/L), post-propensity score matching. The relative risk of death was 6.806 for bicarbonate ≤5 mEq/L; 8.651 for 6-10; 6.746 for 11-15; 2.822 for 16-20; and 1.015 for bicarbonate ≥28. Serum lactate also displayed significant mortality outcomes when compared to a normal level of ≤2 millimoles per liter. Base excess showed similar significant correlation at different values compared to a normal base excess of -2 to 2 mEq/L. This study, approximately 100 times larger than prior studies, associated lower bicarbonate levels with increased mortality in the trauma patient. While lactate and base excess offer prognostic value, lower bicarbonate values have a higher relative risk of death. The greater predictive value of bicarbonate and accessibility during resuscitations suggests that it may be the superior prognostic marker in trauma.

Safety and Efficacy of AlphaWave® L-Theanine Supplementation for 28Days in Healthy Adults with Moderate Stress: A Randomized, Double-Blind, Placebo-Controlled Trial.

Prolonged periods of stress may lead to negative health consequences. AlphaWave® L-Theanine was safe and efficacious during an acute stress challenge. However, double-blind, placebo-controlled clinical trials investigating the longer term effects of L-theanine supplementation on stress are warranted. Thirty healthy adults (18-65years) with moderate stress were randomized to AlphaWave® L-Theanine (400mg L-theanine/day) or placebo (n = 15/group) for 28days. Stress was assessed by salivary cortisol, Perceived Stress Scale (PSS) and Depression, Anxiety and Stress Scale-21; sleep was assessed by the Healthy People Sleep Quality Index and actigraphy device; cognition was assessed by Computerized Mental Performance Assessment System; mood was assessed by Profile of Mood States. All outcomes were measured at baseline, Days 14 and 28. Safety included vital signs, clinical chemistry, haematology and adverse events (AEs). All AEs were resolved by the end of the study period or upon subsequent follow up, and out of range laboratory values and changes in vital signs were deemed not clinically relevant following AlphaWave® L-Theanine supplementation. Participants supplemented with AlphaWave® L-Theanine had decreases of 12.92% (p = 0.051) and 17.98% (p = 0.04) in PSS scores after 14 and 28days, respectively, while those on placebo had respective decreases of 9.74% (p = 0.061) and 17.88% (p = 0.009). There were no significant differences between groups for change in salivary cortisol. The AlphaWave® L-Theanine group demonstrated decreased time asleep after 28days and significantly reduced light sleep after 14 and 28days compared to placebo (p ≤ 0.040). The AlphaWave® L-Theanine group significantly improved by 21.79% and 21.33% in Stroop test correct reaction time after 14 and 28days, respectively, while those on placebo improved after 28days only (p = 0.005). AlphaWave® L-Theanine supplementation for 28days was safe and significantly decreased perceived stress significantly decreased perceived stress and light sleep, improved sleep quality and enhanced cognitive attention in the studied population. Larger, randomized controlled trials with longer duration of AlphaWave® L-Theanine supplementation are warranted to reduce inter-individual variability and the potential placebo effect. ClinicalTrials.gov identifier, NCT05808595.

Evaluation of 68Ga-PSMA-11 PET/CT: a Phase 1 clinical study in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer

BackgroundProstate-specific membrane antigen (PSMA)-targeted radiopharmaceuticals allow whole-body imaging to detect prostate cancer (PC). Positron emission tomography imaging using gallium-68 (68Ga)-PSMA-11 has been shown to have a favorable safety and tolerability profile and high diagnostic performance. The study evaluates the safety and pharmacokinetics of 68Ga-PSMA-11 in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer.MethodsThis single arm study enrolled Japanese patients with primary PC (n = 3), suspected recurrent PC following radical prostatectomy (n = 4), or suspected recurrent PC following radical radiotherapy (n = 3). All patients received a single intravenous dose of 68Ga-PSMA-11 2.0 MBq/kg (±10%) followed by PSMA PET imaging and safety and pharmacokinetic evaluations. Based on the blood concentrations of 68Ga-PSMA-11 and the radioactivity distribution rate in each organ/tissue, the absorbed doses in major organs/tissues and the whole-body effective dose were calculated by the Medical Internal Radiation Dose method.ResultsTen patients were enrolled. Mean age was 73.3 ± 4.8 years, and median prostate-specific antigen was 8.250 ng/mL. Five patients (50%) experienced a total of 6 adverse events, and no grade ≥ 2 adverse events or serious adverse events were reported. No clinically significant changes in vital signs, haematology parameters, or blood chemistry or ECG abnormalities were observed. The estimated whole body effective dose of 68Ga-PSMA-11 (mean ± standard deviation) was 2.524 × 10–2 ± 2.546 × 10–3 mSv/MBq. Time to maximum concentration (1.16 × 10–4 ± 1.3 × 10–5% ID/mL) in whole blood was 2.15 ± 0.33 min.Conclusions68Ga-PSMA-11 has a favourable safety and tolerability profile in Japanese patients with primary, recurrent, or suspected recurrent prostate cancer, which is comparable to previous observations in other populations.

Comparison of Nebulized Ketamine to Intravenous Subdissociative Dose Ketamine for Treating Acute Painful Conditions in the Emergency Department: A Prospective, Randomized, Double-Blind, Double-Dummy Controlled Trial

Study objectiveWe aimed to assess and compare the analgesic efficacy and adverse effects of intravenous (IV) sub-dissociative-dose ketamine (SDK) to nebulized ketamine in emergency department (ED) patients with acute painful conditions. MethodsWe conducted a prospective, randomized, double-blinded, double-dummy clinical trial in adult patients (ages 18 to 64) with a numerical rating scale (NRS) pain score of >5. We randomized subjects to receive either a single dose of 0.3 mg/kg of IV ketamine or 0.75 mg/kg of nebulized ketamine via a breath-actuated nebulizer. Primary outcome was the difference in pain scores on the NRS between groups at 30 minutes post-medication administration. The secondary outcomes included the need for rescue analgesia, occurrences of adverse events in each group, and the difference in pain scores at 15, 30, 60, 90, and 120 minutes. We calculated a 95% confidence interval (CI) for a mean difference at 30 minutes, with a minimum clinically important difference set at 1.3 points. ResultsWe enrolled 150 subjects (75 per group). Mean pain scores via NRS were 8.2 for both groups at baseline, which decreased to 3.6 and 3.8 respectively at 30 minutes, yielding a mean difference of 0.23 (95% CI -1.32 to 0.857). We observed no clinically concerning changes in vital signs. No serious adverse events occurred in any of the groups throughout the study period. ConclusionWe found no difference between the administration of IV and nebulized ketamine for the short-term treatment of moderate to severe acute pain in the ED with both treatments providing a clinically meaningful reduction in pain scores at 30 minutes.

Radiosynthesis automation, non-human primate biodistribution and dosimetry of K+ channel tracer [11C]3MeO4AP

Background4-Aminopyridine (4AP) is a medication for the symptomatic treatment of multiple sclerosis. Several 4AP-based PET tracers have been developed for imaging demyelination. In preclinical studies, [11C]3MeO4AP has shown promise due to its high brain permeability, high metabolic stability, high plasma availability, and high in vivo binding affinity. To prepare for the translation to human studies, we developed a cGMP-compatible automated radiosynthesis protocol and evaluated the whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP in non-human primates (NHPs).MethodsAutomated radiosynthesis was carried out using a GE TRACERlab FX-C Pro synthesis module. One male and one female adult rhesus macaques were used in the study. A high-resolution CT from cranial vertex to knee was acquired. PET data were collected using a dynamic acquisition protocol with four bed positions and 13 passes over a total scan time of ~ 150 min. Based on the CT and PET images, volumes of interest (VOIs) were manually drawn for selected organs. Non-decay corrected time-activity curves (TACs) were extracted for each VOI. Radiation dosimetry and effective dose were calculated from the integrated TACs using OLINDA software.ResultsFully automated radiosynthesis of [11C]3MeO4AP was achieved with 7.3 ± 1.2% (n = 4) of non-decay corrected radiochemical yield within 38 min of synthesis and purification time. [11C]3MeO4AP distributed quickly throughout the body and into the brain. The organs with highest dose were the kidneys. The average effective dose of [11C]3MeO4AP was 4.0 ± 0.6 μSv/MBq. No significant changes in vital signs were observed during the scan.ConclusionA cGMP-compatible automated radiosynthesis of [11C]3MeO4AP was developed. The whole-body biodistribution and radiation dosimetry of [11C]3MeO4AP was successfully evaluated in NHPs. [11C]3MeO4AP shows lower average effective dose than [18F]3F4AP and similar average effective dose as other carbon-11 tracers.