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Scientific Reports Jun 2024Intense exercise leads to increased production of free radicals, resulting in an inflammatory response in athletes. For this reason, it was decided to investigate...
Intense exercise leads to increased production of free radicals, resulting in an inflammatory response in athletes. For this reason, it was decided to investigate whether a single intensive exercise until exhaustion applied after a 2-week rest period would result in a violation of the pro-oxidant-antioxidant balance. Twenty-seven trained female basketball players (age: 16.55 ± 0.96 years, body mass: 66.40 ± 13.68 kg, height: 173.45 ± 5.14 cm) were enrolled to the study following the application of inclusion and exclusion criteria. Study was conducted at the end of the competitive training phase. Participants underwent incremental treadmill exercise, with blood samples collected before the test, immediately post-exercise, and after a 3-h restitution period. Total antioxidant capacity (TAC) levels increased significantly after exercise and remained unchanged after 3 h. Concentration of interleukin-10 (IL-10) and creatine kinase (CK) significantly increased after exercise and then decreased. Concentration of interleukin-2 (IL-2) was significantly reduced immediately and 3 h after exercise, while interleukin-13 (IL-13), interleukin-1α (IL-1α), and tryptophan (TRP) decreased 3 h after exercise. No significant changes were observed in other biochemical parameters. Obtained results show an increased antioxidant capacity which reduced oxidative stress and inflammation in response to intense exercise indicating that rested athletes have a high adaptation and elevated tolerance to effort.
Topics: Humans; Female; Oxidative Stress; Basketball; Inflammation; Adolescent; Antioxidants; Interleukin-10; Athletes; Creatine Kinase; Rest; Interleukin-1alpha; Interleukin-2; Exercise; Interleukin-13; Tryptophan
PubMed: 38918542
DOI: 10.1038/s41598-024-65309-5 -
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 -
Acta Dermato-venereologica Jun 2024This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine... (Comparative Study)
Comparative Study
This retrospective study investigates the efficacy of 2 treatment regimens, pregabalin alone versus pregabalin combined with ketamine, amitriptyline, and lidocaine cream, in reducing itch in patients with brachioradial pruritus at a tertiary care center. Electronic medical records of 64 brachioradial pruritus patients seen at the University of Miami Itch Center were analyzed. A significant reduction in itch scores was seen with both treatments, with no significant difference between the groups. A small number of patients experienced adverse effects, including drowsiness and weight gain with pregabalin and skin irritation with ketamine, amitriptyline, and lidocaine cream. Ultimately, our findings underscore the potential of utilizing combined therapy for difficult-to-treat brachioradial pruritus cases and implementing individualized approaches for managing neuropathic pruritus. Further controlled clinical trials are needed to establish optimal treatment protocols.
Topics: Humans; Retrospective Studies; Pruritus; Female; Male; Tertiary Care Centers; Middle Aged; Treatment Outcome; Amitriptyline; Lidocaine; Ketamine; Pregabalin; Aged; Drug Therapy, Combination; Adult; Antipruritics; Florida; Skin Cream; Administration, Cutaneous; Electronic Health Records
PubMed: 38916180
DOI: 10.2340/actadv.v104.40246 -
Frontiers in Cellular Neuroscience 2024
PubMed: 38915874
DOI: 10.3389/fncel.2024.1440772 -
Systematic Reviews Jun 2024Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a...
BACKGROUND
Non-invasive brain stimulation (NIBS) is a promising intervention for treatment-resistant schizophrenia. However, there are multiple available techniques and a comprehensive synthesis of evidence is lacking. Thus, we will conduct a systematic review and network meta-analysis to investigate the comparative efficacy and safety of NIBS techniques as an add-on to antipsychotics for treatment-resistant schizophrenia.
METHODS
We will include single- and double-blind randomized-controlled trials (RCT) comparing any NIBS technique with each other or with a control intervention as an add-on to antipsychotics in adult patients with treatment-resistant schizophrenia. We will exclude studies focusing on predominant negative symptoms, maintenance treatment, and single sessions. The primary outcome will be a change in overall symptoms, and secondary outcomes will be a change in symptom domains, cognitive performance, quality of life, functioning, response, dropouts, and side effects. We will search for eligible studies in previous reviews, multiple electronic databases and clinical trial registries from inception onwards. At least two independent reviewers will perform the study selection, data extraction, and risk of bias assessment. We will measure the treatment differences using standardized mean difference (SMD) and odds ratio (OR) for continuous and dichotomous outcomes, respectively. We will conduct pairwise and network meta-analysis within a frequentist framework using a random-effects model, except for rare event outcomes where we will use a fixed-effects Mantel-Haenszel method. We will investigate potential sources of heterogeneity in subgroup analyses. Reporting bias will be assessed with funnel plots and the Risk of Bias due to Missing Evidence in Network meta-analysis (ROB-MEN) tool. The certainty in the evidence will be evaluated using the Confidence in Network Meta-analysis (CINeMA) approach.
DISCUSSION
Our network meta-analysis would provide an up-to-date synthesis of the evidence from all available RCTs on the comparative efficacy and safety of NIBS for treatment-resistant schizophrenia. This information could guide evidence-based clinical practice and improve the outcomes of patients.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42023410645.
Topics: Humans; Systematic Reviews as Topic; Network Meta-Analysis; Schizophrenia, Treatment-Resistant; Transcranial Direct Current Stimulation; Antipsychotic Agents; Transcranial Magnetic Stimulation; Meta-Analysis as Topic; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 38915121
DOI: 10.1186/s13643-024-02585-2 -
Dermatology and Therapy Jun 2024Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently... (Review)
Review
Chronic pruritus (CP) is defined as an unpleasant sensation causing a desire to scratch and lasting > 6 weeks. It has a multifactorial etiology but is more frequently associated with chronic inflammatory dermatoses and systemic disorders. Psychogenic pruritus and neurological disorders are other less common etiologies, while, in some patients, it is idiopathic. CP appears to be processed by non-histaminergic pathway, contributing to its complexity and therapeutic challenge. Moreover, regardless of the etiology, it is multidimensional, including cognitive, motivational and affective components. There is a close link between psychological distress and pruritus, with particular clinical expression in chronic inflammatory dermatoses, involving the activation of the hypothalamic-pituitary-adrenal axis (and its cutaneous equivalent), the sympathetic nervous system, the release of hormones and peptides, the role of immune cells (T and B cells, macrophages) and immune-related cells in the skin (mast cells, dendritic cells and keratinocytes). Moreover, there is strong evidence that psychological factors influence the experience of pruritus. CP can also cause psychiatric disorders, including but not limited to anxiety and depression, and also lead to significant quality of life (QoL) impairment. Thereby, although a psychodermatological assessment should ideally be carried out in the context of a specific psychodermatology consultation, a brief mental health assessment could be part of the general dermatological approach to these patients. Considering that mental health, QoL and pruritus are closely linked, psychotherapeutic interventions and/or psychotropic drugs should thus be considered in some patients as an adjunct to the pharmacological treatment of CP.
PubMed: 38914907
DOI: 10.1007/s13555-024-01214-z -
Scientific Reports Jun 2024Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the...
Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.
Topics: Gastrointestinal Microbiome; N-Methyl-3,4-methylenedioxyamphetamine; Animals; Rats; Male; Hyperthermia; Bile Acids and Salts; Anti-Bacterial Agents; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Deoxycholic Acid
PubMed: 38914648
DOI: 10.1038/s41598-024-65433-2 -
JAMA Network Open Jun 2024There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration.
OBJECTIVE
To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone.
DESIGN, SETTING, AND PARTICIPANTS
In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented.
INTERVENTIONS
Internet and telephone self-management support, codesigned and coproduced with patients and practitioners.
MAIN OUTCOMES AND MEASURES
The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis.
RESULTS
Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events.
CONCLUSIONS AND RELEVANCE
In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue.
TRIAL REGISTRATION
ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).
Topics: Humans; Female; Male; Antidepressive Agents; Middle Aged; Telephone; Adult; Internet; Depression; United Kingdom
PubMed: 38913372
DOI: 10.1001/jamanetworkopen.2024.18383 -
Bundesgesundheitsblatt,... Jun 2024Many diseases are accompanied by symptoms that can impair the ability to perform complex everyday tasks, such as active participation in road traffic. If a cure is not... (Review)
Review
Many diseases are accompanied by symptoms that can impair the ability to perform complex everyday tasks, such as active participation in road traffic. If a cure is not possible, the aim of drug therapy is to alleviate the symptoms to such an extent that the patient no longer has any restrictions in everyday life. However, around 20% of the approximately 100,000 medicines licensed in Germany have traffic-relevant side effects that can also lead to driving impairment.It is assumed that the effect of a drug is at least partially responsible for one in four traffic accidents and that one in ten victims of fatal road accidents has taken psychotropic drugs before driving. In addition to alcohol and drugs, medications from the benzodiazepine, opioid, and antidepressant groups are suspected of impairing driving safety in particular. The effects of these substances on young people have been described many times, but this review deals specifically with the traffic-relevant (side) effects of various classes of drugs on elderly people (aged 65 and over).Older people in particular often have to take different medications, which are metabolized differently compared to younger people due to underlying diseases and can also interact with each other. It was found that (1) older people often react more sensitively to substances, (2) not all representatives of a drug class have the same effect on driving safety, and (3) a general assessment of a drug's safety is not possible, since the effects also depend on other factors such as underlying diseases, treatment regimen, and the time of day the medication is taken.
PubMed: 38913167
DOI: 10.1007/s00103-024-03913-6 -
Rivista Di Psichiatria 2024To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To investigate the effects of electroacupuncture combined with paliperidone palmitate long-acting injection (PP-LAI) on withdrawal symptoms and neurotransmitters in methamphetamine (MA) addicts.
MATERIALS AND METHODS
A total of 109 methamphetamine addicts, who were treated in the hospital from October 2021 to October 2022, were selected. According to the random number table, the patients were divided into the study group (n=54) and the control group (n=55), in which the control group was treated with PP-LAI and the study group was treated with electroacupuncture on the basis of the control group; the methamphetamine withdrawal symptom score scale was used to assess the therapeutic effect before treatment and within 12 months after treatment; the changes of brain neurotransmitters dopamine, γ-aminobutyric acid, serotonin, acetylcholine values were compared between the two groups.
RESULTS
1) There was no statistical difference in MA withdrawal symptom scores between the two groups before treatment (p>0.05); 2) MA withdrawal symptom scores have a statistically significant difference between the study group and the control group after 3 and 6 months of treatment; 3) dopamine levels in the study group were significantly higher than those in the control group after 6 months of completion of treatment, and γ-aminobutyric acid values and 5- serotonin values in the study group were significantly lower than those in the control group (p<0.05).
CONCLUSIONS
Electroacupuncture combined with PP-LAI can partially improve the withdrawal symptoms and anxiety of methamphetamine addicts. This is a potential treatment for preventing relapse of withdrawal symptoms.
Topics: Humans; Paliperidone Palmitate; Substance Withdrawal Syndrome; Methamphetamine; Male; Adult; Electroacupuncture; Amphetamine-Related Disorders; Female; Neurotransmitter Agents; Combined Modality Therapy; Delayed-Action Preparations; Dopamine; Serotonin; gamma-Aminobutyric Acid; Middle Aged; Treatment Outcome; Antipsychotic Agents
PubMed: 38912759
DOI: 10.1708/4288.42698