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1.
Ann Biomed Eng ; 2024 Oct 02.
Article in English | MEDLINE | ID: mdl-39356379

ABSTRACT

PURPOSE: The study purpose was to investigate the laboratory-based performance of three commercially available shell add-on products under varsity-level impact conditions. METHODS: Pendulum impact tests were conducted at multiple locations (front, front boss, rear, side) and speeds (3.1, 4.9, 6.4 m/s) using two helmet models. Tests were performed with a single add-on configuration for baseline comparisons and a double add-on configuration to simulate collisions with both players wearing shell add-ons. A linear mixed-effect model was used to evaluate peak linear acceleration (PLA), peak rotational acceleration (PRA), and concussion risk, which was calculated from a bivariate injury risk function, based on shell add-on and test configuration. RESULTS: All shell add-ons decreased peak head kinematics and injury risk compared to controls, with the Guardian NXT producing the largest reductions (PLA: 7.9%, PRA: 14.1%, Risk: 34.1%) compared to the SAFR Helmet Cover (PLA: 4.5%, PRA: 9.3%, Risk: 24.7%) and Guardian XT (PLA: 3.2%, PRA: 5.0%, Risk: 15.5%). The same trend was observed in the double add-on test configuration. However, the Guardian NXT (PLA: 17.1%; PRA: 11.5%; Risk: 62.8%) and SAFR Helmet Cover (PLA: 12.2%; PRA: 9.1%; Risk: 52.2%) produced larger reductions in peak head kinematics and injury risk than the Guardian XT (PLA: 5.7%, PRA: 2.2%, Risk: 21.8%). CONCLUSION: In laboratory-based assessments that simulated varsity-level impact conditions, the Guardian NXT was associated with larger reductions in PLA, PRA, and injury risk compared to the SAFR Helmet Cover and Guardian XT. Although shell add-ons can enhance head protection, helmet model selection should be prioritized.

2.
J Clin Med ; 13(17)2024 Aug 25.
Article in English | MEDLINE | ID: mdl-39274237

ABSTRACT

Background/Objectives: In this observational prospective cohort study, conducted at the Fertility Centre of the University Hospital, Duesseldorf Germany, the spontaneous reversal capacity and the effect of waiting time on an adverse vaginal microbiome profile in subfertile patients were investigated. Methods: Vaginal swabs of 76 patients were obtained before starting a fertility treatment using a commercially available test to perform a microbiome analysis. Patients with a favorable microbiome profile ("medium" or "high profile") according to the manufacturer's algorithm proceeded with the fertility treatment. Patients with an unfavorable microbiome profile ("low profile") postponed their fertility treatment and were sampled up to four times in each successive cycle or until a shift to a more favorable profile was detected. Results: Initially, 54/76 subjects had a high or medium profile and 23/76 had a low profile. Within 3 months, 75% of patients with an initial low profile shifted to a more favorable profile (7/23 dropouts). The presence of Lactobacillus crispatus in the initial sample was associated with a higher likelihood of a spontaneous shift to a more favorable profile. Conclusions: The vaginal microbiome is subject to strong fluctuations. Even an unfavorable microbiome profile can develop into a favorable microbiome profile within a few months without treatment.

3.
Cancer Immunol Immunother ; 73(11): 227, 2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39249118

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are rarely used to treat advanced pancreatic ductal adenocarcinoma (PDAC) due to marginal efficacy. PATIENTS AND METHODS: This study included 92 consecutive patients diagnosed with advanced or recurrent PDAC who received nivolumab-based treatment. Univariate and multivariate analyses were used to identify prognostic factors. A control group of 301 patients with PDAC who achieved disease control with palliative chemotherapy but without ICIs was selected for comparison using propensity score matching (PSM). RESULTS: The median overall survival (OS) since nivolumab treatment was 15.8 (95% confidence interval [CI], 12.5-19.0), 2.4 (95% CI 1.2-3.6), and 1.1 (95% CI 1.0-1.2) months in patients who received add-on nivolumab after achieving disease control with chemotherapy, in those who received concomitant nivolumab and chemotherapy without prerequisite confirmation of disease control, and in those who received nivolumab without concomitant chemotherapy, respectively (P < 0.001). After PSM, the median overall survival (OS) since initiation of the concomitant chemotherapy that achieved disease control was significantly longer (P = 0.026) in patients who received add-on nivolumab (19.8 months; 95% CI 14.5-25.1) than in those who received chemotherapy alone (13.8 months; 95% CI 10.8-16.9). The immune profiling of the tumors in resected patients revealed higher scores of CD8+ T cells to Tregs in patients with add-on nivolumab comparing to those who received chemotherapy alone. CONCLUSION: Adding-on nivolumab was associated with improved OS in patients with advanced PDAC who achieved disease control following chemotherapy.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Carcinoma, Pancreatic Ductal , Nivolumab , Pancreatic Neoplasms , Humans , Male , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/mortality , Carcinoma, Pancreatic Ductal/pathology , Nivolumab/therapeutic use , Nivolumab/administration & dosage , Female , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/mortality , Aged , Middle Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Prognosis , Immune Checkpoint Inhibitors/therapeutic use , Adult , Aged, 80 and over , Retrospective Studies
4.
Expert Opin Pharmacother ; 25(12): 1707-1716, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39129520

ABSTRACT

BACKGROUND: When considering changing hypnotic pharmacotherapy, lemborexant has attracted attention as a candidate due to its effectiveness and safety profile. However, few studies have investigated switching patterns in clinical practice. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study using a nationwide claims database. Patients prescribed a single hypnotic who either subsequently switched to (switching cohort) or were additionally prescribed (add-on cohort) lemborexant between July 2020 and December 2021 were identified. Proportion of successful switching was defined as remaining on lemborexant alone or without any hypnotic at 6 months after lemborexant initiation. RESULTS: The success proportion was 70.1% in the switching cohort (n = 4,861) and 38.6% in the add-on cohort (n = 9,423). In the add-on cohort, the success proportion was lower in patients with a hypnotic history of ≥180 days (31.4%) and in patients whose prescribed hypnotic was a benzodiazepine or non-benzodiazepine (31.5% and 37.6%, respectively). CONCLUSION: The proportion of successful switching was higher in patients who switched to lemborexant than in those who added lemborexant as a concomitant treatment. The lower success proportion in the add-on cohort might be related to clinically more severe insomnia, and/or a concomitant prescription of benzodiazepine or non-benzodiazepine, from which discontinuation may be challenging.


Subject(s)
Databases, Factual , Hypnotics and Sedatives , Practice Patterns, Physicians' , Sleep Initiation and Maintenance Disorders , Humans , Male , Female , Retrospective Studies , Middle Aged , Hypnotics and Sedatives/therapeutic use , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/adverse effects , Aged , Japan , Adult , Sleep Initiation and Maintenance Disorders/drug therapy , Practice Patterns, Physicians'/statistics & numerical data , Cohort Studies , Drug Therapy, Combination , Drug Substitution/statistics & numerical data , Pyridines/therapeutic use , Pyridines/administration & dosage , Pyridines/adverse effects , Young Adult , Pyrimidines
5.
J Am Geriatr Soc ; 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39134455

ABSTRACT

BACKGROUND: This study aims to evaluate the add-on effects of oral Chinese herbal medicine (CHM) for mild cognitive impairment (MCI), when used in addition to donepezil compared to donepezil alone. METHODS: Randomized controlled trials comparing these treatments across all types of MCI were identified from nine databases and three registers until August 2023. Outcome measures were Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and adverse events (AEs). Methodological quality was assessed using Cochrane risk-of-bias tool, and evidence certainty was evaluated using the GRADE method. RESULTS: Involving 1611 participants across 20 studies, meta-analysis results indicate that oral CHM combined with donepezil significantly improved cognitive function in MCI patients compared to donepezil alone, as evidenced by MMSE (1.88 [1.52, 2.24], I2 = 41%, 12 studies, 993 participants) and MoCA (MD: 2.01 [1.57, 2.44], I2 = 52%, 11 studies, 854 participants). Eleven studies reported details of AEs, identifying gastrointestinal symptoms and insomnia as the most common symptoms. No significant difference in AEs frequency was found between the groups (RR: 0.91 [0.59, 1.39], I2 = 4%, 11 studies, 808 participants). All 20 studies were evaluated as having "some concerns" regarding the overall risk of bias. The certainty of evidence for MMSE was "moderate" and "low" for MoCA. From frequently utilized herbs, two classical CHM formulae were identified: Kai xin san and Si wu decoction. The observed treatment effects of commonly used herbs may be exerted through multiple pharmacological mechanisms, including anti-inflammatory, anti-oxidative stress, anti-apoptotic actions, promotion of neuronal survival and modulation of the cholinergic system. CONCLUSIONS: The concurrent use of oral CHM and donepezil appears to be more effective than donepezil alone in improving the cognitive function of MCI, without leading to an increase in AEs. While recognizing concerns of overall methodological quality, this combined therapy should be considered as an alternative option for clinical practice.

6.
Biochim Biophys Acta Gen Subj ; 1868(10): 130687, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39097174

ABSTRACT

Human glycosyltransferases (GTs) play crucial roles in glycan biosynthesis, exhibiting diverse domain architectures. This study explores the functional diversity of "add-on" domains within human GTs, using data from the AlphaFold Protein Structure Database. Among 215 annotated human GTs, 74 contain one or more add-on domains in addition to their catalytic domain. These domains include lectin folds, fibronectin type III, and thioredoxin-like domains and contribute to substrate specificity, oligomerization, and consequent enzymatic activity. Notably, certain GTs possess dual enzymatic functions due to catalytic add-on domains. The analysis highlights the importance of add-on domains in enzyme functionality and disease implications, such as congenital disorders of glycosylation. This comprehensive overview enhances our understanding of GT domain organization, providing insights into glycosylation mechanisms and potential therapeutic targets.


Subject(s)
Catalytic Domain , Glycosyltransferases , Protein Domains , Humans , Glycosyltransferases/metabolism , Glycosyltransferases/chemistry , Substrate Specificity , Glycosylation , Models, Molecular , Polysaccharides/metabolism , Polysaccharides/chemistry
7.
Front Psychiatry ; 15: 1366942, 2024.
Article in English | MEDLINE | ID: mdl-38957737

ABSTRACT

Introduction: This randomized, placebo-controlled, double-blind, parallel study aimed to evaluate the effect of 3-month supplementation of bovine colostrum (BOV-COL; 8x400 mg per day) on the outcomes of depression treatment in hospitalized patients with substance use disorder (SUD). The hypothesis is that BOV-COL supplementation as an add-on treatment results in favorable alternations in selected blood inflammatory markers or neurotransmitters, leading to better depression treatment outcomes compared with placebo (PLA). Methods: Patients with a Minnesota Multiphasic Personality Inventory-2 score ≥60 points were enrolled. Twenty-nine participants (n=18 in the BOV-COL group and n=11 in the PLA group) completed the protocol. Results: The mean Beck Depression Inventory-II score was significantly reduced after supplementation in both groups. However, the mean 17-point Hamilton Depression Rating Scale score was decreased in the BOV-COL group, but not in the PLA group. In the BOV-COL group, there was a reduction in interleukin (IL)-1, IL-6, IL-10, the IL-6:IL-10 ratio, IL-17, and tumor necrosis factor alpha (TNF-α), while in the PLA group only IL-6 decreased. Favorable alternations in the total count and differentials of white blood cell subsets were more pronounced in the BOV-COL. There were no changes in neurotransmitter concentrations. Conclusions: BOV-COL supplementation is a promising add-on therapy in patients with depression and SUD.

8.
Sci Rep ; 14(1): 16460, 2024 07 16.
Article in English | MEDLINE | ID: mdl-39013989

ABSTRACT

A novel, highly sensitive and eco-friendly micellar-mediated spectrofluorimetric method was developed and validated for the determination of the novel antiparkinsonian drug safinamide mesylate in the presence of its related precursor impurity, 4-hydroxybenzaldehyde. The proposed approach relies on increasing the inherent fluorescence emission at 296 nm of safinamide, by forming hydrogen bonds between the mentioned drug and sodium dodecyl sulfate in the micellar system using 0.1 N HCl as a solvent, following excitation at 226 nm. A thorough investigation was conducted into the experimental factors affecting spectrofluorimetric behavior of the studied drug. A linearity plot of safinamide over the concentration range of 10.0-1000.0 ng/mL against the relative fluorescence intensities was established. The proposed method demonstrated excellent sensitivity down to the nano-gram level with detection and quantitation limits of 1.91 and 5.79 ng/mL, respectively. The studied drug was effectively determined in Parkimedine® Tablets. Furthermore, the proposed method allows for ultrasensitive quantification of safinamide in spiked human plasma, with satisfactory percentage recovery (98.97-102.28%). Additionally, the greenness assessment using the advanced green certificate classification approach, the complementary green analytical procedure index (Complex-GAPI), and the analytical GREEness metric approach (AGREE), along with the practicality check using the Blue Applicability Grade Index in addition to the all-inclusive overall whiteness evaluation using the RGB-12 model were carried out. The outcomes demonstrated the effectiveness and whiteness of the proposed technique. Clearly, the suggested approach has the advantages of being simple, requiring no pretreatment steps, and relying solely on direct measuring procedures.


Subject(s)
Alanine , Antiparkinson Agents , Benzylamines , Micelles , Spectrometry, Fluorescence , Humans , Spectrometry, Fluorescence/methods , Alanine/analogs & derivatives , Alanine/blood , Antiparkinson Agents/blood , Antiparkinson Agents/analysis , Antiparkinson Agents/therapeutic use , Benzylamines/blood , Benzylamines/analysis , Benzylamines/chemistry , Tablets , Limit of Detection , Reproducibility of Results
9.
New Bioeth ; : 215-231, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982760

ABSTRACT

This article reads the uptake of facial-matching algorithms by fertility clinics in Spain through the lens of 'the fertility fix': a software fix to the social reconfiguration of kinship and a fixed capital investment made by competing fertility companies and firms. 'The fertility fix' is proposed as a critical, ethical lens through which to situate algorithmic facial-matching in assisted reproduction in the context of the racial politics of the face and phenotype and the spatial politics of market expansion. While an 'infertility crisis' is often mentioned when explaining the growth of the assisted reproductive technologies (ARTs) industry, the use of donated reproductive cells is tied up in societal, ecological and economic shifts. Combining Software Studies analysis with Marxist Feminist and trans*feminist perspectives on shifting re/production dynamics, the article details the role of computational technologies in promoting certain ideas and beliefs about family and fixing certain territories of capital flow.

10.
J Neurol Sci ; 462: 123106, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38925069

ABSTRACT

INTRODUCTION: Post-stroke epilepsy (PSE) is one of the most common causes of acquired epilepsy. Nevertheless, there is limited evidence regarding the clinical profile of antiseizure medications (ASMs) in PSE. This study aims to evaluate the 12-month effectiveness and tolerability of perampanel (PER) used as only add-on treatment in patients with PSE in a real-world setting. METHODS: We performed a subgroup analysis of PSE patients included in a previous retrospective, longitudinal, multicentre observational study on adults. Treatment discontinuation, seizure frequency and adverse events were collected at 3, 6 and 12 months. Sub-analyses by early (≤1 previous ASM) or late PER add-on were also conducted. RESULTS: Our analysis included 56 individuals with PSE, characterized by varying initial treatment modalities and timeframes relative to disease onset. We found notable retention rates (92.8%, 83.7%, and 69% at 3, 6, and 12 months), with treatment withdrawal mainly due to poor tolerability. One year after PER introduction, seizure frequency significantly reduced, with a responder rate (≥50% reduction) of 83.9% and a seizure-free rate of 51.6%. Adverse events occurred in 25 (46.3%) patients, mainly dizziness, irritability, and behavioural disorders. No major statistical differences were found between early (30 patients, 53.6%) and late add-on groups, except for a higher 6-month responder rate in the early add-on group. CONCLUSION: Adjunctive PER was effective and well-tolerated in patients with PSE in a real-world setting. Perampanel demonstrated good efficacy and safety as both early and late add-on treatment, making it a compelling option for this unique patient population.


Subject(s)
Anticonvulsants , Epilepsy , Nitriles , Pyridones , Stroke , Humans , Pyridones/therapeutic use , Pyridones/adverse effects , Anticonvulsants/therapeutic use , Female , Male , Aged , Middle Aged , Epilepsy/drug therapy , Retrospective Studies , Stroke/complications , Stroke/drug therapy , Longitudinal Studies , Treatment Outcome , Drug Therapy, Combination , Aged, 80 and over , Adult
11.
Epilepsia Open ; 9(4): 1550-1564, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38888005

ABSTRACT

OBJECTIVE: Several antiseizure medications (ASMs) have been approved for the treatment of focal epilepsy. However, there is a paucity of evidence on direct comparison of ASMs. We evaluated the comparative efficacy and safety of all approved add-on ASMs for the treatment of focal epilepsy using network meta-analysis. METHODS: Data through extensive literature search was retrieved from PubMed, Embase, Cochrane, and ClinicalTrial.gov databases using predefined search terms from inception through March 2023. PRISMA reporting guidelines (CRD42023403450) were followed in this study. Efficacy outcomes assessed were ≥50%, ≥75%, and 100% responder rates. Patient retention rate and safety outcomes such as overall treatment-emergent adverse events (TEAEs) and individual TEAEs were assessed. "Gemtc" 4.0.4 package was used to perform Bayesian analysis. Outcomes are reported as relative risks (RRs) and 95% confidence interval (CI). RESULTS: Literature search retrieved 5807 studies of which, 75 studies were included in the analysis. All ASMs showed significantly higher ≥50% responder rate compared with placebo. Except the ≥75% seizure frequency reduction for zonisamide (2.23; 95% CI: 1.00-5.70) and 100% for rufinamide (2.03; 95% CI: 0.54-11.00), all other interventions showed significantly higher ≥75% and 100% responder rates compared with placebo. Among treatments, significantly higher 100% responder rate was observed with cenobamate compared to eslicarbazepine (10.71; 95% CI: 1.56-323.9) and zonisamide (10.63; 95% CI: 1.37-261.2). All ASMs showed a lower patient retention rate compared to placebo, with the least significant value observed for oxcarbazepine (0.77; 95% CI: 0.7-0.84). Levetiracetam showed a lower risk of incidence (1.0; 95%CI: 0.94-1.1; SUCRA: 0.885067) for overall TEAE compared with other medications. SIGNIFICANCE: All approved ASMs were effective as add-on treatment for focal epilepsy. Of the ASMs included, cenobamate had the greatest likelihood of allowing patients to attain seizure freedom. PLAIN LANGUAGE SUMMARY: This article compares the efficacy and safety of antiseizure medications (ASMs) currently available to neurologists in the treatment of epileptic patients. Several newer generation ASMs that have been developed may be as effective or better than the older medications. We included 75 studies in the analysis. In comparison, all drugs improved ≥50%, ≥75% and 100% responder rates compared to control, except for Zonisamide and Rufinamide in the ≥75% and 100% responder rate categories. Retention of patients undergoing treatment was lower in drugs than placebo. All drugs were tolerated, the levetiracetam showed the best tolerability. Cenobamate more likely help completely to reduce seizures.


Subject(s)
Anticonvulsants , Epilepsies, Partial , Network Meta-Analysis , Humans , Anticonvulsants/therapeutic use , Anticonvulsants/adverse effects , Anticonvulsants/administration & dosage , Epilepsies, Partial/drug therapy , Drug Therapy, Combination , Treatment Outcome
12.
Cureus ; 16(5): e59663, 2024 May.
Article in English | MEDLINE | ID: mdl-38836150

ABSTRACT

Worldwide, cardiovascular diseases (CVDs) are still the primary cause of death, and there are notable differences between sexes when it comes to symptoms/course and treatment. Due to evolving healthcare technologies, significant progress has been made in understanding CVDs. Hence, it is evident that gender disparities exist in the clinical presentation, prevalence, management, outcomes, and risk factors, including biological, behavioral, and sociocultural factors. This narrative review is designed to provide a generalized idea of gender disparities in CVDs. It aims to provide insights to prove the role of hormonal influences, genetic predispositions, and the difference in physiological outcomes owing to different genders. This review explores subtle distinctions in CVD across genders, including changes in structure, biology, and hormones that affect how illness presents and progresses. Lifestyle variables also influence sociocultural factors and gender disparities in risk profiles. Traditional risk factors, diabetes mellitus (DM), cholesterol levels, and smoking may have different weights and relevance in men and women. Moreover, age and other conventional risk variables have distinct effects on gender. Treatment efficacy may be impacted by the expression of gender-specific factors, emphasizing the necessity for customized strategies. Development of CVDs can be delayed or prevented, and its consequences can be lessened with the early identification and effective management of gender-specific factors. More investigation is necessary to clarify complex interactions between structural, biochemical, and hormonal aspects across genders in order to maximize treatment results and reduce the burden of CVDs.

13.
Neurol Sci ; 45(9): 4519-4527, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38558319

ABSTRACT

BACKGROUND: Antiseizure medications remain the cornerstone of treatment for epilepsy, although a proportion of individuals with the condition will continue to experience seizures despite appropriate therapy. Treatment choices for epilepsy are based on variables related to both the individual patient and the available medications. Brivaracetam is a third-generation agent antiseizure medication. METHODS: We carried out a Delphi consensus exercise to define the role of brivaracetam in clinical practice and to provide guidance about its use as first add-on ASM and in selected clinical scenarios. A total of 15 consensus statements were drafted by an expert panel following review of the literature and all were approved in the first round of voting by panelists. The consensus indicated different clinical scenarios for which brivaracetam can be a good candidate for treatment, including first add-on use. RESULTS: Overall, brivaracetam was considered to have many advantageous characteristics that render it a suitable option for patients with focal epilepsy, including a fast onset of action, favorable pharmacokinetic profile with few drug-drug interactions, broad-spectrum activity, and being well tolerated across a range of doses. Brivaracetam is also associated with sustained clinical response and good tolerability in the long term. CONCLUSIONS: These characteristics also make it suitable as an early add-on for the elderly and for patients with post-stroke epilepsy or status epilepticus as highlighted by the present Delphi consensus.


Subject(s)
Anticonvulsants , Consensus , Delphi Technique , Epilepsies, Partial , Pyrrolidinones , Humans , Pyrrolidinones/therapeutic use , Pyrrolidinones/administration & dosage , Anticonvulsants/therapeutic use , Anticonvulsants/administration & dosage , Epilepsies, Partial/drug therapy , Drug Therapy, Combination
14.
Pharmacol Ther ; 258: 108649, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38615798

ABSTRACT

Current epidemiological data estimate that one in five people suffers from chronic pain with considerable impairment of health-related quality of life. The pharmacological treatment is based on first- and second-line analgesic drugs, including COX-2 selective and nonselective nonsteroidal anti-inflammatory drugs, paracetamol, antidepressants, anti-seizure drugs and opioids, that are characterized by important side effects. N-palmitoylethanolamine (PEA) is a body's own fatty-acid ethanolamide belonging to the family of autacoid local injury antagonist amides. The anti-inflammatory and pain-relieving properties of PEA have been recognized for decades and prompted to depict its role in the endogenous mechanisms of pain control. Together with its relative abundance in food sources, this opened the way to the use of PEA as a pain-relieving nutritional intervention. Naïve PEA is a large particle size lipid molecule with low solubility and bioavailability. Reducing particle size is a useful method to increase surface area, thereby improving dissolution rate and bioavailability accordingly. Micron-size formulations of PEA (e.g., ultramicronized and co-(ultra)micronized) have shown higher oral efficacy compared to naïve PEA. In particular, ultramicronized PEA has been shown to efficiently cross the intestinal wall and, more importantly, the blood-brain and blood-spinal cord barrier. Several preclinical and clinical studies have shown the efficacy, safety and tolerability of ultramicronized PEA. This narrative review summarizes the available pharmacokinetic/pharmacodynamic data on ultramicronized PEA and focuses to its contribution to pain control, in particular as 'add-on' nutritional intervention. Data showing the ability of ultramicronized PEA to limit opioid side effects, including the development of tolerance, have also been reviewed.


Subject(s)
Analgesics , Chronic Pain , Ethanolamines , Palmitic Acids , Ethanolamines/adverse effects , Ethanolamines/therapeutic use , Palmitic Acids/therapeutic use , Palmitic Acids/pharmacology , Palmitic Acids/adverse effects , Humans , Analgesics/adverse effects , Analgesics/pharmacology , Chronic Pain/drug therapy , Animals , Amides , Particle Size , Biological Availability
15.
Clin Chem Lab Med ; 62(9): 1835-1844, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-38593236

ABSTRACT

OBJECTIVES: Integration of add-on testing in high-scale automated clinical laboratories constitute a valuable instrument not only for the clinicians and the general patient care, but also for the laboratory itself. Knowledge on sample quality and analytical stability upon storage is necessary to be able to offer add-on testing. The objectives of this study were to examine the analytical stability of 63 biochemical analytes in plasma and urine samples stored at 16 °C. METHODS: Samples were collected by professional laboratory technicians, analyzed at automated analyzers and stored in their primary, capped tube without separator for 10, 12, 16, 20 or 24 h at 16 °C. Stability was assessed by inspecting mean concentration of samples at baseline and examining if (A) mean concentration over time violated limits of bias, or if (B) individual sample concentrations violated limits of total error. RESULTS: The majority of the 63 analytes were stable for up to 24 h of storage. Few of the analytes were only suitable for add-on testing for 4, 6, 10, 12, 16 or 20 h of storage. One analyte, P-lactate dehydrogenase, was not found suitable for add-on testing when stored at 16 °C. CONCLUSIONS: Due to the increasing number of intelligent solutions for high-scale clinical laboratories, add-on testing has come to stay. Loss of stability could not be demonstrated for the majority of analytes after 10, 12, 16, 20 or 24 h of storage. This feature of analytical stability suggests that add-on testing is an acceptable tool for these analytes.


Subject(s)
Specimen Handling , Humans , Specimen Handling/standards , Temperature , Time Factors
16.
Diabetes Obes Metab ; 26(7): 2830-2838, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38602409

ABSTRACT

AIM: To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.


Subject(s)
Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Glycated Hemoglobin , Hypoglycemic Agents , Metformin , Adult , Aged , Female , Humans , Male , Middle Aged , Blood Glucose/drug effects , Blood Glucose/metabolism , China , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Double-Blind Method , East Asian People , Glycated Hemoglobin/analysis , Glycated Hemoglobin/metabolism , Glycated Hemoglobin/drug effects , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Metformin/therapeutic use , Metformin/administration & dosage , Treatment Outcome
17.
Biochem Med (Zagreb) ; 34(2): 020704, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38665870

ABSTRACT

Introduction: Clinical laboratories should guarantee sample stability in specific storage conditions for further analysis. The aim of this study is to evaluate the stability of plasma samples under refrigeration for 29 common biochemical analytes usually ordered within an emergency context, in order to determine the maximum allowable period for conducting add-on testing. Materials and methods: A total of 20 patient samples were collected in lithium heparin tubes without gel separator. All analyses were performed using Alinity systems (Abbott Laboratories, Abbott Park, USA) and samples were stored at 2-8 °C. Measurements were conducted in primary plasma tubes at specific time points up to 48 hours, with an additional stability study in plasma aliquots extending the time storage up to 96 hours. The stability limit was estimated considering the total limit of change criteria. Results: Of the 29 studied parameters, 24 demonstrated stabilities within a 48-hour storage period in primary plasma tubes. However, five analytes: aspartate aminotransferase, glucose, lactate dehydrogenase, inorganic phosphate and potassium evidenced instability at different time points (7.9 hours, 2.7 hours, 2.9 hours, 6.2 hours and 4.7 hours, respectively). The stability study in plasma aliquots showed that all parameters remained stable for 96 hours, except lactate dehydrogenase, with a stability limit of 63 hours. Conclusions: A reduced stability of primary plasma samples was observed for five common biochemical analytes ordered in an emergency context. To ensure the quality of add-on testing for these samples, plasma aliquots provide stability for a longer period.


Subject(s)
Blood Specimen Collection , Humans , Blood Specimen Collection/standards , Blood Chemical Analysis/standards , Quality Control , Quality Assurance, Health Care , Aspartate Aminotransferases/blood , L-Lactate Dehydrogenase/blood , Plasma/chemistry , Specimen Handling/standards
18.
Prz Gastroenterol ; 19(1): 60-66, 2024.
Article in English | MEDLINE | ID: mdl-38571541

ABSTRACT

Introduction: The primary objective was to demonstrate the efficacy and safety of itopride as an add-on therapy to a proton pump inhibitor (PPI) in the treatment of gastroesophageal reflux disease. Aim: Reflux disease affects the largest percentage of the population worldwide, symptoms overlap with many other conditions which hamper diagnostic and therapy presenting challenges in treating patients and prompting an intensive search for new, more effective therapeutic regimens. Material and methods: A retrospective study was undertaken with 140 enrolled patients with reflux disease, confirmed by 24-hour pH impedance previously treated with PPIs without any significant improvement. Itopride was added to the PPI therapy in a dose of 150 mg/day, after which the severity of reflux disease symptoms was reassessed. Results: The greatest improvement after the combined treatment (p < 0.001) was experienced in the context of heartburn, nausea and laryngopharyngeal symptoms. There was also a high percentage of statistically significant (p < 0.01) improvement in burning in the oesophagus and stomach and regarding postprandial fullness, gastric retention and swallowing disorders. No adverse effects were noted. Conclusions: The presented study clearly demonstrates that in patients ineffectively treated with PPIs, the addition of itopride to the therapy for 8 weeks without changing the PPI dose, significantly improves the efficacy of treatment of reflux disease and thus shortens the need for medication usage and reduces the costs of therapy, potential side effects of PPI, improves the patient's quality of life and decreases the frequency of medical appointments.

19.
Lab Med ; 55(5): 585-589, 2024 Sep 04.
Article in English | MEDLINE | ID: mdl-38431798

ABSTRACT

BACKGROUND: Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages. METHODS: This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics. RESULTS: A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing. CONCLUSION: Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.


Subject(s)
Emergency Service, Hospital , Phlebotomy , Humans , Cross-Sectional Studies , Emergency Service, Hospital/statistics & numerical data , Phlebotomy/methods , Phlebotomy/statistics & numerical data , COVID-19/epidemiology , COVID-19/diagnosis , Specimen Handling/methods , Blood Specimen Collection/methods , Blood Specimen Collection/standards , Pandemics , Surveys and Questionnaires , Urine Specimen Collection/methods
20.
Heliyon ; 10(6): e27770, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38500981

ABSTRACT

Objective: This study aimed to assess the treatment compliance, patterns, healthcare resource utilization (HCRU), and costs of anti-epilepsy drugs (AEDs) as the first add-on therapy in patients with epilepsy. Methods: We conducted a retrospective population-based cohort study using Korean National Health Insurance claims data from 2016 to 2020. Patients with epilepsy who newly received AED add-on therapy were identified and followed for up to 12 months to evaluate persistence, adherence, treatment patterns, HCRU, and costs. Results: Among 6,746 patients who initiated AED add-on therapy, 65.5% were persistent on their index AED add-on from the index date until the end of the follow-up period, and the mean persistent time on the index add-on was 307.3 ± 92.3 days. A total of 76.8% patients were adherent, with a medication possession ratio (MPR) ≥80%, and the mean MPR was 88.9 ± 25.4%. Persistence and adherence to the index AED add-on were relatively higher among patients prescribed lamotrigine, levetiracetam, oxcarbazepine, and perampanel than those prescribed carbamazepine, topiramate, or valproate. A total of 41.0% of the patients changed their index AED add-on during the follow-up period. The carbamazepine, topiramate, and valproate groups had higher rates of change than the other AED groups. HCRU and costs tended to be lower in the lamotrigine, levetiracetam, oxcarbazepine, and perampanel groups. Furthermore, perampanel showed the lowest HCRU and costs for all-cause cases as well as the lowest length of stay and outpatient visits for epilepsy-related cases. Conclusion: In this population-based study, the use of lamotrigine, levetiracetam, oxcarbazepine, or perampanel as the first add-on therapy in patients with epilepsy contributed to better treatment compliance and lower HCRU and costs than that of carbamazepine, topiramate, or valproate.

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