-
Drug Design, Development and Therapy 2024Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the... (Randomized Controlled Trial)
Randomized Controlled Trial
Preoperative Anxiolytic and Sedative Effects of Intranasal Remimazolam and Dexmedetomidine: A Randomized Controlled Clinical Study in Children Undergoing General Surgeries.
PURPOSE
Remimazolam, an ultra-short-acting and fast-metabolized sedative, has only been sporadically investigated in children. This study was performed to determine the beneficial effects of intranasal remimazolam or dexmedetomidine on preoperative anxiety in children undergoing general surgeries.
PATIENTS AND METHODS
Ninety children were randomly and equally assigned to Group R (intranasal remimazolam 1.5mg kg), Group D (intranasal dexmedetomidine 2 mcg kg), and Group C (intranasal distilled water). The primary outcomes were the preoperative anxiety scores using the modified Yale preoperative anxiety scale (m-Ypas). The secondary outcomes included the cooperation behaviour of intranasal drug application, preoperative sedation levels, parental separation anxiety scores (PSAS), and mask acceptance scores (MAS).
RESULTS
Group R showed a significant low anxiety at 10 min after intranasal premedication (vs group C, P=0.010; vs group D, P = 0.002) and at anaesthesia induction (vs group C, P = 0.004). Group D showed a significantly low anxiety score only prior to anaesthesia induction (vs group C, P = 0.005). Most children in group R achieved mild sedation at 10 min (vs group C, P < 0.001; vs group D, P < 0.001), with a few progressing to deep sedation afterwards, while group D tended toward deep sedation. Compared to Group C, patients in Group R performed significantly better on the MAS (P = 0.014) and PSAS (P = 0.008). However, remimazolam did cause poor cooperation behavior to the intranasal application due to its mucosal irritation (vs group C, P = 0.001; vs group D, P = 0.010).
CONCLUSION
Both intranasal remimazolam and dexmedetomidine can effectively alleviate preoperative anxiety in children. While intranasal remimazolam has a rapid onset, it produces only mild sedation and causes substantial nasal irritation.
TRIAL REGISTRATION
NCT04720963, January 22, 2021, ClinicalTrials.Gov.
Topics: Humans; Administration, Intranasal; Dexmedetomidine; Hypnotics and Sedatives; Male; Female; Anti-Anxiety Agents; Child; Child, Preschool; Anxiety; Benzodiazepines; Double-Blind Method
PubMed: 38774484
DOI: 10.2147/DDDT.S461122 -
Scientific Reports May 2024Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence... (Randomized Controlled Trial)
Randomized Controlled Trial
Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by disruptions in pain processing within the central nervous system. It exhibits a high prevalence among patients with a history of traumatic experiences, notably childhood sexual abuse (CSA). This study compared the efficacy of hyperbaric oxygen therapy (HBOT) to the current pharmacological standard of care for individuals suffering from CSA-related FMS. Forty-eight participants diagnosed with FMS and a history of CSA were randomly assigned to either the HBOT group (60 sessions of 100% oxygen at 2 ATA for 90 min, with air breaks every 5 min) or the medication (MED) group (FDA-approved medications, Pregabalin and Duloxetine). The primary endpoint was the Fibromyalgia impact questionnaire (FIQ) score, while secondary endpoints encompassed emotional status and daily functioning questionnaires, as well as pain thresholds and conditioned pain modulation tests. Brain activity was evaluated through single photon emission computed tomography (SPECT). Results revealed a significant group-by-time interaction for the FIQ score favoring HBOT over MED (p < 0.001), with a large effect size (Cohen's d = - 1.27). Similar findings were observed in emotional symptoms and functional measures. SPECT imaging demonstrated an increase in activity in pre-frontal and temporal brain areas, which correlated with symptoms improvement. In conclusion, HBOT exhibited superior benefits over medications in terms of physical, functional, and emotional improvements among FMS patients with a history of CSA. This associated with increased activity in pre-frontal and temporal brain areas, highlighting the neuroplasticity effect of HBOT.
Topics: Humans; Fibromyalgia; Hyperbaric Oxygenation; Female; Male; Adult; Middle Aged; Child Abuse, Sexual; Prospective Studies; Duloxetine Hydrochloride; Pregabalin; Treatment Outcome; Surveys and Questionnaires; Tomography, Emission-Computed, Single-Photon; Analgesics
PubMed: 38773296
DOI: 10.1038/s41598-024-62161-5 -
Journal of Feline Medicine and Surgery May 2024The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD).
OBJECTIVES
The aim of the present study was to assess the effect of gabapentin on blood pressure (BP) in cats with and without chronic kidney disease (CKD).
METHODS
A randomized, blinded, placebo-controlled crossover study was performed. A total of 29 cats were included: 13 cats with stable CKD (IRIS stage 2-4) and 16 apparently healthy cats (serum creatinine <1.6 mg/dl and urine specific gravity >1.035). The cats were evaluated twice, approximately 1 week apart, and BP (Doppler sphygmomanometry) was obtained 3 h after cats received either a single dose of gabapentin 10mg/kg PO or placebo. For each cat, BP readings were obtained at each visit using the same Doppler and sphygmomanometer unit, and the same cat holder and Doppler operator, in the same location.
RESULTS
After administration of a single dose of gabapentin (10 mg/kg PO), BP was significantly lower (median 122 mmHg, range 82-170) than after administration of the placebo (median 150 mmHg, range 102-191; = 0.001). In the CKD subgroup, BP was significantly lower after administration of gabapentin (median 129 mmHg, range 96-170) than after administration of the placebo (median 155 mmHg, range 102-191; = 0.008). In the healthy cat subgroup, BP was significantly lower after administration of gabapentin (median 121 mmHg, range 82-139) than after administration of the placebo (median 137 mmHg, range 102-177; = 0.002). The median change in BP was -12 mmHg (range -95 to 10) for healthy cats and -12 mmHg (range -43 to 21) for cats with CKD (no significant difference between subgroups).
CONCLUSIONS AND RELEVANCE
Gabapentin may decrease arterial BP in cats with and without CKD and these findings should be taken into account when gabapentin is administered to patients in which measurement of BP is needed.
Topics: Animals; Cats; Gabapentin; Cat Diseases; Renal Insufficiency, Chronic; Cross-Over Studies; Blood Pressure; Male; Female
PubMed: 38770706
DOI: 10.1177/1098612X241240326 -
Nature Communications May 2024Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor...
Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.
Topics: Tryptophan; Animals; Liver Neoplasms; Indoles; Humans; Proto-Oncogene Proteins c-myc; Mice; Carcinogenesis; Cell Line, Tumor; Kynurenine; Mice, Inbred C57BL; Liver; Male
PubMed: 38769298
DOI: 10.1038/s41467-024-47868-3 -
Scientific Reports May 2024Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in...
Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in addition to peripheral inflammatory symptoms. However, the pathogenesis of these psychiatric disorders remains mostly unknown. While prior research revealed that the Enterococcus faecalis 2001 (EF-2001) suppressed UC-like symptoms and accompanying depressive-like behaviors, observed in a UC model using dextran sulfate sodium (DSS), whether it has an anxiolytic effect remains unclear. Therefore, we examined whether EF-2001 attenuates DSS-induced anxiety-like behaviors. Treatment with 2% DSS for seven days induced UC-like symptoms and anxiety-like behavior through the hole-board test, increased serum lipopolysaccharide (LPS) and corticosterone concentration, and p-glucocorticoid receptor (GR) in the prefrontal cortex (PFC), and decreased N-methyl-D-aspartate receptor subunit (NR) 2A and NR2B expression levels in the PFC. Interestingly, these changes were reversed by EF-2001 administration. Further, EF-2001 administration enhanced CAMKII/CREB/BDNF-Drebrin pathways in the PFC of DSS-treated mice, and labeling of p-GR, p-CAMKII, and p-CREB showed colocalization with neurons. EF-2001 attenuated anxiety-like behavior by reducing serum LPS and corticosterone levels linked to the improvement of UC symptoms and by facilitating the CAMKII/CREB/BDNF-Drebrin pathways in the PFC. Our findings suggest a close relationship between UC and anxiety.
Topics: Animals; Enterococcus faecalis; Disease Models, Animal; Mice; Anti-Anxiety Agents; Dextran Sulfate; Male; Anxiety; Lipopolysaccharides; Corticosterone; Prefrontal Cortex; Colitis; Colitis, Ulcerative; Mice, Inbred C57BL
PubMed: 38769131
DOI: 10.1038/s41598-024-62309-3 -
BMC Pulmonary Medicine May 2024Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Remimazolam is safe and effective for moderate sedation during flexible bronchoscopy, but its safety and efficacy during endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) remains undetermined. The REST trial (NCT06275594) will be a prospective randomized study of remimazolam in patients undergoing EBUS-TBNA with conscious sedation. The primary aim is to evaluate whether remimazolam is safe and effective for moderate sedation during EBUS-TBNA compared to real-world midazolam and on-label midazolam.
METHODS
The REST trial will recruit 330 patients from four university hospitals with mediastinal lesions suspected of being lung cancer who are eligible for EBUS-TBNA under moderate sedation. The participants will be randomized into groups using remimazolam, real-world midazolam, and on-label midazolam (US prescribing information dosage) to perform EBUS-TBNA for procedural sedation. The primary endpoint will be procedural success using composite measures.
DISCUSSION
The REST trial will prospectively evaluate the efficacy and safety of remimazolam during EBUS-TBNA under moderate sedation. It will provide information for optimizing sedation modalities and contribute to practical benefits in patients undergoing EBUS-TBNA.
TRIAL REGISTRATION
ClinicalTrials.gov (NCT06275594). Prospectively registered on 15 February 2024.
Topics: Humans; Prospective Studies; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Conscious Sedation; Lung Neoplasms; Midazolam; Hypnotics and Sedatives; Benzodiazepines; Bronchoscopy; Male; Female; Randomized Controlled Trials as Topic; Adult; Middle Aged
PubMed: 38760702
DOI: 10.1186/s12890-024-03067-w -
BMC Primary Care May 2024In Australia, motor vehicle crashes (MVC)-related health data are available from insurance claims and hospitals but not from primary care settings. This study aimed to...
BACKGROUND
In Australia, motor vehicle crashes (MVC)-related health data are available from insurance claims and hospitals but not from primary care settings. This study aimed to identify the frequency of MVC-related consultations in Australian general practices, explore the pharmacological management of health conditions related to those crashes, and investigate general practitioners' (GPs) perceived barriers and enablers in managing these patients.
METHODS
Mixed-methods study. The quantitative component explored annual MVC-related consultation rates over seven years, the frequency of chronic pain, depression, anxiety or sleep issues after MVC, and management with opioids, antidepressants, anxiolytics or sedatives in a sample of 1,438,864 patients aged 16 + years attending 402 Australian general practices (MedicineInsight). Subsequently, we used content analysis of 81 GPs' qualitative responses to an online survey that included some of our quantitative findings to explore their experiences and attitudes to managing patients after MVC.
RESULTS
MVC-related consultation rates remained stable between 2012 and 2018 at around 9.0 per 10,000 consultations. In 2017/2018 compared to their peers, those experiencing a MVC had a higher frequency of chronic pain (48% vs. 26%), depression/anxiety (20% vs. 13%) and sleep issues (7% vs. 4%). In general, medications were prescribed more after MVC. Opioid prescribing was much higher among patients after MVC than their peers, whether they consulted for chronic pain (23.8% 95%CI 21.6;26.0 vs. 15.2%, 95%CI 14.5;15.8 in 2017/2018, respectively) or not (15.8%, 95%CI 13.9;17.6 vs. 6.7%, 95% CI 6.4;7.0 in 2017/2018). Qualitative analyses identified a lack of guidelines, local referral pathways and decision frameworks as critical barriers for GPs to manage patients after MVC. GPs also expressed interest in having better access to management tools for specific MVC-related consequences (e.g., whiplash/seatbelt injuries, acute/chronic pain management, mental health issues).
CONCLUSION
Chronic pain, mental health issues and the prescription of opioids were more frequent among patients experiencing MVC. This reinforces the relevance of appropriate management to limit the physical and psychological impact of MVC. GPs identified a lack of available resources (e.g. education, checklists and management support tools) for managing MVC-related consequences, and the need for local referral pathways and specific guidelines to escalate treatments.
Topics: Humans; Australia; Accidents, Traffic; Female; Male; General Practice; Adult; Middle Aged; Chronic Pain; Analgesics, Opioid; Adolescent; Psychological Trauma; Young Adult; Anxiety; Sleep Wake Disorders; Depression; Aged; Hypnotics and Sedatives; Practice Patterns, Physicians'; Antidepressive Agents; General Practitioners; Anti-Anxiety Agents
PubMed: 38755534
DOI: 10.1186/s12875-024-02421-5 -
PloS One 2024Recently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Recently, several randomized controlled trials (RCTs) of fluvoxamine have been successfully conducted for the treatment of patients with coronavirus disease 2019 (COVID-19). This systematic review and meta-analysis was to evaluate the efficacy and safety of fluvoxamine in patients with COVID-19.
METHODS
MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov were searched for RCTs which were performed to evaluate fluvoxamine and placebo up to January 31, 2024. Review Manager 5.3 was used to perform meta-analysis. The risk ratio (RR) and mean difference (MD) was analyzed and calculated with a random effect model.
RESULTS
We pooled 4,711 participants from six RCTs (2,382 in the fluvoxamine group and 2,329 in the placebo group). Compared to the placebo group, the fluvoxamine group had a significantly lower rate of clinical deterioration (RR, 0.73; P = 0.004; 95% CI, 0.59 to 0.90; I2 = 0%) and hospitalization (RR, 0.76; P = 0.04; 95% CI, 0.59 to 0.99; I2 = 0%). In the meantime, compared with the placebo group, fluvoxamine group did not show any higher risk of AEs (P = 0.13 and 0.91, respectively) in safety outcomes analysis. The subgroup analysis showed that fluvoxamine treatment performed more than 200 mg daily appears to be more effective than those performed less than 200 mg daily in reducing clinical deterioration and hospitalization risks, while not exhibiting higher AE and SAE risks than placebo group.
CONCLUSION
Fluvoxamine for patients with COVID-19, especially those who take 200 mg or more daily, is superior to the placebo group in reducing clinical deterioration and hospitalization, and did not show any higher risk of AEs and SAEs in safety concerns, which might be a promising intervention for COVID-19.
Topics: Fluvoxamine; Humans; COVID-19 Drug Treatment; Randomized Controlled Trials as Topic; SARS-CoV-2; COVID-19; Treatment Outcome; Hospitalization
PubMed: 38753761
DOI: 10.1371/journal.pone.0300512 -
Acta Dermato-venereologica May 2024Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding...
Pruritus in the elderly, particularly those cases without skin dryness or other identifiable causes, makes treatment challenging due to the lack of evidence regarding the therapeutic effects of antipruritics. This study proposes an age-related alloknesis mouse model for an evaluation system for such cases, and aimed to investigate the effectiveness and mechanisms of action of several drugs commonly used as antipruritics in Japan, utilizing this model. Mice 69-80 weeks old were used as aged mice, and the level of mechanical alloknesis was counted as the number of scratching behaviours in response to innocuous stimuli. Bepotastine, neurotropin, pregabalin, baricitinib, and abrocitinib were used as antipruritics, and yohimbine and methysergide as inhibitors of the descending inhibitory pathway. The findings suggest that mechanical alloknesis in aged mice is a suitable animal model for assessing pruritus in the elderly without xerosis, and pregabalin, neurotropin, baricitinib, and abrocitinib may be effective antipruritics in the elderly through activating both the noradrenergic and serotonergic descending inhibitory pathways. These findings may be useful for the selection of antipruritics for pruritus in the elderly without skin lesions or dryness.
Topics: Animals; Pruritus; Disease Models, Animal; Antipruritics; Chronic Disease; Behavior, Animal; Mice; Age Factors; Male; Sulfonamides; Pregabalin; Pyrazoles; Purines; Aging; Azetidines
PubMed: 38751178
DOI: 10.2340/actadv.v104.39950 -
Scientific Reports May 2024Current treatments for anxiety and depression show limited efficacy in many patients, indicating the need for further research into the underlying mechanisms. JNK1 has...
Current treatments for anxiety and depression show limited efficacy in many patients, indicating the need for further research into the underlying mechanisms. JNK1 has been shown to regulate anxiety- and depressive-like behaviours in mice, however the effectors downstream of JNK1 are not known. Here we compare the phosphoproteomes from wild-type and Jnk1-/- mouse brains and identify JNK1-regulated signalling hubs. We next employ a zebrafish (Danio rerio) larvae behavioural assay to identify an antidepressant- and anxiolytic-like (AA) phenotype based on 2759 measured stereotypic responses to clinically proven antidepressant and anxiolytic (AA) drugs. Employing machine learning, we classify an AA phenotype from extracted features measured during and after a startle battery in fish exposed to AA drugs. Using this classifier, we demonstrate that structurally independent JNK inhibitors replicate the AA phenotype with high accuracy, consistent with findings in mice. Furthermore, pharmacological targeting of JNK1-regulated signalling hubs identifies AKT, GSK-3, 14-3-3 ζ/ε and PKCε as downstream hubs that phenocopy clinically proven AA drugs. This study identifies AKT and related signalling molecules as mediators of JNK1-regulated antidepressant- and anxiolytic-like behaviours. Moreover, the assay shows promise for early phase screening of compounds with anti-stress-axis properties and for mode of action analysis.
Topics: Animals; Zebrafish; Anxiety; Mitogen-Activated Protein Kinase 8; Larva; Mice; Signal Transduction; Behavior, Animal; Anti-Anxiety Agents; Phenotype; Antidepressive Agents; Disease Models, Animal; Brain; Proto-Oncogene Proteins c-akt
PubMed: 38750129
DOI: 10.1038/s41598-024-61337-3