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Introduction: during laparoscopic surgery, carbon dioxide (CO2) insufflation to create pneumoperitoneum increases blood pressure, heart rate and systemic vascular resistance. The purpose of our study was to investigate the efficacy of magnesium sulfate in preventing adverse hemodynamic reactions associated with pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. Methods: we conducted a prospective, randomized, double-blind, controlled clinical study of patients scheduled for laparoscopic cholecystectomy and divided into two equal groups: the Mg2+ group received slow intravenous magnesium sulfate 50 mg/kg injection prior to pneumoperitoneum insufflation while the S group received the same volume of 0.9 % saline. Our primary endpoint was intraoperative changes in systolic blood pressure (SBP) related to pneumoperitoneum, in particular at 1 minute after insufflation. The secondary endpoints were the haemodynamic effects of pneumoperitoneum in terms of systolic blood pressure (SP), diastolic blood pressure (DP), mean arterial pressure (MAP) and heart rate (HR) from 2 minutes after insufflation to extubation and postoperatively, and the presence of possible adverse reactions related to the administration of magnesium sulphate. Results: we included 70 patients divided into two groups of 35. SP was significantly higher in the S group at insufflation (T0), 3 min, 4 min and 5 min post-operative, and at 60 min after surgery. HR was significantly higher in patients in the S group compared to the Mg2+ group at 7 min and 8 min after insufflation. No significant differences in DP and MAP measurements were observed between the 2 groups. No adverse reactions related to magnesium administration were reported. Conclusion: magnesium sulfate administered prior to pneumoperitoneum insufflation provided improved intraoperative hemodynamic stability during laparoscopic surgery.
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Presión Sanguínea , Colecistectomía Laparoscópica , Frecuencia Cardíaca , Hemodinámica , Sulfato de Magnesio , Neumoperitoneo Artificial , Humanos , Sulfato de Magnesio/administración & dosificación , Sulfato de Magnesio/farmacología , Estudios Prospectivos , Femenino , Masculino , Método Doble Ciego , Colecistectomía Laparoscópica/métodos , Colecistectomía Laparoscópica/efectos adversos , Neumoperitoneo Artificial/efectos adversos , Neumoperitoneo Artificial/métodos , Hemodinámica/efectos de los fármacos , Persona de Mediana Edad , Adulto , Presión Sanguínea/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Dióxido de Carbono/administración & dosificación , Adulto Joven , Insuflación/métodosRESUMEN
INTRODUCTION: The popular traditional Chinese medicine (TCM) compound FYTF-919 (Zhong Feng Xing Nao prescription) may improve outcome from acute intracerebral hemorrhage (ICH) through effects on brain edema, hematoma absorption, and the immune system. This study is to assess whether FYTF-919 is safe and effective as compared to matching placebo treatment in patients with acute ICH. METHODS: The ongoing Chinese Herbal medicine in patients with Acute INtracerebral hemorrhage (CHAIN) is a multicenter, prospective, randomized, double-blind placebo-controlled trial of FYTF-919 in patients with acute ICH at 20-30 hospital sites in China. Eligible ICH patients presenting within 48 h after symptom onset are randomly allocated to receive either FYTF-919 (100 mL per day × 28 d, oral) or matching placebo. A sample size of 1,504 patients is estimated to provide 90% power (α 0.05) to detect a ≥20% improvement in average utility-weight scores on the modified Rankin scale (UW-mRS) assessed at 90 days, with 6% non-adherence and 10% lost to follow-up. The primary efficacy outcome is UW-mRS at 90 days. Secondary outcomes include binary measures of the mRS, neurological impairment on the National Institute of Health Stroke Scale, and health-related quality of life on the EuroQol EQ-5D-5L scale at different time points over 6 months of follow-up. The key safety measure is serious adverse events. CONCLUSION: CHAIN is on schedule to provide reliable evidence over the benefits of a popular herbal TCM for the treatment of acute ICH.
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Hemorragia Cerebral , Medicamentos Herbarios Chinos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Método Doble Ciego , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Hemorragia Cerebral/tratamiento farmacológico , Resultado del Tratamiento , Estudios Prospectivos , China , Factores de Tiempo , Recuperación de la Función , Estudios Multicéntricos como Asunto , Masculino , Femenino , Persona de Mediana Edad , Anciano , Enfermedad Aguda , Evaluación de la Discapacidad , Estado Funcional , AdultoRESUMEN
BACKGROUND: To compare the efficacy and safety of ciprofol, propofol, propofol and etomidate mixture or ciprofol and etomidate mixture in patients undergoing painless gastroscopic anesthesia, and to explore the optimal plan to relieve the patient's discomfort. METHODS: A total of 120 patients scheduled for painless gastroscopy were randomly assigned to 4 groups: propofol (Group P), ciprofol (Group C), propofol-etomidate mixture (Group P-E), and ciprofol-etomidate mixture (Group C-E). The success rate of gastroscopy examination, patient satisfaction, incidence of injection pain, hemodynamic parameters, induction time, procedure time, the consumption of drugs, awakening time, and incidence of adverse events were evaluated. RESULTS: All patients in the study successfully completed the gastroscopy. The satisfaction of patients in Group C-E was significantly higher than that in Group P (Pâ <â .05), but there was no statistical significance in the patient satisfaction among the other groups. Compared with Group P, the incidence of injection pain in Groups C and C-E significantly decreased (Pâ <â .05). There were no significant differences in the SBP, diastolic blood pressure, HR, and SpO2 among the 4 groups (Pâ >â .05). The awakening time of Group C was significantly longer than that of Groups P and P-E (Pâ <â .05), but there was no statistically significant difference in the awakening time of other groups. CONCLUSION: Ciprofol demonstrated efficacy in inducing sedation or anesthesia during painless gastroscopy that was similar to propofol, while exhibiting a comparable safety profile. Moreover, the combination of propofol and etomidate, as well as the combination of ciprofol and etomidate, were both shown to be equally safe and effective for this clinical application. These findings suggest that ciprofol can be considered as a safe and effective alternative for painless gastroscopy, and the ciprofol-etomidate mixture may be a better choice.
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Anestésicos Intravenosos , Etomidato , Gastroscopía , Propofol , Humanos , Propofol/efectos adversos , Propofol/administración & dosificación , Masculino , Método Doble Ciego , Femenino , Etomidato/efectos adversos , Etomidato/administración & dosificación , Gastroscopía/métodos , Adulto , Persona de Mediana Edad , Anestésicos Intravenosos/efectos adversos , Anestésicos Intravenosos/administración & dosificación , Satisfacción del Paciente , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/administración & dosificación , Resultado del TratamientoRESUMEN
BACKGROUND: Local anesthetics are used in various sites and mechanisms to maximize perioperative analgesia and reduce opioid use and side effects. Pain management in the bariatric setting is challenging and the efficacy of local anesthetics intraoperatively is under current evaluation. OBJECTIVES: To determine the safety and efficacy of a new intra-abdominal anesthetic technique performed during laparoscopic bariatric operations: visceral block. METHODS: During this prospective randomized double-blinded pilot study, 16 patients undergoing bariatric surgery were treated with the injection of ropivacaine to the anterior esophagogastric junction fat, and 15 were injected with saline as control. RESULTS: The procedure was shown to be safe, and no adverse events nor side effects were encountered. A non-statistically significant trend toward the use of a non-opioid analgesia was documented during the first postoperative hours. CONCLUSIONS: Visceral block is a safe and feasible intraoperative procedure. A trend toward its efficacy warrants future larger scale studies.
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Anestésicos Locales , Cirugía Bariátrica , Laparoscopía , Dolor Postoperatorio , Ropivacaína , Humanos , Método Doble Ciego , Cirugía Bariátrica/métodos , Cirugía Bariátrica/efectos adversos , Proyectos Piloto , Femenino , Masculino , Anestésicos Locales/administración & dosificación , Ropivacaína/administración & dosificación , Adulto , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/etiología , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos , Laparoscopía/métodos , Bloqueo Nervioso/métodos , Resultado del Tratamiento , Obesidad Mórbida/cirugíaRESUMEN
Motor imagery (MI) is the mental representation of a movement without its execution. It activates internal representations of the movement without external stimulus through different memory-related processes. Although acute stress is frequent in the population and affects supraspinal structures essential for memory functionality, it is still unknown how that stress affects MI capacity and temporal congruence (TC) between execution and movement imagination. This study aimed to discover how acute stress may influence MI capacity and TC in the subscales of internal and external visual imagery and kinesthetic imagery. A double-blind, randomized trial was conducted. Sixty-two young, healthy subjects (mean age = 20.65 [2.54]; 39 females and 23 males) unfamiliar with the assessment and uses of MI were recruited. Participants were assigned by stratified randomization to the stress group or the control group. Stress was induced by the Maastricht Acute Stress Test (MAST), while the control group performed the MAST control protocol. MI capacity and TC were assessed before (t1) and after (t2) MAST stress or control using the Movement Imagery Questionnaire-3 (MIQ-3). Electrodermal activity and heart rate variability were further recorded as control variables to assess stress induction. Thirty subjects in the stress group and 26 subjects in the control group were analyzed. No significant group differences were observed when comparing MI capacity or TC in any subscales. These findings suggest that acute stress does not significantly affect MI capacity or TC in young, healthy, non-experienced MI subjects. MI could thus be a relevant helpful technique in stressful situations.
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Frecuencia Cardíaca , Imaginación , Estrés Psicológico , Humanos , Femenino , Masculino , Adulto Joven , Método Doble Ciego , Imaginación/fisiología , Frecuencia Cardíaca/fisiología , Movimiento/fisiología , Respuesta Galvánica de la Piel/fisiología , Adulto , Adolescente , Cinestesia/fisiología , Encuestas y CuestionariosRESUMEN
BACKGROUND: Algae-derived nutraceuticals, such as spirulina, have been reported to have biological activities that may minimize clinical consequences to COVID-19 infections. OBJECTIVES: This study aimed to determine whether spirulina is an effective treatment for high-risk patients with early COVID-19 in an outpatient setting. METHODS: The TOGETHER trial is a placebo-controlled, randomized, platform trial conducted in Brazil. Eligible participants were symptomatic adults with a positive rapid test for SARS-CoV-2 older than 50 y or with a known risk factor for disease severity. Patients were randomly assigned to receive placebo or spirulina (1 g twice daily for 14 d). The primary end point was hospitalization defined as either retention in a COVID-19 emergency setting for >6 h or transfer to tertiary hospital owing to COVID-19 at 28 d. Secondary outcomes included time-to-hospitalization, mortality, and adverse drug reactions. We used a Bayesian framework to compare spirulina with placebo. RESULTS: We recruited 1126 participants, 569 randomly assigned to spirulina and 557 to placebo. The median age was 49.0 y, and 65.3% were female. The primary outcome occurred in 11.2% in the spirulina group and 8.1% in the placebo group (odds ratio [OR]: 1.24; 95% credible interval: 0.84, 1.86). There were no differences in emergency department visit (OR: 1.21; 95% credible interval: 0.81, 1.83), nor time to symptom relief (hazard ratio: 0.90; 95% credible interval: 0.79, 1.03). Spirulina also not demonstrate important treatment effects in the prespecified subgroups defined by age, sex, BMI, days since symptom onset, or vaccination status. CONCLUSIONS: Spirulina has no any clinical benefits as an outpatient therapy for COVID-19 compared with placebo with respect to reducing the retention in an emergency setting or COVID-19-related hospitalization. There are no differences between spirulina and placebo for other secondary outcomes. This trial was registered at clinicaltrials.gov as NCT04727424.
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Tratamiento Farmacológico de COVID-19 , COVID-19 , Suplementos Dietéticos , Hospitalización , SARS-CoV-2 , Spirulina , Humanos , Masculino , Femenino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Anciano , Brasil , Método Doble Ciego , Resultado del TratamientoRESUMEN
BACKGROUND: It is unknown whether clinical benefit of proprotein convertase subtilisin/kexin type 9 inhibitors is associated with baseline or on-treatment triglyceride concentrations. OBJECTIVES: This study sought to examine relations between triglyceride levels and the effect of alirocumab vs placebo on cardiovascular outcomes using prespecified and post hoc analyses of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial. METHODS: Patients with recent acute coronary syndrome (ACS) (n = 18,924) and elevated atherogenic lipoproteins despite optimized statin therapy were randomized to alirocumab 75 to 150 mg or matching placebo every 2 weeks subcutaneously. Major adverse cardiovascular events (MACE) were examined in relation to continuous or dichotomous triglyceride concentrations. RESULTS: Median baseline triglyceride concentration was 129 mg/dL. In both treatment groups, a 10-mg/dL higher baseline concentration was associated with an adjusted MACE HR of 1.008 (95% CI: 1.003-1.013; P < 0.005). Baseline triglycerides ≥150 vs <150 mg/dL were associated with a HR of 1.184 (95% CI: 1.080-1.297; P < 0.005). Versus placebo, alirocumab reduced low-density lipoprotein cholesterol from baseline (average, 54.7%) and reduced MACE (HR: 0.85; 95% CI: 0.78-0.93). At month 4, triglyceride levels were reduced from baseline by median 17.7 mg/dL (P < 0.001) and 0.9 mg/dL (P = NS) with alirocumab and placebo, respectively. A 10-mg/dL decline from baseline in triglycerides was associated with lower subsequent risk of MACE with placebo (HR: 0.988; 95% CI: 0.982-0.995; P < 0.005) but not with alirocumab (HR: 0.999; 95% CI: 0.987-1.010; P = 0.82). CONCLUSIONS: Among patients with recent ACS on optimized statin therapy, baseline triglycerides was associated with cardiovascular risk. However, the reduction in triglycerides with alirocumab did not contribute to its clinical benefit. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
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Síndrome Coronario Agudo , Anticuerpos Monoclonales Humanizados , Triglicéridos , Humanos , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/sangre , Anticuerpos Monoclonales Humanizados/uso terapéutico , Masculino , Femenino , Triglicéridos/sangre , Persona de Mediana Edad , Anciano , Método Doble Ciego , Resultado del Tratamiento , Inhibidores de PCSK9/uso terapéutico , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/prevención & controlRESUMEN
Importance: Prior trials showed that dual antiplatelet therapy could reduce the risk of early new stroke in patients with acute mild ischemic stroke or transient ischemic attack (TIA) within 24 hours of symptom onset. However, it is currently uncertain whether dual antiplatelet therapy can reduce the risk of early new stroke in patients with a more delayed initiation time window. Objective: To evaluate the efficacy and safety of clopidogrel and aspirin among patients with mild ischemic stroke or TIA when initiated within 24 hours, from more than 24 hours to 48 hours, and from more than 48 hours to 72 hours. Design, Setting, and Participants: The Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis randomized clinical trial was a double-blind, placebo-controlled, multicenter, 2-by-2 factorial randomized clinical trial conducted at 222 hospitals in China from September 17, 2018, to October 15, 2022. All patients with acute mild ischemic stroke and TIA were included in this subgroup analysis and categorized into 3 groups according to time from symptom onset to randomization (group 1: ≤24 hours; group 2: >24 to ≤48 hours; and group 3: >48 to 72 hours). Patients were followed up for 90 days. Interventions: All patients received clopidogrel combined with aspirin (clopidogrel 300 mg loading dose on day 1, followed by 75 mg daily on days 2 to 90, and aspirin 100 to 300 mg on the first day and then 100 mg daily for days 2 to 90) or aspirin alone (100 to 300 mg on day 1 and then 100 mg daily for days 2 to 90) within 72 hours after symptom onset. Main Outcomes and Measures: The primary outcome was new stroke (ischemic or hemorrhagic) within 90 days. The primary safety outcome was moderate-to-severe bleeding, according to Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries criteria. Results: This analysis included a total of 6100 patients (3050 in the clopidogrel-aspirin group and 3050 in the aspirin group). The median age was 65 years (IQR, 57-71 years), and 3915 patients (64.2%) were male. In the population with time to randomization of 24 hours or less, stroke occurred in the next 90 days in 97 of 783 patients (12.4%); among those randomized from more than 24 hours to 48 hours, in 211 of 2552 patients (8.3%) among those randomized from more than 24 hours to 48 hours, and in 193 of 2765 patients (7.0%). The clopidogrel-aspirin group had a lower risk of new stroke within 90 days compared with the aspirin alone group both in patients with time to randomization of from 48 to 72 hours (5.8% vs 8.2%; hazard ratio [HR], 0.70 [95% CI, 0.53-0.94]), of more than 24 to 48 hours (7.6% vs 8.9%; HR, 0.85 [95% CI, 0.65-1.12]), and of 24 hours or less (11.5% vs 13.4%; HR, 0.83 [95% CI, 0.55-1.25]) (P = .38 for interaction). Among those with time to randomization of more than 48 to 72 hours, moderate-to-severe bleeding occurred in 12 patients (0.9%) in the clopidogrel-aspirin group and in 6 patients (0.4%) in the aspirin-alone group (HR, 2.00 [95% CI, 0.73-5.43]), while moderate-to-severe bleeding in those with time to randomization of more than 24 hours to 48 hours occurred in 9 patients (0.7%) in the clopidogrel-aspirin group and in 4 patients (0.3%) in the aspirin-alone group (HR, 2.25 [95% CI, 0.68-7.39]) and in those with time to randomization of within 24 hours, occurred in 6 patients (1.5%) in the clopidogrel-aspirin group and in 3 patients (0.8%) in the aspirin-alone group (HR, 1.57 [95% CI, 0.36-6.83]) (P = .92 for interaction). Conclusions and Relevance: In this randomized clinical trial of antiplatelet therapy in China, patients with mild ischemic stroke or TIA had consistent benefit from dual antiplatelet therapy with clopidogrel and aspirin vs aspirin alone when initiated within 72 hours after symptom onset, with a similar increase in the risk of moderate-to-severe bleeding. Patients should receive dual antiplatelet therapy with clopidogrel and aspirin within 72 hours after symptom onset. Trial Registration: ClinicalTrials.gov Identifier: NCT03635749.
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Aspirina , Clopidogrel , Accidente Cerebrovascular Isquémico , Inhibidores de Agregación Plaquetaria , Humanos , Clopidogrel/uso terapéutico , Aspirina/uso terapéutico , Aspirina/administración & dosificación , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/prevención & control , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Anciano , Método Doble Ciego , Ataque Isquémico Transitorio/tratamiento farmacológico , China/epidemiología , Tiempo de Tratamiento/estadística & datos numéricos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Importance: Colchicine has many drug-drug interactions with commonly prescribed medications. Only pharmacokinetic studies have provided data on colchicine drug-drug interactions. Objective: To evaluate the clinical tolerability of colchicine according to the presence or absence of a drug-drug interaction. Design, Setting, and Participants: A secondary analysis of the COLCORONA trial was performed. The COLCORONA trial was a randomized, double-blind, placebo-controlled trial conducted in Brazil, Canada, Greece, South Africa, Spain, and the US between March 23, 2020, and January 20, 2021. The COLCORONA trial included ambulatory patients with COVID-19 with at least 1 high-risk characteristic and compared the effects of colchicine (0.5 mg twice daily for 3 days, then 0.5 mg daily thereafter) with placebo for 27 days. Data analysis was performed from February 24, 2023, to June 20, 2024. Exposure: In this secondary analysis, baseline medications that had interactions with colchicine were identified using a previously published expert classification. Main Outcomes and Measures: The primary outcome for this analysis was the composite of serious and nonserious treatment-related and treatment-unrelated gastrointestinal adverse events. The secondary outcomes were other adverse events and the composite of death or hospital admission due to COVID-19 infection. Logistic regression models adjusted for age, sex, estimated glomerular filtration rate, diabetes, heart failure, and myocardial infarction were assessed for effect modification of the association between the randomization arm and the outcomes of interest by drug-drug interaction status. Results: The cohort included 2205 participants in the colchicine arm and 2227 in the placebo arm (median age, 54 [IQR, 47-61] years; 2389 [54%] women). The most common colchicine drug-drug interactions were rosuvastatin (12%) and atorvastatin (10%). In fully adjusted models, the odds of any gastrointestinal adverse event were 1.80 (95% CI, 1.51-2.15) times higher in the colchicine arm than the placebo arm among people without a drug-drug interaction and 1.68 (95% CI, 1.24-2.26) times higher in the colchicine arm than the placebo arm among people with a drug-drug interaction (P = .69 for interaction). Drug-drug interaction status did not significantly modify the effect of colchicine on the composite of COVID-19 hospitalization or death (odds ratio, 0.91; 95% CI, 0.59-1.40 for drug-drug interaction and 0.84; 95% CI, 0.60-1.19 for no drug-drug interaction; P = .80 for interaction). Conclusions and Relevance: In this secondary analysis of the COLCORONA trial, operational classification of drug interactions system class 3 or 4 drug-drug interactions did not appear to significantly increase the risk of colchicine-related adverse effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04322682.
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COVID-19 , Colchicina , Interacciones Farmacológicas , SARS-CoV-2 , Humanos , Colchicina/efectos adversos , Colchicina/uso terapéutico , Colchicina/farmacocinética , Femenino , Masculino , Persona de Mediana Edad , Método Doble Ciego , Anciano , Tratamiento Farmacológico de COVID-19 , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , PandemiasRESUMEN
BACKGROUND: Off-label intranasal administration of injectable dexmedetomidine has been widely applied in the pediatric sedation setting. However, the development of an improved drug delivery system that is easy to use is needed. We developed a novel dexmedetomidine nasal spray that can be administered directly without dilution or configuration for pediatric pre-anesthetic sedation. This nasal spray has a fixed dose and is stable during storage. To the best of our knowledge, this is the first licensed nasal spray preparation of dexmedetomidine worldwide. OBJECTIVE: To evaluate the pre-anesthetic sedation efficacy and safety of the novel dexmedetomidine nasal spray in children. METHODS: The study was conducted at 11 sites in China between 24 November 2021 and 20 May 2022 and was registered in ClinicalTrials.gov (NCT05111431, first registration date: 20/10/2021). Subjects (n = 159) between 2 and 6 years old who were to undergo elective surgery were randomized to the dexmedetomidine group (n = 107) or the placebo group (n = 52) in a 2:1 ratio. The dosage was 30 µg or 50 µg based on the stratified body weight. The primary outcome measure was the proportion of subjects who achieved the desired child-parent separation and Ramsay scale ≥ 3 within 45 min of administration. Safety was monitored via the assessments of adverse events, blood pressure, heart rate, respiratory rate and blood oxygen saturation. RESULTS: The proportion of subjects achieving desired parental separation and Ramsay scale ≥ 3 within 45 min was significantly higher in the dexmedetomidine group (94.4%) vs the placebo group (32.0%) (P < 0.0001). As compared with placebo, dexmedetomidine treatment led to more subjects achieving Ramsay scale ≥ 3 or UMSS ≥ 2, and shorter time to reach desired parental separation, Ramsay scale ≥ 3 and UMSS ≥ 2 (all P < 0.0001). Adverse events were reported in 90.7% and 84.0% of subjects in the dexmedetomidine and placebo groups, respectively, and all the events were mild or moderate in severity. CONCLUSIONS: This novel dexmedetomidine nasal spray presented effective pre-anesthetic sedation in children with a tolerable safety profile.
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Dexmedetomidina , Hipnóticos y Sedantes , Rociadores Nasales , Humanos , Dexmedetomidina/administración & dosificación , Masculino , Femenino , Método Doble Ciego , Preescolar , Hipnóticos y Sedantes/administración & dosificación , Niño , Administración Intranasal , China , Medicación Preanestésica/métodosRESUMEN
Persistent subretinal fluid (PSF) after scleral bucking of rhegmatogenous retinal detachment may delay recovery and affect the final visual quality, but with no effective treatment. This study firstly investigated the safety and efficacy of 577 nm yellow subthreshold micropulse laser (SML) on PSF after scleral bucking surgery. This double-masked randomized clinical trial was conducted from December 2020 to October 2022 at Chongqing Aier Eye Hospital. Participants with PSF last for 1 month after scleral bucking surgery with break closed and retina reattachment were recruitment. These participants were treated by 577 nm yellow SML or sham treatment. Funduscopy, optical coherence tomography (OCT) volume change, best corrected vision acuity (BCVA) and visual field test were evaluated for six mouths follow-up. A total of 24 participants were randomized into SML group or Sham group equally. Compared with Sham group, the OCT volume within 6 mm of macular fovea was significantly less in SML group 6 months after therapy (P = 0.048). There were no statistically significant differences of OCT volume at 1, 2 and 3 months from baseline between groups. BCVA of ETDRS letters had no statistically significant difference. Pattern Standard Deviation amelioration (P = 0.039) had statistically significance in SML group compared with Sham group. There were no complications in the 2 groups. These preliminary findings suggest that 577 nm yellow SML therapy could accelerate PSF absorption after scleral bucking surgery.Trial registration: Chinese Clinical Trial Registry No. ChiCTR2000037838, 02/09/2020, https://www.chictr.org.cn/showproj.html?proj=51885 .
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Desprendimiento de Retina , Curvatura de la Esclerótica , Líquido Subretiniano , Tomografía de Coherencia Óptica , Agudeza Visual , Humanos , Femenino , Masculino , Curvatura de la Esclerótica/métodos , Curvatura de la Esclerótica/efectos adversos , Desprendimiento de Retina/cirugía , Persona de Mediana Edad , Tomografía de Coherencia Óptica/métodos , Adulto , Resultado del Tratamiento , Método Doble CiegoRESUMEN
Following on from our pilot studies, this study aimed to test the efficacy of a combination of probiotics (Lactobacillus acidophilus, Bifidobacterium bifidum, Streptococcus thermophilus), magnesium orotate and coenzyme 10 for the treatment of major depressive disorder (MDD) through a double-blind placebo controlled clinical trial. The participants were 120 adults diagnosed with MDD randomised to daily oral administration, over 8 weeks, of either the intervention or placebo, with a 16-week follow-up period. Intent-to-treat analysis found a significantly lower frequency of the presence of a major depressive episode in the intervention group compared with placebo at the end of the 8-week treatment phase, with no difference between the two conditions at 8-week follow-up. Both the categorical and continuous measure of depressive symptoms showed a significant difference between the two conditions at 4 weeks, but not 8 and 16 weeks. The secondary end-point was demonstrated with an overall reduction in self-rated symptoms of anxiety and stress in the active treatment group compared with placebo. These findings suggest that the combination of probiotics, magnesium orotate and coenzyme 10 may be an effective treatment of MDD over an 8-week period.
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Trastorno Depresivo Mayor , Probióticos , Humanos , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/terapia , Masculino , Femenino , Adulto , Método Doble Ciego , Persona de Mediana Edad , Resultado del Tratamiento , Lactobacillus acidophilus , Bifidobacterium bifidum , Streptococcus thermophilusRESUMEN
BACKGROUND: Breakthrough cancer pain (BTcP) has a negative impact on patients' quality of life, general activities, and is related to worse clinical outcomes. Fentanyl inhalant is a hand-held combination drug-device delivery system providing rapid, multi-dose (25µg/dose) administration of fentanyl via inhalation of a thermally generated aerosol. This multicenter, randomized, placebo-controlled, multiple-crossover, double-blind study evaluated the efficacy, safety, and tolerability of fentanyl inhalant in treating BTcP in opioid-tolerant patients. METHODS: The trial was conducted in opioid-tolerant cancer patients with 1 ~ 4 BTcP outbursts per day. Each patient was treated and observed for 6 episodes of BTcP (4 with fentanyl inhalant, 2 with placebo). During each episode of targeted BTcP, patients were allowed up to six inhalations, with an interval of at least 4 min between doses. Primary outcome was the time-weighted sum of PID (pain intensity difference) scores at 30 min (SPID30). RESULTS: A total of 335 BTcP episodes in 59 patients were treated. The mean SPID30 was -97.4 ± 48.43 for fentanyl inhalant-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes (p < 0.001). Significant differences in PID for episodes treated with fentanyl inhalant versus placebo was seen as early as 4 min and maintained for up to 60 min. The percentage of episodes reported PI (pain intensity) scores ≤ 3, a ≥ 33% or ≥ 50% reduction in PI scores at 30 min, PR30 (pain relief scores at 30 min) and SPID60 favored fentanyl inhalant over placebo. Only 4.4% of BTcP episodes required rescue medication in fentanyl inhalant group. Most AEs were of mild or moderate severity and typical of opioid drugs. CONCLUSION: Treatment with fentanyl inhalant was shown to be a promising therapeutic option for BTcP, with significant pain relief starting very soon after dosing. Confirmation of effectiveness requires a larger phase III trial. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05531422 registered on 6 September 2022 after major amendment, NCT04713189 registered on 14 January 2021.
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Analgésicos Opioides , Dolor Irruptivo , Dolor en Cáncer , Fentanilo , Humanos , Fentanilo/uso terapéutico , Fentanilo/farmacología , Fentanilo/administración & dosificación , Método Doble Ciego , Masculino , Persona de Mediana Edad , Femenino , Analgésicos Opioides/uso terapéutico , Analgésicos Opioides/administración & dosificación , Dolor Irruptivo/tratamiento farmacológico , Dolor Irruptivo/etiología , Anciano , Dolor en Cáncer/tratamiento farmacológico , Adulto , Administración por Inhalación , Estudios Cruzados , Dimensión del Dolor/métodos , Resultado del Tratamiento , Anciano de 80 o más AñosRESUMEN
BACKGROUND: Equivalent efficacy and comparable pharmacokinetic, immunogenicity, and safety profiles of the biosimilar BAT1806/BIIB800 and reference tocilizumab (TCZ) in participants with moderate-to-severe rheumatoid arthritis (RA) have been reported up to week 24 (treatment period [TP] 1) of the phase 3 study. Here we present results for TP2 (study weeks 24-48). METHODS: In this phase 3, multicenter, multiregional, double-blind, active-controlled, equivalence study, participants with active RA despite methotrexate were randomized (1:1:2) to intravenous administration of 8 mg/kg TCZ every 4 weeks to week 48 (TCZ group), or TCZ to week 24 followed by BAT1806/BIIB800 to week 48 (TCZ to BAT1806/BIIB800 group), or BAT1806/BIIB800 to week 48 (BAT1806/BIIB800 group). Efficacy in TP2 was evaluated using American College of Rheumatology (ACR) response criteria (ACR20/50/70) and change from baseline in Disease Activity Score on 28 joints (DAS28). Pharmacokinetics (trough levels), safety, and immunogenicity were also evaluated. RESULTS: Of 621 randomized participants, 577 (92.9%) completed TP1 and entered TP2 (TCZ: N = 145 [93.5%]; TCZ to BAT1806/BIIB800: N = 142 [92.2%]; BAT1806/BIIB800: N = 290 [92.9%]). Proportions of ACR20 responders were similar between treatment groups throughout TP2 (87.8%, 90.3%, and 90.4%, respectively, at week 48), as were proportions of ACR50 and ACR70 responders, and reduction in DAS28. Drug trough levels and antidrug antibody incidences were comparable between the treatment groups. Adverse events were balanced across the treatment groups and no fatal events were reported. CONCLUSION: In TP2, efficacy, safety, immunogenicity, and pharmacokinetic profiles were comparable between the TCZ, TCZ to BAT1806/BIIB800, and BAT1806/BIIB800 groups. TRIAL REGISTRATION: NCT03830203 and EudraCT 2018-002202-31.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Antirreumáticos , Artritis Reumatoide , Biosimilares Farmacéuticos , Metotrexato , Humanos , Artritis Reumatoide/tratamiento farmacológico , Masculino , Metotrexato/uso terapéutico , Metotrexato/farmacocinética , Metotrexato/administración & dosificación , Femenino , Método Doble Ciego , Persona de Mediana Edad , Biosimilares Farmacéuticos/farmacocinética , Biosimilares Farmacéuticos/uso terapéutico , Biosimilares Farmacéuticos/administración & dosificación , Biosimilares Farmacéuticos/efectos adversos , Antirreumáticos/farmacocinética , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Adulto , Anticuerpos Monoclonales Humanizados/farmacocinética , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Resultado del Tratamiento , Anciano , Índice de Severidad de la EnfermedadRESUMEN
RATIONALE: Central neuropathic pain resulting from spinal cord injury is notoriously debilitating and difficult to treat with few currently available treatments. A novel molecule with intrathecal administration: Ziconotide has been approved for treatment of refractory neuropathic pain in general. It acts as a presynaptic calcium channel blocker. A pilot study has shown its potential in SCI neuropathic pain patients. OBJECTIVE: The aim of this study is to determine the long-term (6 months) efficacy of chronic intrathecal ziconotide for the treatment of neuropathic SCI pain. STUDY DESIGN: Multicenter, Randomized, Comparative, Placebo controlled, Double blind clinical trial, with a crossover of random alternated periods of 6 months (placebo or ITZ) for a total of 15 months including a total of 44 patients. STUDY POPULATION: ⢠Patients with SCI of various etiologies exhibiting neuropathic pain refractory to non-invasive treatments. ⢠> 18 years. INTERVENTION: Intrathecal administration of ziconotide via an implanted pump. STUDY OUTCOMES: Primary study outcome Difference in pain intensity for all patients between effective treatment and placebo periods. Secondary study outcomes 1. Continuous evaluation of pain intensity. 2. Percentage of patients with at least 30% of pain reduction. 3. Satisfaction level of the patient pain relief. 4. Declarations of serious adverse events. 5. Duration and intensity of spontaneous and provoked pain. 6. Quality of life. 7. Patient global impression of change. 8. Quantification of daily dosages of analgesic drug intake. 9. Long term memory and neurocognitive effects. 10. Assessment of the patient's physical and emotional distress. NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT, AND GROUP RELATEDNESS: Participation in this study is in accordance with current treatment protocols for SCI neuropathic pain in France therefore it proposes a treatment that would currently be considered regular practice even though no RCT evidence is yet available. The study gives patients the advantage of directly testing versus placebo a treatment that otherwise entails significant constraints. A Data Safety Monitoring board (DSMB) will be created for continuous safety analysis. Furthermore, patients will be followed in specialized pain centers offering the possibility of continuing their treatment after the study period.
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Estudios Cruzados , Inyecciones Espinales , Neuralgia , Dimensión del Dolor , Traumatismos de la Médula Espinal , omega-Conotoxinas , Humanos , Analgésicos no Narcóticos/administración & dosificación , Analgésicos no Narcóticos/uso terapéutico , Método Doble Ciego , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Neuralgia/diagnóstico , omega-Conotoxinas/administración & dosificación , omega-Conotoxinas/efectos adversos , Satisfacción del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Índice de Severidad de la Enfermedad , Traumatismos de la Médula Espinal/complicaciones , Factores de Tiempo , Resultado del Tratamiento , Estudios Multicéntricos como AsuntoAsunto(s)
Dermatitis Atópica , Melatonina , Índice de Severidad de la Enfermedad , Calidad del Sueño , Adolescente , Niño , Preescolar , Femenino , Humanos , Masculino , Dermatitis Atópica/tratamiento farmacológico , Método Doble Ciego , Melatonina/administración & dosificación , Melatonina/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) is a new avenue for treating migraine. The efficacy and safety of intravenous Lu AG09222, a humanized monoclonal antibody directed against the PACAP ligand, for migraine prevention are unclear. METHODS: In a phase 2, double-blind, randomized, placebo-controlled trial, we enrolled adult participants (18 to 65 years of age) with migraine for whom two to four previous preventive treatments had failed to provide a benefit. The trial included a 4-week treatment period and an 8-week follow-up period. Participants were randomly assigned in a 2:1:2 ratio to receive a single-dose baseline infusion of 750 mg of Lu AG09222, 100 mg of Lu AG09222, or placebo. The primary end point was the mean change from baseline in the number of migraine days per month, during weeks 1 through 4, in the Lu AG09222 750-mg group as compared with the placebo group. RESULTS: Of 237 participants enrolled, 97 received 750 mg of Lu AG09222, 46 received 100 mg of Lu AG09222, and 94 received placebo. The mean number of baseline migraine days per month was 16.7 in the overall population, and the mean change from baseline over weeks 1 through 4 was -6.2 days in the Lu AG09222 750-mg group, as compared with -4.2 days in the placebo group (difference, -2.0 days; 95% confidence interval, -3.8 to -0.3; P = 0.02). Adverse events with a higher incidence in the Lu AG09222 750-mg group than in the placebo group during the 12-week observation period included coronavirus disease 2019 (7% vs. 3%), nasopharyngitis (7% vs. 4%), and fatigue (5% vs. 1%). CONCLUSIONS: In a phase 2 trial, a single intravenous infusion of 750 mg of Lu AG09222 showed superiority over placebo in reducing migraine frequency over the subsequent 4 weeks. (Funded by H. Lundbeck; HOPE ClinicalTrials.gov number, NCT05133323.).
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Anticuerpos Monoclonales Humanizados , Trastornos Migrañosos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Método Doble Ciego , Infusiones Intravenosas , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/antagonistas & inhibidores , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Brote de los SíntomasRESUMEN
The use of skin barrier-enhancing topical medication is a favorable approach for the treatment of occupational hand dermatitis (OHD). Cocos nucifera or coconut oil is one of the best sources of lipid enriched with laurate acid, and glycerin is a well-known humectant that improves skin hydration. This study is aimed is to evaluate the effectiveness of C. nucifera and glycerin for secondary prevention of OHD among batik (Indonesian traditional fabric) workers. In a randomized, double-blind, crossover trial, the effect of glycerine-C. nucifera cream versus glycerin-only was considered with multiple afterwork applications of moisturizer over a 2-week period on batik workers with OHD. Assessment of trans-epidermal water loss (TEWL), skin capacitance, and a clinical assessment using the Hand Eczema Severity Index (HECSI) were carried out at day 0 and 14. The results show thirty-two batik dyeing and/or rinsing workers were enrolled in the study with mild to moderate OHD. Clinical improvement was demonstrated by 20% decrease in HECSI and TEWL, and 20% increase in skin capacitance. Both moisturizers were equally effective for the secondary prevention of OHD. As a conclusion, glycerine-C. nucifera and glycerin-only cream are equally effective for secondary prevention for OHD among batik worker to reduce the prevalence of hand dermatitis.
Asunto(s)
Cocos , Estudios Cruzados , Emolientes , Glicerol , Humanos , Adulto , Masculino , Método Doble Ciego , Femenino , Cocos/química , Emolientes/administración & dosificación , Emolientes/uso terapéutico , Persona de Mediana Edad , Dermatitis Profesional/prevención & control , Dermatitis Profesional/etiología , Dermatosis de la Mano/prevención & control , Dermatosis de la Mano/tratamiento farmacológico , Crema para la Piel/administración & dosificación , Crema para la Piel/uso terapéutico , Prevención Secundaria/métodosRESUMEN
BACKGROUND: The serotonin type 7 (5-HT7) receptor is one of 14 5-HT receptors. It has received attention for its possible role in mood disorders and cognition. The 5-HT7 receptor antagonist, JNJ-18038683, has been reported to be effective in rodent models of depression and REM sleep. Also, 5-HT7 receptor blockade has been postulated to be a key component of cognitive enhancement in a number of drugs. Bipolar disorder (BD) usually endures cognitive impairment (CI); however, no treatment for CI in BD has been approved. This study aimed to evaluate the efficacy of JNJ-18038683 to improve the CI of BD compared to a placebo. METHODS: We conducted a placebo-controlled, 8-week trial of JNJ-18038683 in BD patients. Each patient's data were analyzed and reassessed blindly with a comprehensive neuropsychological battery, depression and hypomania ratings, and overall social and work function measures. RESULTS: Of 60 patients, 38 (63%) were female, 43 (72%) had BD type 1, and most patients were Caucasian and married. The overall time effect for the combined group shows statistically significant improvement from baseline to week 8 for most of the neurocognitive battery measures. This indicates a significant improvement in psychopathology and cognition during the study time in both JNJ-18038683 and placebo groups, but no difference between groups. CONCLUSIONS: This study showed no efficacy for the improvement of CIBD or mood symptoms with JNJ-18038683 compared to the placebo.
Asunto(s)
Trastorno Bipolar , Humanos , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/complicaciones , Femenino , Masculino , Adulto , Persona de Mediana Edad , Método Doble Ciego , Receptores de Serotonina/efectos de los fármacos , Antagonistas de la Serotonina/farmacología , Antagonistas de la Serotonina/administración & dosificación , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/etiología , Resultado del Tratamiento , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Catheter-associated urinary tract infection (CAUTI) remains the most significant challenge among hospital-acquired infections (HAIs), yet still unresolved. The present study aims to evaluate the preventive effectiveness of JUC Spray Dressing (name of U.S. FDA and CE certifications, while the medical device name in China is Long-acting Antimicrobial Material) alone for CAUTI without combining with antibiotics and to evaluate the impact of bacterial biofilm formation on CAUTI results on the inserted catheters of patients. METHODS: In this multicenter, randomized, double-blind study, we enrolled adults who suffered from acute urinary retention (AUR) and required catheterization in 6 hospitals in China. Participants were randomly allocated 1:1 according to a random number table to receive JUC Spray Dressing (JUC group) or normal saline (placebo group). The catheters were pretreated with JUC Spray Dressing or normal saline respectively before catheterization. Urine samples and catheter samples were collected after catheterization by trial staff for further investigation. RESULTS: From April 2012 to April 2020, we enrolled 264 patients and randomly assigned them to the JUC group (n = 132) and the placebo group (n = 132). Clinical symptoms and urine bacterial cultures showed the incidence of CAUTI of the JUC group was significantly lower than the placebo group (P < 0.01). In addition, another 30 patients were enrolled to evaluate the biofilm formation on catheters after catheter insertion in the patients' urethra (10 groups, 3 each). The results of scanning electron microscopy (SEM) showed that bacterial biofilm formed on the 5th day in the placebo group, while no bacterial biofilm formed on the 5th day in the JUC group. In addition, no adverse reactions were reported using JUC Spray Dressing. CONCLUSION: Continued indwelling urinary catheters for 5 days resulted in bacterial biofilm formation, and pretreatment of urethral catheters with JUC Spray Dressing can prevent bacterial biofilm formation by forming a physical antimicrobial film, and significantly reduce the incidence of CAUTI. This is the first report of a study on inhibiting bacterial biofilm formation on the catheters in CAUTI patients.