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The Journal of Clinical Psychiatry Jun 2024To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants. In this... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Esmethadone (REL-1017) in Patients With Major Depressive Disorder and Inadequate Response to Standard Antidepressants: A Phase 3 Randomized Controlled Trial.
To test esmethadone (REL-1017) as adjunctive treatment in patients with major depressive disorder (MDD) and inadequate response to standard antidepressants. In this phase 3, double-blind, placebo-controlled trial, outpatients with MDD () were randomized to daily oral esmethadone (75 mg on day 1, followed by 25 mg daily on days 2 through 28) or placebo between December 2020 and December 2022. The primary efficacy measure was change from baseline (CFB) to day 28 in the Montgomery-Asberg Depression Rating Scale (MADRS) score. The intent-to-treat (ITT) population included all randomized participants. The per-protocol (PP) population included completers without major protocol deviations impacting assessment. Post hoc analyses included participants with severe depression (baseline MADRS score ≥35). For the ITT analysis (n = 227), mean CFB was 15.1 (SD 11.3) for esmethadone (n = 113) and 12.9 (SD 10.4) for placebo (n = 114), with a mean difference (MD) of 2.3, which was not statistically significant ( = .154; Cohen effect size [ES] = 0.21). Remission rates were 22.1% and 13.2% ( = .076), and response rates were 39.8% and 27.2% ( = .044) with esmethadone and placebo, respectively. For the PP analysis (n = 198), mean CFB was 15.6 (SD 11.2) for esmethadone (n = 101) and 12.5 (SD 9.9) for placebo (n = 97), with an MD of 3.1 ( = .051; ES =0.29). In post hoc analyses of patients with baseline MADRS ≥35 in the ITT population (n = 112), MD was 6.9; = .0059; ES = 0.57, and for the PP population (n = 98), MD was 7.9; = .0015; ES = 0.69. Adverse events (AEs) were predominantly mild or moderate and transient, with no significant differences between groups. The primary end point was not met. Esmethadone showed stronger efficacy in PP than in ITT analyses, with the discrepancy not attributable to AEs impacting treatment adherence. Significant efficacy occurred in post hoc analyses of patients with severe depression. Esmethadone was well tolerated, consistent with prior studies. ClinicalTrials.gov identifier: NCT04688164.
Topics: Humans; Depressive Disorder, Major; Male; Adult; Female; Double-Blind Method; Middle Aged; Antidepressive Agents; Depressive Disorder, Treatment-Resistant; Treatment Outcome; Drug Therapy, Combination
PubMed: 38917366
DOI: 10.4088/JCP.24m15265 -
Rhode Island Medical Journal (2013) Jul 2024The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell... (Review)
Review
The molecular pathogenesis of exocrine pancreatic cancer involves mutations K-RAS, TP53, CDKN2A, and SMAD4. The KRAS oncogene leads to constitutively active tumor cell proliferation and is present in 90% of unresectable or metastatic pancreatic adenocarcinomas. Of these, the G12C variant of K-RAS genes accounts for 1-2% of mutations. A 65-year-old woman initially diagnosed with T3N0M0 pancreatic adenocarcinoma, underwent six cycles of neoadjuvant chemotherapy with mFOLFIRINOX followed by Whipple procedure. Her pathological stage was T4N2. She then received adjuvant mFOLFIRINOX but unfortunately her disease progressed through multiple lines of chemotherapy. Molecular analysis by Next Generation Sequence(NGS) panel revealed KRAS G12C mutation. Based on this mutational status, she was started on Sotorasib to which she had clinical response lasting for about 11 months prior to disease progression. Off-label use of Sotorasib as fourth-line treatment in our patient with KRAS G12C mutated pancreatic cancer was efficacious and relatively well tolerated.
Topics: Humans; Pancreatic Neoplasms; Female; Aged; Adenocarcinoma; Triazoles; Antineoplastic Combined Chemotherapy Protocols; Proto-Oncogene Proteins p21(ras); Pyrimidines; Mutation; Antineoplastic Agents; Irinotecan; Oxaliplatin; Fluorouracil; Leucovorin; Off-Label Use; Piperazines; Pyridines
PubMed: 38917307
DOI: No ID Found -
PloS One 2024Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and...
Study protocol for ADHERE (Applying Directly observed therapy to HydroxyurEa to Realize Effectiveness): Using small business partnerships to deliver a scalable and novel hydroxyurea adherence solution to youth with sickle cell disease.
Sickle cell disease (SCD) is an inherited blood disorder that affects approximately 100,000 Americans, primarily from underrepresented racial minority populations, and results in costly, multi-organ complications. Hydroxyurea, the primary disease-modifying therapy for SCD, is effective at reducing most complications; however, adherence to hydroxyurea remains suboptimal and is the primary barrier to clinical effectiveness. Video directly observed therapy (VDOT) has shown promise as an adherence-promoting intervention for hydroxyurea, yet previous VDOT trials were limited by high attrition from gaps in technology access, use of unvalidated adherence measures, and healthcare system limitations of delivering VDOT to patients. As such, we fostered a small business partnership to compare VDOT for hydroxyurea to attention control to address previous shortcomings, promote equitable trial participation, and maximize scalability. VDOT will be administered by Scene Health (formerly emocha Health) and adherence monitoring will be performed using a novel electronic adherence monitor developed to meet the unique needs of the target population. Adolescent and young adult patients as well as caregivers of younger patients (<11 years of age) will be recruited. In addition to visit incentives, all participants will be offered a smartphone with a data plan to ensure all participants have equal opportunity to complete study activities. The primary objectives of this pilot, multi-center, randomized controlled trial (RCT) are to assess retention and sustained engagement and to explore needs and preferences for longer-term adherence monitoring and interventions. This RCT is registered with the National Institutes of Health (NCT06264700). Findings will inform a future efficacy RCT applying VDOT to hydroxyurea to address adherence gaps and improve outcomes within this vulnerable population.
Topics: Humans; Anemia, Sickle Cell; Hydroxyurea; Adolescent; Child; Medication Adherence; Young Adult; Antisickling Agents; Male; Female; Adult
PubMed: 38917111
DOI: 10.1371/journal.pone.0304644 -
PloS One 2024Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have...
Study protocol for the development and validation of a questionnaire evaluating predisposition to immunosuppressant medication non-adherence of kidney pre-transplant patients. The KATITA project.
Non-adherence to immunosuppressive medication after kidney transplant is an important cause of graft rejection and loss. Approaches to minimization of non-adherence have focused on the identification of episodes of medication non-adherence, but by then irreparable harm to the graft may already have occurred, and a more effective approach would be to adopt preventive measures in patients who may have difficulty in adhering to medication. The aim of this study protocol is to develop and validate a clinical questionnaire for assessing, in kidney transplant candidate patients in the pre-transplant setting, the predisposition to non-adherence to immunosuppressive medication. In this multicenter, prospective study, a pilot questionnaire in Brazilian Portuguese language, composed of Likert-scaled statements expressing patients' beliefs, behaviors and barriers regarding medication taking will be assembled from a literature review, from focus groups, and an expert panel. The pilot questionnaire will be administered to a minimum of 300 patients in kidney transplant waiting lists and exploratory factor analysis will be used for development of the definitive questionnaire. A random subsample of a minimum of 60 patients will have the scale re-administered after one month for evaluation of test-retest reliability. A multicenter, external validation study will include 364 kidney transplant candidates who will be evaluated immediately before surgery and at months 3, 6 and 12 post-transplant for assessment of concurrent validity, by comparison with two scales that assess medication non-adherence, and for determination of predictive validity using a triangulation method for assessment of medication non-adherence. Structural validity will be assessed with confirmatory factor analysis using structural equation modeling. Cross-cultural generalizability and validity will be assessed by a multicenter study, in which a translation of the scale to another language will be administered to kidney transplant candidate patients from a different culture, with a subsample being selected for test-retest. This study will be conducted in Spain with a Spanish translation of the scale.
Topics: Humans; Kidney Transplantation; Immunosuppressive Agents; Surveys and Questionnaires; Medication Adherence; Prospective Studies; Reproducibility of Results; Graft Rejection; Pilot Projects; Female; Male
PubMed: 38917103
DOI: 10.1371/journal.pone.0305953 -
Supportive Care in Cancer : Official... Jun 2024Adherence to oral anticancer treatments (OATs) is a critical issue in metastatic breast cancer (MBC) to enhance survivorship and quality of life. The study is aimed to... (Observational Study)
Observational Study
PURPOSE
Adherence to oral anticancer treatments (OATs) is a critical issue in metastatic breast cancer (MBC) to enhance survivorship and quality of life. The study is aimed to analyze the main themes and attributes related to OATs in MBC patients. This research is part of a project titled "Enhancing Therapy Adherence Among Metastatic Breast Cancer Patients" designed to produce a predictive model of non-adherence, a decision support system, and guidelines to improve adherence to OATs.
METHODS
The study consists of an exploratory observational and qualitative analysis using a focus group method. A semi-structured interview guide was developed to handle relevant OAT themes. Wordcloud plots, network analysis, and sentiment analysis were performed.
RESULTS
Nineteen female MBC patients participated in the protocol (age mean 55.95, SD = 6.87). Four main themes emerged: (theme 1) individual clinical pathway; (theme 2) barriers to adherence; (theme 3) resources to adherence; (theme 4) patients' perception of new technologies. The Wordcloud and network analysis highlighted the important role of treatment side effects and the relationship with the clinician in the modulation of adherence behavior. This result is consistent with the sentiment analysis underscoring patients experience fear of issues related to clinical values and ineffective communication and discontinuity of the doctor in charge of the patient care.
CONCLUSION
The study highlighted the key role of the individual, relational variables, and side effects as internal and external determinants influencing adherence to MBC. Finally, the opportunity offered by eHealth technology to connect with other patients with similar conditions and share experiences could be a relief for MBC patients.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Medication Adherence; Administration, Oral; Antineoplastic Agents; Focus Groups; Neoplasm Metastasis; Aged; Qualitative Research; Quality of Life
PubMed: 38916761
DOI: 10.1007/s00520-024-08639-4 -
European Journal of Anaesthesiology Jun 2024Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend...
BACKGROUND
Drug challenge is the gold standard for identifying causative agents of drug allergies. Although clinical guidelines have recently been published, they do not recommend neuromuscular blocking agent (NMBA) drug challenges. NMBA challenges are rendered difficult by the lack of homogeneity of routine allergy work-ups and the necessity of a specialised setting. Several scenarios support NMBA challenges, such as an ambiguous allergy work-up, a high suspicion of a false-positive skin test or identification of a well tolerated alternative NMBA strategy. Furthermore, routine allergy work-ups may not recognise non-IgE mechanisms, such as IgG or MRGPRX2, whereas drug challenges may reveal them. Finally, if the culprit NMBA is not identified, subsequent anaesthesia regimens will be challenging to implement, resulting in increased risk.
OBJECTIVES
This literature review discusses the indications, strategies, doses, monitoring methods, limitations, and unresolved issues related to drug challenges for NMBAs.
DESIGN
The literature review included randomised controlled trials, observational studies, reviews, case reports, series, and comments on humans.
DATA SOURCES
Studies were retrieved from databases (PubMed) and electronic libraries (OVID, EMBASE, Scopus, etc.).
ELIGIBILITY CRITERIA
All studies that referred to the NMBA challenge were included without publication date limitations.
RESULTS
NMBA challenge may be considered in NMBA anaphylaxis patients with inconclusive or ambivalent IgE diagnostic work-up under controlled conditions (presence of anaesthetists and allergists with continuous monitoring in a secured environment). To illustrate its utility, a case report of a double NMBA challenge in a patient with NMBA cross-reactivity is presented, along with biological explorations to detect subclinical cellular activation, a novel aspect of this procedure.
CONCLUSION
Drug challenges could be implemented during the NMBA allergy work-up under strict safety conditions at specialised centres with close collaboration between anaesthetists and allergists. This could decrease uncertainty and contribute to defining a safer strategy for subsequent anaesthetic drug regimens.
PubMed: 38916219
DOI: 10.1097/EJA.0000000000002033 -
Cureus May 2024The development of ceramic brackets in orthodontics three decades ago emerged as a response to the increasing patient demand for less visible orthodontic... (Review)
Review
The development of ceramic brackets in orthodontics three decades ago emerged as a response to the increasing patient demand for less visible orthodontic appliances. While these brackets provide superior aesthetics, they are characterized by lower fracture toughness and higher bond strength in contrast to metal brackets. These properties present challenges during the debonding step, including the risk of enamel micro-fractures and cracks. Historically, various strategies have been developed to address challenges associated with debonding, reduce patient discomfort, and ensure that the bond failure site is confined to the bracket-adhesive interface. This included the use of specially designed debonding pliers, electrothermal debonding, ultrasonic technique, and chemical agents. Recently, there has been a shift towards utilizing different types of laser irradiation for this purpose. The burgeoning strategy, however, requires diligent scientific scrutiny to establish a standardized protocol with particular laser parameters and ultimately achieve the goal of enhancing the patient experience by reducing discomfort. This article offers a narrative review of laser-aided debonding of ceramic brackets, aimed at comparing different laser types, presenting their benefits and downsides, validating the efficiency of each method, and summarizing the published literature on this subject. It also provides insights for orthodontists on reducing patient discomfort that usually accompanies debonding ceramic brackets by delving into the science behind the use of lasers for this purpose.
PubMed: 38915986
DOI: 10.7759/cureus.61050 -
Cureus May 2024Ozone has been used as an antibacterial agent for various purposes in healthcare. The use of ozone in dental practice is also well-established. Its utilization as a... (Review)
Review
Ozone has been used as an antibacterial agent for various purposes in healthcare. The use of ozone in dental practice is also well-established. Its utilization as a mouth rinse needs to be explored for further application in clinical practice, especially for cases of gingivitis, a common complaint. This systematic review aims to analyze the literature on the effects of ozonated water in managing gingival inflammation and bleeding across diverse populations. A systematic search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted in PubMed, MEDLINE, Embase, and Cochrane. Studies published between January 2012 and December 2023 employing ozonated water as a treatment for gingivitis or gingival bleeding were included. Five studies met the inclusion criteria, demonstrating the varied efficacy of ozonated water. While some studies showed promising results in reducing bleeding and gingival inflammation, others indicated limitations compared to chlorhexidine. Methodological heterogeneity and lack of standardization were notable. The evidence suggests potential benefits of ozonated water in managing gingival inflammation and bleeding, but methodological variations hinder conclusive findings. Long-term studies with larger sample sizes and standardized protocols are needed to establish the effectiveness of ozonated water as an adjunctive therapy for gingival health.
PubMed: 38915955
DOI: 10.7759/cureus.61006 -
Clinical Kidney Journal Jun 2024The aim of this work was to create and evaluate a preoperative non-contrast-enhanced (CE) magnetic resonance imaging (MRI)/angiography (MRA) protocol to assess renal...
BACKGROUND
The aim of this work was to create and evaluate a preoperative non-contrast-enhanced (CE) magnetic resonance imaging (MRI)/angiography (MRA) protocol to assess renal function and visualize renal arteries and any abnormalities in potential living kidney donors.
METHODS
In total, 28 subjects were examined using scintigraphy to determine renal function. In addition, 3D-pseudocontinuous arterial spin labeling (pCASL), a 2D-non-CE electrocardiogram-triggered radial quiescent interval slice-selective (QISS-MRA), and 4D-CE time-resolved angiography with interleaved stochastic trajectories (CE-MRA) were performed to assess renal perfusion, visualize renal arteries and detect any abnormalities. Two glomerular filtration rates [described by Gates (GFR) and according to the Chronic Kidney Disease Epidemiology Collaboration formula (GFR)]. The renal volumes were determined using both MRA techniques.
RESULTS
The mean value of regional renal blood flow (rRBF) on the right side was significantly higher than that on the left. The agreements between QISS-MRA and CE-MRA concerning the assessment of absence or presence of an aberrant artery and renal arterial stenosis were perfect. The mean renal volumes measured in the right kidney with QISS-MRA were lower than the corresponding values of CE-MRA. In contrast, the mean renal volumes measured in the left kidney with both MRA techniques were similar. The correlation between the GFR and rRBF was compared in the same manner as that between GFR and rRBF.
CONCLUSION
The combination of pCASL and QISS-MRA constitute a reliable preoperative protocol with a total measurement time of <10 min without the potential side effects of gadolinium-based contrast agents or radiation exposure.
PubMed: 38915436
DOI: 10.1093/ckj/sfae101 -
Journal of Pharmacy & Pharmaceutical... 2024Treatment for diabetes includes anti-diabetic medication in addition to lifestyle improvements through diet and exercise. In Japan, protocol-based pharmacotherapy...
Investigating the effect of prescribing status and patient characteristics on the therapeutic outcomes in patients with diabetes using a leftover drug adjustment protocol.
Treatment for diabetes includes anti-diabetic medication in addition to lifestyle improvements through diet and exercise. In Japan, protocol-based pharmacotherapy management allows drug treatment to be provided through cooperation between physicians and pharmacists, based on a protocol that is prepared and agreed upon in advance. However, there are no studies to clarify the relationship between patient characteristics and therapeutic effects after pharmacist intervention in protocol-based pharmacotherapy management for patients with diabetes. Therefore, this study aimed to use protocol-based reports from pharmacies to understand the status of outpatient diabetes medication compliance. We classified patients with diabetes on the basis of patient characteristics that can be collected in pharmacies and investigated the characteristics that impacted diabetes treatment. Patients were prescribed oral anti-diabetic drugs at outpatient clinics of Hitachinaka General Hospital, Hitachi, Ltd., from April 2016 to March 2021. Survey items included patient characteristics (sex, age, number of drugs used, observed number of years of anti-diabetic drug prescription, number of anti-diabetic drug prescription days, and presence or absence of leftover anti-diabetic drugs) and HbA1c levels. Graphical analyses indicated the relationship between each categorised patient characteristic using multiple correspondence analyses. Subsequently, the patients were clustered using K-means cluster analysis based on the coordinates obtained for each patient. Patient characteristics and HbA1c values were compared between the groups for each cluster. A total of 1,910 patients were included and classified into three clusters, with clusters 1, 2, and 3 containing 625, 703, and 582 patients, respectively. Patient characteristics strongly associated with Cluster 1 were ages between 65 and 74 years, use of three or more anti-diabetic drugs, use of 3 years or more of anti-diabetic drugs, and leftover anti-diabetic drugs. Furthermore, Cluster 1 had the highest number of patients with worsening HbA1c levels compared with other clusters. Using the leftover drug adjustment protocol, we clarified the patient characteristics that affected the treatment course. We anticipate that through targeted interventions in patients exhibiting these characteristics, we can identify those who are irresponsibly continuing with drug treatment, are not responding well to therapy, or both. This could substantially improve the efficacy of their anti-diabetic care.
Topics: Humans; Male; Female; Hypoglycemic Agents; Aged; Middle Aged; Diabetes Mellitus; Treatment Outcome; Drug Prescriptions; Glycated Hemoglobin; Pharmacists; Medication Adherence; Japan; Aged, 80 and over; Adult
PubMed: 38915418
DOI: 10.3389/jpps.2024.12886