Clinical Evidence Research Articles

Benign polymorphisms in the BRCA genes with linkage disequilibrium is associated with cancer characteristics.

Germline pathogenic mutation of the BRCA gene increases the prevalence of breast cancer. Reports on the benign variants of BRCA genes are limited. However, the definition of these variants might be altered with the accumulation of clinical evidence. Therefore, in the present study, we focused on benign single nucleotide polymorphisms (SNPs) of BRCA genes. Linkage disequilibrium was calculated from whole genome sequencing of the BRCA genes obtained from 500 healthy controls and 49 breast cancer patients. Sanger sequencing was used to confirm the mutation. The linkage disequilibrium was noted for seven and three SNPs in the BRCA1 and BRCA2 genes, respectively. Breast cancer with BRCA1/2 linkage disequilibrium was not correlated with a personal history of benign diseases or family history of cancer. Nevertheless, breast cancer with BRCA1 linkage disequilibrium was correlated with high tumor-infiltrating lymphocytes and positive extensive intraductal components. The patients with BRCA1 linkage disequilibrium tended to have worse disease-specific survival. Cancers with BRCA2 linkage disequilibrium are associated with a lower ratio of grade III cancer. Moreover, patients with BRCA2 linkage disequilibrium tended to have better overall survival. In conclusion, linkage disequilibrium from benign SNPs of the BRCA genes potentially affects cancer characteristics.

Comparative Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Elderly Patients With Severe Symptomatic Aortic Stenosis: A Systematic Review.

Aortic stenosis is the most common valvular heart disease globally; while transcatheter aortic valve replacement (TAVR) has proven to be a competitive alternative to surgical aortic valve replacement (SAVR) and revolutionized treatment, its safety and efficacy has yet to be comprehensively assessed against SAVR for certain subsets of aortic stenosis patients; therefore, this study aims to systematically analyze all the available clinical evidence from randomized clinical trials on TAVR versus SAVR among intermediate and low-risk patients with severe symptomatic aortic stenosis. We performed a systematic review of the randomized controlled trials (RCT), studies comparing TAVR and SAVR in low- and intermediate-risk patients were identified by a comprehensive search of the major databases. Mortality, stroke, length of stay, and other perioperative outcomes were assessed. A comprehensive screening of 14,384 records identified 9 studies, encompassing 8884 patients with a mean age of 77.76 years and 49.47% male. TAVR demonstrated a significantly lower all-cause mortality at both 30 days and 1 year compared to SAVR, with comparable outcomes at 2 years, underscoring its potential for enhanced survival. Stroke incidence was markedly lower with TAVR at both 30 days and 1 year, highlighting its favorable neurological safety profile. Additionally, TAVR showed a reduced rate of myocardial infarction within the initial 30 days post-procedure. Prosthetic valve endocarditis rates remained low and comparable between the two approaches at both 30 days and 1 year. Notably, TAVR was associated with a significantly shorter hospital stay, suggesting a faster recovery trajectory and improved patient throughput. These findings collectively emphasize the superior efficacy and safety profile of TAVR over SAVR. TAVR may serve as a viable therapeutic option for intermediate and low-risk patients with severe symptomatic aortic stenosis. Future research should focus on long-term outcomes and TAVR device durability, especially in younger, lower-risk populations.

Cancer cell-selective induction of mitochondrial stress and immunogenic cell death by PT-112 in human prostate cell lines

PT-112 is a novel immunogenic cell death (ICD)-inducing small molecule currently under Phase 2 clinical development, including in metastatic castration-resistant prostate cancer (mCRPC), an immunologically cold and heterogeneous disease state in need of novel therapeutic approaches. PT-112 has been shown to cause ribosome biogenesis inhibition and organelle stress followed by ICD in cancer cells, culminating in anticancer immunity. In addition, clinical evidence of PT-112-driven immune effects has been observed in patient immunoprofiling. Given the unmet need for immune-based therapies in prostate cancer, along with a Phase I study (NCT#02266745) showing PT-112 activity in mCRPC patients, we investigated PT-112 effects in a panel of human prostate cancer cell lines. PT-112 demonstrated cancer cell selectivity, inhibiting cell growth and leading to cell death in prostate cancer cells without affecting the non-tumorigenic epithelial prostate cell line RWPE-1 at the concentrations tested. PT-112 also caused caspase-3 activation, as well as stress features in mitochondria including ROS generation, compromised membrane integrity, altered respiration, and morphological changes. Moreover, PT-112 induced damage-associated molecular pattern (DAMP) release, the first demonstration of ICD in human cancer cell lines, in addition to autophagy initiation across the panel. Taken together, PT-112 caused selective stress, growth inhibition and death in human prostate cancer cell lines. Our data provide additional insight into mitochondrial stress and ICD in response to PT-112. PT-112 anticancer immunogenicity could have clinical applications and is currently under investigation in a Phase 2 mCRPC study.

Multidisciplinary and personalized approach to the management of mycosis fungoides with chlormethine gel: a collection of clinical experiences.

Topical chlormethine (CL) gel formulation was approved by the EMA in 2017 for the treatment of adult patients with mycosis fungoides (MF). To expand the knowledge on the management of MF, this paper provides an overview of clinical practice evidence about the MF diagnostic phase and a collection of clinical experiences to better characterize the use of CL gel in daily practice. Collected cases underline the importance of the concomitant biopsy and clinical evaluation in the diagnostic phase, with the contribution of a multidisciplinary team, and support the use of CL gel as a first-line or adjuvant treatment in selected patients.

Effect of Abelmoschus esculentus L. (Okra) on Dyslipidemia: Systematic Review and Meta-Analysis of Clinical Studies.

The global prevalence of cardiovascular diseases (CVDs), including dyslipidemia and atherosclerosis, is rising. While pharmacological treatments for dyslipidemia and associated CVDs exist, not all individuals can afford them, and those who do often experience adverse side effects. Preclinical studies have indicated the potential benefits of Abelmoschus esculentus and its active phytochemicals in addressing dyslipidemia in rodent models of diabetes. However, there is limited clinical evidence on lipid parameters. Thus, this study aimed to assess the potential impact of Abelmoschus esculentus on dyslipidemia. A literature search was performed on PubMed, Scopus, and Cochrane Library for relevant trials published from inception until 11 August 2024. Data analysis was performed using Jamovi software version 2.4.8 and Review Manager (version 5.4), with effect estimates reported as standardized mean differences (SMDs) and 95% confidence intervals (CI). The evidence from eight studies with nine treatment arms showed that Abelmoschus esculentus reduces total cholesterol (TC), SMD = -0.53 (95% CI: -1.00 to -0.07), p = 0.025), compared to placebo. Additionally, triglyceride (TG) was reduced in Abelmoschus esculentus compared to placebo, SMD = -0.24 (95% CI: -0.46 to -0.02), p = 0.035. Furthermore, low-density lipoprotein (LDL) was also reduced, SMD = -0.35 (95% CI: -0.59 to -0.11), p = 0.004 in Abelmoschus esculentus versus placebo. This remedy substantially increased high-density lipoprotein (HDL), SMD = 0.34 (95% CI: 0.07 to 0.61), p = 0.014). Abelmoschus esculentus substantially improved lipid profile in prediabetes, T2D, obesity, and diabetic nephropathy. While the evidence confirms the potential benefits of Abelmoschus esculentus in reducing dyslipidemia, it is important for future clinical studies to standardize the effective dosage for more reliable results. Therefore, future trials should focus on these markers in well-designed trials with sufficient sample sizes. Furthermore, Abelmoschus esculentus can be supplemented to the diet of the relevant populations to alleviate dyslipidemia.

The Potential Effects of Red Wine and Its Components on Neurocognitive Disorders: A Narrative Review.

The aging population is associated with a net increase in the incidence and prevalence of chronic-degenerative diseases, particularly neurocognitive disorders. Therefore, the identification of preventative strategies to restrain the burden of such chronic conditions is of key relevance. Red wine and its components have accumulated evidence regarding their positive effects in terms of neurological pathologies associated with neurocognitive symptoms. Based on this background, the present narrative review aims to summarize the state-of-the-art evidence on the effects of red wine and its components on neurocognitive disorders in both preclinical and clinical settings. The main findings highlight a protective effect of wine polyphenols present in red wine on dementia in different preclinical models of cognitive decline. The current translational clinical evidence remains uncertain, especially considering the risk-to-benefit ratio of alcohol consumption on brain health. Given the overall health risks associated with red wine consumption and consistent with the prevailing guidelines in the literature, there is insufficient evidence to support light-to-moderate red wine consumption as an effective strategy for preventing these diseases. However, the largely preclinical findings on polyphenols derived from red wine remain of significant interest in this context.

Qingxin Jieyu Granule alleviates myocardial infarction through inhibiting neutrophil extracellular traps via activating ANXA1/FPR2 axis

BackgroundMyocardial infarction (MI), representing the most severe manifestation of coronary artery disease (CAD), stands as a primary concern in the prevention and management of cardiovascular diseases. Clinical evidence demonstrates that Qingxin Jieyu Granule (QXJYG) is efficacious in treatment of MI patients. However, the mechanisms underlying its therapeutic effects remain to be elucidated. PurposeThis study aimed to evaluate the effects of QXJYG on MI and investigate its underlying mechanisms. Materials and methodsThe MI model in rats was developed through ligating the left anterior descending (LAD) artery. The effect of QXJYG on cardiac function impairment in MI rats was assessed by echocardiography, while the improvement of cardiomyocyte morphology and myocardial fibrosis after treatment with QXJYG was evaluated through hematoxylin-eosin (H&E) staining and Masson staining. The chemical constituents of QXJYG in blood were identified by using the UPLC-Q-TOF/MS technique. Furthermore, the molecular mechanism underlying the QXJYG therapeutic effect in MI was postulated based on the disease gene-drug target network analysis. Other technical methods such as ELISA, immunohistochemical staining, Western Blot analysis and application of pharmacological inhibitors were employed to verify the effectiveness of QXJYG in treating MI and explore its potential molecular targets. ResultsThe cardiac function in experimental rats post-MI was significantly impaired, as evidenced by an enlarged infarction area, disordered arrangement of cardiomyocytes, and aggravated myocardial fibrosis. QXJYG treatment significantly enhanced the cardiac function and reduced the pathological damage of the cardiac tissue in MI rats. Through the network pharmacology analysis, we identified that FPR2 might be a potential target of QXJYG in its cardiac protection role. QXJYG markedly downregulated the level of neutrophil extracellular traps (NETs) in MI rats, specifically manifested as a significant reduction in the Histone-DNA level and expression of myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) proteins. Furthermore, QXJYG upregulated the levels of ANXA1 and FPR2 proteins in MI rats. The level of FPR2 was markedly reduced in MI rats upon administration of WRW4, a specific inhibitor of FPR2, which was associated with exacerbated MI injury and an elevated level of NETs. When WRW4 was co-administered with QXJYG, the cardioprotective effects of QXJYG on MI were significantly diminished. However, the addition of DNase I did not result in significant changes of the outcomes in MI rats after QXJYG intervention. ConclusionQXJYG treatment alleviates cardiac tissue injury in MI rats by inhibiting NETs through activating the ANXA1/FPR2 axis. The findings extend our understanding of the therapeutic effectiveness of QXJYG and offer a scientific foundation for the clinical utilization of QXJYG.

Beyond low-density lipoprotein cholesterol levels: Impact of prior statin treatment on ischemic stroke outcomes

Although essential for cardiovascular therapy, the pleiotropic effects of statins on ischemic stroke lack clinical evidence. This study examined the effects of statins beyond low-density lipoprotein cholesterol (LDL-C) levels on mortality and stroke severity. A total of 825,874 patients with ischemic stroke were included in this study, of whom 125,650 statin users were 1:1 matched with non-users based on their LDL-C levels (±0.05mmol/L), forming the LDL-C-matched cohort. Associations between preceding statin treatment, in-hospital mortality, and stroke severity (National Institutes of Health Stroke Scale score ≥16) were estimated by multivariate and conditional logistic regression models in overall cohort and LDL-C-matched cohort, respectively. The overall statin effects reduced in-hospital mortality (odds ratio [OR]: 0.72, 95% confidence interval [CI]: 0.65-0.79, p<0.001) and moderate-to-severe stroke (OR: 0.93, 95% CI: 0.90-0.96, p<0.001). After matching for LDL-C levels, the reduction in mortality persisted (OR: 0.63, 95% CI: 0.52-0.77, p<0.001) but not for moderate-to-severe stroke (OR: 0.96, 95% CI: 0.90-1.02, p= 0.215). Stratified by LDL-C levels, the effects of statin beyond LDL-C in reducing mortality remained consistent across all LDL-C ranges but increased with LDL-C reduction for stroke severity and achieved statistical significance at LDL-C <2.60mmol/L. Mediation analyses showed that LDL-C reduction explained 0.35% (95% CI: 0.23-0.93, p= 0.235) of the statin treatment-mortality relationship and 12.47% (95% CI: 6.78-18.16, p<0.001) for moderate-to-severe stroke. When examining the overall statin efficacy, LDL-C <2.60mmol/L was not necessary for mortality reduction but for reducing stroke severity. The efficacy of statins in ischemic stroke outcomes is primarily derived from their effects beyond the LDL-C levels, suggesting that their neuroprotective effects should be considered in addition to their lipid-lowering effects.

Glycopyrrolate Premedication and Procedure-Related Events in Pediatric Upper Endoscopy.

Glycopyrrolate premedication is used for pediatric upper endoscopy procedures, with limited clinical evidence for efficacy. We investigated whether glycopyrrolate use is associated with lower incidence of procedure-related events and serious adverse events (SAEs) using the Pediatric Sedation Research Consortium registry. Pediatric upper endoscopy procedures performed between April 27, 2020 and February 3, 2022 were included (N = 1046). The primary outcome was the incidence of any procedure-related events during induction, maintenance, or recovery, and the secondary outcome was incidence of SAEs. The event rate was 15%, including 30 SAEs (3%). On multivariable analysis, glycopyrrolate was not associated with the overall event rate (odds ratio [OR]: 1.08; 95% confidence interval [CI]: 0.72, 1.61), but was associated with lower odds of SAEs (OR: 0.34; 95% CI: 0.13, 0.91). Although glycopyrrolate was associated with lower odds of SAEs after accounting for patient and procedure characteristics, validation through prospective trials is needed to support its routine use in clinical practice.

Pregnancy-related hormonal changes and thyroid growth: do they have an impact on the higher incidence of differentiated thyroid cancer in women?

To analyze whether pregnancy could play a role in the higher prevalence of differentiated thyroid carcinoma (DTC) in women. Estrogens strongly modify thyroid economy by increasing iodine clearance, thyroid hormone requirement and production. Human chorionic gonadotropin (hCG) contributes to the increased thyroid hormone synthesis. Both estrogens and hCG can interfere with the regulation of thyroid volume and with thyroid nodule development and progression. The potential effect of hCG is exclusively related to its weak agonistic activity on TSH receptor. Estrogen implication on normal and nodule-derived thyrocyte growth has been demonstrated in vitro and in animal models. Furthermore, there is solid clinical evidence showing a promoting effect of pregnancy on thyroid volume and nodule development. Two metanalysis, one including retrospective and another prospective observational studies, failed to show an association between pregnancy and DTC. A large pooled prospective analysis using multivariable-adjusted Cox proportional hazard models did not demonstrate an association between DTC and parity. Similarly, no association between PTC occurrence and parity was observed in a prospective cohort analysis by linkage to the statewide Surveillance, Epidemiology, and End Results (SEER). The presently available evidence does not support an involvement of pregnancy in DTC etiology.

Excess dietary sugar and its impact on periodontal inflammation: a narrative review.

Sugar is omnipresent in the current food environment and sugar consumption has drastically risen over the past century. Extensive evidence highlights the negative health consequences of consuming excess dietary sugars, leading the World Health Organization (WHO) and the American Heart Association (AHA) to devise guidelines to restrict sugar intake. According to the WHO's Global Oral Health Status Report of 2022, oral diseases and severe periodontitis are a massive public health problem, and dietary sugars are a modifiable risk factor. We conducted a literature review using key databases to summarise the health effects of excessive sugar consumption and their potential role in periodontal inflammation. Available evidence suggests that excess dietary fructose and sucrose can cause low-grade systemic inflammation; and induce dysbiosis in both gut and the oral microbiota. Also, dietary sugar is potentially addictive and hypercaloric and its overconsumption can lead to obesity, metabolic syndrome, and other risk factors for periodontal inflammation. Hence, an unbalanced diet with excess dietary sugars holds the potential to initiate and aggravate periodontal inflammation. In the modern food environment that enables and facilitates a high-sugar diet, adopting a diverse diet and restricting sugar intake according to WHO and AHA guidelines seem beneficial to systemic and periodontal health. Since clinical evidence is limited, future research should study the effectiveness of dietary interventions that control sugar consumption in preventing and managing the global public health problem of periodontal inflammation.

ESR Essentials: staging and restaging with FDG-PET/CT in oncology-practice recommendations by the European Society for Hybrid, Molecular and Translational Imaging.

Positron emission tomography (PET) stands as the paramount clinical molecular imaging modality, especially in oncology. Unlike conventional anatomical-morphological imaging methods such as computed tomography (CT) and magnetic resonance imaging (MRI), PET provides detailed visualizations of internal activity at the molecular and cellular levels. 18-fluorine-fluorodeoxyglucose ([18F]FDG)-PET combined with contrast-enhanced CT (ceCT) significantly improves the detection of various cancers. Appropriate patient selection is crucial, and physicians should carefully assess the appropriateness of [18F]FDG-PET/CT based on specific clinical criteria and evidence. Due to its high diagnostic accuracy, [18F]FDG-PET/CT is indispensable for evaluating the extent of disease, staging, and restaging known malignancies, and assessing the response to therapy. PET/CT imaging offers significant advantages in patient management, particularly by identifying occult metastases that might otherwise go undetected. This can help prevent unnecessary surgeries, allowing many patients to be redirected to systemic chemotherapy instead. However, it is important to note that the gold standard for surgical planning remains CT and/or MRI, depending on the body region. These imaging modalities, with or without associated angiography, provide superior contrast and spatial resolution, essential for detailed surgical preparation and planning. [18F]FDG-PET/CT has a central role in the precise and early diagnosis of cancer, contributing significantly to personalized treatment plans. However, it has limitations, including non-tumor-specific uptake and the potential to inaccurately capture the metabolic activity of certain tumor types due to low uptake in some well-differentiated tumor cell lines. Therefore, it should be utilized in clinical scenarios where it offers crucial diagnostic insights not readily available with other imaging modalities. KEY POINTS: Use [18F]FDG-PET/CT selectively based on clinical appropriateness criteria and existing evidence to optimize resource utilization and minimize patient exposure. Employ [18F]FDG-PET/CT in treatment planning and monitoring, particularly for assessing chemotherapy or radiotherapy response in FDG-avid lymphoma and solid tumors. When available, [18F]FDG-PET/CT can be integrated with other diagnostic tools, such as MRI, to enhance overall diagnostic accuracy.

Teaching of magnification in the undergraduate curriculum: A position statement from the British Endodontic Society Teachers of Endodontology Group.

This position statement on undergraduate teaching on the use of magnification in endodontics represents the consensus of the British Endodontic Society Teachers of Endodontology Group. Current clinical and scientific evidence, as well as the expertise of the committee, has been used to develop this statement. The contributors to this position statement consider, as a minimum requirement, the use of dental loupes in non-surgical endodontics at undergraduate level. It is recommended that the use of dental loupes should be integrated into endodontic clinical skills training and the performance of endodontic treatment in the undergraduate curriculum.

Effectiveness of Soleus Muscle Flap for The Coverage of Wound in Open Tibia Fracture in The Mid Shaft

Introduction: An open fracture of the tibia has been one of the most common long bone injuries. Soleus muscle flap supply can be a remedy for this kind of soft tissue difficulties. The soleus muscle flap’s blood supply may help in the construction of a longer, safer, and more functional flap. When the incision is clinically fit for covering, the flaps from the same leg are elevated between 0 and 14 days following the damage. In the majority of these cases, the flaps are covered with a split-thickness skin graft taken from the anterior aspect of the thigh in the same sitting. This can be a great solution. Aim of the study: The study aimed to assess the effectiveness of soleus muscle flap for the coverage of wound in open tibia fracture in the mid shaft. Methods: This prospective interventional study aimed to evaluate the outcomes of early coverage using the soleus muscle flap in the management of Gustilo type-IIIB fractures of the mid-shaft tibia. The study followed a quasi-experimental design and was conducted over an 18-month period from January 1, 2010, to June 30, 2011. The research took place in the Department of Orthopaedics and Traumatology at Dhaka Medical College Hospital (DMCH) and the National Institute of Traumatology and Orthopaedic Rehabilitation (NITOR) in Dhaka. The study population included all 15 patients admitted to the hospitals with clinical and radiological evidence of open Gustilo type-IIIB fractures of the mid-shaft tibia followed by the inclusion and exclusion criteria. Informed written consent was taken before data collection and confidentiality was maintained. The analysis was done by SPSS version 15. Result: Among 15 patients most (12) were male, 3 were female. Mean age was 38 ± 12 years. Majority were in 31-45 years. Male female ratio was 4:1. The selected study subjects were predominantly motor driver (26.66%), followed by day labor, housewife, service holder, farmer, and businessman (each was-13.33%), and student was 6.66%. ...

Eye movement desensitization and reprocessing (EMDR) therapy for the treatment of eating disorders: A systematic review of the literature

AbstractEye movement desensitization and reprocessing (EMDR) has demonstrated promise as a treatment for eating disorders (ED). The present study aimed to systematically evaluate the current evidence regarding the use of EMDR therapy in the treatment of EDs, ED symptomatology and body image concerns. Included articles were original studies that described the use of EMDR therapy in the treatment of EDs, published in the English language in a peer‐review journal. The search was conducted using four electronic databases: PsycINFO, MedLine, Embase, and Web of Science. Two independent reviewers conducted screening, selection, risk of bias assessment and data extraction. Of the initial search of 109 potential studies, eight met inclusion criteria, including six case studies, one quasi‐experimental study, and one randomised control trial (RCT). The RCT indicated that including an EMDR component did not have benefits over standard treatment for core ED symptoms, whereas the quasi‐experimental study demonstrated some benefits for inclusion of EMDR as a treatment adjunct for anorexia nervosa patients. Case studies indicated some promising outcomes for patients with various presentations. Despite EMDR being an available treatment for several decades now, there is limited clinical evidence regarding its efficacy in the treatment of EDs. These findings highlight a critical need for more clinical research in this area to ensure clinical practice is guided and supported by evidence‐based outcomes.

Combined Methylphenidate and Selective Serotonin Reuptake Inhibitors in Adults With Attention-Deficit/Hyperactivity Disorder.

Depression is a common comorbidity of adult attention-deficit/hyperactivity disorder (ADHD), and the combination of methylphenidate and selective serotonin reuptake inhibitors (SSRIs) is a frequently prescribed treatment. However, there is limited clinical evidence on the safety of this medication combination in adults with ADHD. To evaluate the safety of administering a combination of SSRI and methylphenidate in adults with ADHD and comorbid depression. This cohort study obtained data from a nationwide claims database in South Korea from January 2016 to February 2021. Participants were adults aged 18 years or older with a diagnosis of ADHD and depressive disorder who were prescribed methylphenidate. Comparisons of 4 groups who received prescriptions were conducted: (1) SSRI plus methylphenidate (hereafter, SSRI) group vs methylphenidate-only group and (2) methylphenidate plus fluoxetine (hereafter, fluoxetine) group vs methylphenidate plus escitalopram (hereafter, escitalopram) group (compared to find a preferable treatment option). Data analysis was conducted between July and December 2023. New users of the methylphenidate and SSRI combination among adults with both ADHD and depressive disorder. A total of 17 primary and secondary outcomes, including neuropsychiatric and other events, were assessed, with respiratory tract infection used as a control outcome. Groups were matched at a 1:1 ratio using a propensity score to balance confounders. A Cox proportional hazards regression model was used to calculate hazard ratio (HRs) and 95% CIs. Subgroup analysis by sex and sensitivity analyses in varying epidemiologic settings were conducted. The study included 17 234 adults with ADHD (mean [SD] age at study entry, 29.4 [10.8] years; 9079 females [52.7%]). There was no difference in the risk of outcomes between the methylphenidate-only and SSRI groups, except for a lower risk of headache in the SSRI group (HR, 0.50; 95% CI, 0.24-0.99). In sensitivity analyses of fluoxetine vs escitalopram, the risk of hypertension (HR: 1:n matching, 0.26; 95% CI, 0.08-0.67) and hyperlipidemia (HR: 1:n matching, 0.23; 95% CI, 0.04-0.81) was lower in the fluoxetine group than in the escitalopram group. Results of this study revealed no significant increase in adverse event risk associated with use of SSRI plus methylphenidate vs methylphenidate alone in adults with ADHD and comorbid depression. Instead, the combination was associated with a lower risk of headache.

Low-dose methadone added to another opioid for cancer pain: a multicentre prospective study

ContextThe use of methadone for cancer pain management is gaining wider acceptance. However, switching to methadone treatment can still pose challenges. Consequently, there is ongoing development of its use in low doses in combination with other opioids, despite a lack of clinical evidence regarding its efficacy and safety.ObjectivesThis study aimed to evaluate the efficacy and tolerability of low-dose methadone in combination with another opioid in patients with moderate-to-severe cancer-related pain in a clinical setting.Patients and methodsThis was a prospective, open-label study conducted in 19 pain and/or palliative care centres treating patients with cancer-related pain. Pain intensity, patients' global impression of change, and adverse effects were assessed on day 7 and day 14. The main outcome measure was the proportion of responders.ResultsThe study included 92 patients. The daily dose of methadone was 3 [3–6] mg at baseline, 9 [4–10] mg on day 7 and 10 [6–15] mg on day 14. The NRS pain ratings significantly decreased from 7 [6–8] at baseline to 5 [3–6] on visit 2 (p < .0001) and 4 [3–6] on visit 3 (p < .0001). Similarly, the VRS pain ratings decreased from 3 [3–3] at baseline to 2 [2–3] on visit 2 (p = 0.026) and 2 [1–3] (p < 0.001) on visit 3. At Visits 1 and 2, half of the patients were considered Responders. Of those responders, 73.5% were High-Responders at Visit 1 and 58.7% were High-Responders at Visit 2. No adverse events related to the risk of QT prolongation, overdose, or drug interactions were reported.ConclusionFor patients experiencing moderate to severe cancer-related pain despite initial opioid treatment, our study found that low-dose methadone, when used in combination with another opioid, was both safe and effective. This supports the use of methadone as an adjunct to opioid-based treatment for cancer pain.

Summary of Best Evidence for Perioperative Management Practices in Hair Transplantation Patients : Facial Skeleton.

To integrate and summarize the best evidence on perioperative management practices for hair transplantation patients, providing an evidence-based reference for clinical. An exhaustive literature search was conducted to identify the best evidence for managing patients undergoing hair transplantation during the perioperative period. The databases searched included Up To Date, BMJ Best Practice, UK National Institute for Health and Care Excellence, National Guideline Clearing House, Scottish Intercollegiate Guidelines Network, Guidelines International Network, Cochrane Library, JBI Database of Systematic Reviews and Implementation Reports, PubMed, Web of Science, European Dermatology Forum, China National Knowledge Infrastructure, Wanfang Data, Medlive Guideline Network, and Sinomed. The search spanned publications from February 2013 to February 2024, focusing on clinical decisions, evidence summaries, guidelines, and expert consensus. We finally identified 22 articles with high-quality results (consisting of 9 clinical decisions, 6 guidelines, 7 expert consensuses), providing 41 pieces of evidence across seven categories: assessment of transplantation conditions, transplant planning and preoperative preparation, anesthetic preparations, surgical methods and operation skills, postoperative wound management, medication-related guidance, optimization of nursing and treatment strategies. Special emphasis has been placed on the sections covering anesthesia preparation, surgical methods, and operational techniques, with detailed explanations provided. The summarized best evidence on perioperative management practices for hair transplantation patients can serve as evidence-based guidelines for clinical. It is recommended that clinical staff adopt evidence-based recommendations to improve and optimize patient outcomes and promote postoperative recovery. As these evidences came from different countries, factors such as the clinical environment should be evaluated before application. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

PET Imaging of the Serotonin 1A Receptor in Major Depressive Disorder: Hierarchical Multivariate Analysis of [11C]WAY100635 Overcomes Outcome Measure Discrepancies

Abstract The serotonin 1A receptor has been linked to both the pathophysiology of major depressive disorder (MDD) and the antidepressant action of serotonin reuptake inhibitors. Most PET studies of the serotonin 1A receptor in MDD used the receptor antagonist radioligand, [carbonyl-11C]WAY100635; however the interpretation of the combined results has been contentious owing to reports of higher or lower binding in MDD with different outcome measures. The reasons for these divergent results originate from several sources, including properties of the radiotracer itself, which complicate its quantification and interpretation; as well as from previously reported differences between MDD and healthy volunteers in both reference tissue binding and plasma free fraction, which are typically assumed not to differ. Recently, we have developed two novel hierarchical multivariate methods which we validated for the quantification and analysis of [11C]WAY100635, which show better accuracy and inferential efficiency compared to standard analysis approaches. Importantly, these new methods should theoretically be more resilient to many of the factors thought to have caused the discrepancies observed in previous studies. We sought to apply these methods in the largest [11C]WAY100635 sample to date, consisting of 160 individuals, including 103 MDD patients, of whom 50 were not-recently-medicated and 53 were antidepressant-exposed, as well as 57 healthy volunteers. While the outcome measure discrepancies were substantial using conventional univariate analysis, our multivariate analysis techniques instead yielded highly consistent results across PET outcome measures and across pharmacokinetic models, with all approaches showing higher serotonin 1A autoreceptor binding potential in the raphe nuclei of not-recently-medicated MDD patients relative to both healthy volunteers and antidepressant-exposed MDD patients. Moreover, with the additional precision of estimates afforded by this approach, we can show that while binding is also higher in projection areas in this group, these group differences are approximately half of those in the raphe nuclei, which are statistically distinguishable from one another. These results are consistent with the biological role of the serotonin 1A autoreceptor in the raphe nuclei in regulating serotonin neuron firing and release, and with preclinical and clinical evidence of deficient serotonin activity in MDD due to over expression of autoreceptors resulting from genetic and/or epigenetic effects. These results are also consistent with downregulation of autoreceptors as a mechanism of action of selective serotonin reuptake inhibitors. In summary, the results using multivariate analysis approaches therefore demonstrate both face and convergent validity, and may serve to provide a resolution and consensus interpretation for the disparate results of previous studies examining the serotonin 1A receptor in MDD.

Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes

Cancer treatment continues to be a substantial problem due to tumor complexities and persistence, demanding novel therapeutic techniques. This review investigates the synergistic potential of combining photodynamic therapy (PDT) and tailored medication delivery technologies to increase mitochondrial toxicity and improve cancer outcomes. PDT induces selective cellular damage and death by activating photosensitizers (PS) with certain wavelengths of light. However, PDT’s efficacy can be hampered by issues such as poor light penetration and a lack of selectivity. To overcome these challenges, targeted drug delivery systems have emerged as a promising technique for precisely delivering therapeutic medicines to tumor cells while avoiding off-target effects. We investigate how these technologies can improve mitochondrial targeting and damage, which is critical for causing cancer cell death. The combination method seeks to capitalize on the advantages of both modalities: selective PDT activation and specific targeted drug delivery. We review current preclinical and clinical evidence supporting the efficacy of this combination therapy, focusing on case studies and experimental models. This review also addresses issues such as safety, distribution efficiency, resistance mechanisms, and costs. The prospects of further research include advances in photodynamic agents and medication delivery technology, with a focus on personalized treatment. In conclusion, combining PDT with targeted drug delivery systems provides a promising frontier in cancer therapy, with the ability to overcome current treatment limits and open the way for more effective, personalized cancer treatments.