RESUMO
BACKGROUND/AIM: The aim of this study was to evaluate the safety and efficacy of AFree oral spray, in combination with Standard of Care, in treating mild to moderate COVID-19 patients. This was an open-label, single-blinded, and controlled randomized clinical trial. PATIENTS AND METHODS: The study involved 1,252 patients, who were randomly assigned to either the control or study group, with 626 patients in each group. Patients in the control group were treated with Standard of Care recommended by the Ministry of Health of Vietnam, while patients in the study group received AFree oral spray in addition to Standard of Care for a period of 10 days. The clinical progression and outcomes of both groups were compared. RESULTS: The results showed that the proportion of patients with clinical symptoms on the 5th, 7th and 10th days were significantly lower in the study group (45.05%, 3.19% and 0%, respectively) compared to the control group (86.10%, 67.73% and 22.84%, respectively). Additionally, the rate of Real-time PCR test positivity for COVID-19 was significantly lower in the study group compared to the control group on the 4th, 7th, and 10th days (82.75% vs. 98.72%, 9.27% vs. 92.97%, and 1.12% vs. 50.48%, respectively). Furthermore, no side effects or complications related to AFree oral spray were recorded in the study group. CONCLUSION: The use of AFree oral spray resulted in significant improvements in clinical symptoms, recovery time, and viral clearance in COVID-19 patients with mild to moderate symptoms. This therapy has been shown to be safe and can be used as an adjuvant treatment for COVID-19 as well as other respiratory viral infections.
Assuntos
COVID-19 , Humanos , Estudos Prospectivos , Sprays Orais , SARS-CoV-2 , Saúde Pública , Progressão da Doença , Resultado do TratamentoRESUMO
BACKGROUND: This retrospective study evaluates patient-reported outcomes in patients with multiple sclerosis (MS) spasticity who were treated with a cannabinoid oromucosal spray (Sativex®, USAN name: nabiximols) after not sufficiently responding to previous anti-spasticity medications. METHODS: Of 276 patients from eight centers in Belgium who began treatment prior to 31 December 2017, effectiveness assessment data were available for 238 patients during the test period of 4 to 8/12 weeks, and for smaller patient cohorts with continued treatment for 6/12 months. RESULTS: Mean 0-10 spasticity Numerical Rating Scale (NRS) scores improved from 8.1 at baseline to 5.2 (week 4), 4.6 (week 8) and 4.1 (week 12). Mean EuroQoL Visual Analogue Scale (EQ VAS) scores increased from 39 at baseline to 52 (week 4), 57 (week 8) and 59 (week 12). Mean NRS and EQ VAS scores remained in the same 12 weeks' range in patients with longer-term data. The average dose of cannabinoid oromucosal spray was 6 sprays/day. Most of the 93 out of 276 patients, with initial prescription (33.7%), who discontinued treatment by week 12 did so within the first 8 weeks, mainly due to lack of effectiveness. By week 12, 171 (74%) of the 230 effectiveness evaluable patients reported a clinically meaningful response, corresponding to ≥30% NRS improvement. The tolerability of cannabinoid oromucosal spray was consistent with its known safety profile. CONCLUSIONS: More than 60% of the patients with MS who started add-on treatment with cannabinoid oromucosal spray reported a clinically relevant symptomatic effect and continued treatment after 12 weeks.
Assuntos
Canabidiol/uso terapêutico , Canabinoides/uso terapêutico , Dronabinol/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Bélgica , Esquema de Medicação , Combinação de Medicamentos , Humanos , Esclerose Múltipla/complicações , Esclerose Múltipla/patologia , Espasticidade Muscular/etiologia , Espasticidade Muscular/patologia , Sprays Orais , Medidas de Resultados Relatados pelo Paciente , Extratos Vegetais/uso terapêutico , Qualidade de Vida , Estudos Retrospectivos , Índice de Gravidade de DoençaRESUMO
Objective: The aim of this study was to evaluate the efficiency of a buccal spray form of vitamin D compared to single oral dose (stoss therapy) and oral drops therapy in the treatment of vitamin D deficiency. Methods: Ninety healthy children and adolescents (3-18 years) with vitamin D deficiency [serum level of 25-hydroxyvitamin D (25(OH) D) <12 ng/mL] were randomized to receive vitamin D3 buccal spray (2000 U, n=30, group 1) for six weeks, oral drops (2000 U, n=30, group 2) for six weeks and a single oral dose (300 000 U) vitamin D3 (n=30, group 3). Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone and 25(OH)D levels of the patients were measured at baseline and after the treatment on the 42nd day. Results: All three groups had a significant increase in serum 25(OH)D concentrations (p<0.001). In group 1, baseline mean 25(OH)D was 8.0±0.41 ng/mL, which rose to 22.1 (17.8-28.2) ng/mL after treatment with a mean increase of 15.6±1.3 ng/mL. Similarly in group 2, baseline, post-treatment and mean increase in 25(OH)D concentrations were 7.9±0.45 ng/mL, 24.4 (20.6-29.6) ng/mL and 17.3±1.1 ng/mL while for group 3 these values were 7.6±0.47 ng/mL, 40.3 (29.4-58.4) ng/mL and 34.3±3.2 ng/mL, respectively. Conclusion: We conclude that vitamin D3 supplementation with buccal spray and oral drops is equally effective in terms of raising vitamin D concentrations in short-term treatment of vitamin D deficiency.
Assuntos
Colecalciferol/farmacologia , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/tratamento farmacológico , Administração Bucal , Adolescente , Criança , Pré-Escolar , Colecalciferol/administração & dosagem , Feminino , Humanos , Masculino , Sprays Orais , Resultado do TratamentoRESUMO
Dry mouth, hyposalivation, or xerostomia is a significant problem in diabetic patients; however, there has been no way to relieve these symptoms. This study's aim was to evaluate the effects of Ixeris dentata (IXD) in combination with lactobacillus extract on the salivation rate in diabetes-induced dry mouth, and its mechanism was also investigated. In the streptozotocin (STZ)-induced diabetes model, the dry mouth condition was established as a model. Here, rats were treated with water or IXD through the sublingual spray, and subsequently treated with or without a spray of lactobacillus extract. In diabetes condition, the salivary flow rate, amylase activity, and aquaporin-5 and Na+/H+ exchanger (NHE-1) expressions were markedly decreased, whereas they were more significantly recovered in the sequential treatment of IXD-lactobacillus extract than in each single treatment. Furthermore, oxidative stress and its related ER stress response were especially regulated in the IXD/lactobacillus extract condition, where the following anti-oxidative enzymes, glutathione assay (GSH: GSSG) ratio, superoxide dismutase (SOD), and glutathione peroxidase (GPx), were involved. This study suggests that the combination of IXD and lactobacillus would be a potential alternative medicine against diabetes-induced hyposalivation and xerostomia.
Assuntos
Asteraceae/química , Diabetes Mellitus Experimental/complicações , Lactobacillus gasseri , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Salivação/efeitos dos fármacos , Xerostomia/tratamento farmacológico , Xerostomia/etiologia , Administração Sublingual , Animais , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Lactobacillus gasseri/química , Sprays Orais , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Xerostomia/fisiopatologiaRESUMO
(1) Background: Vitamin D deficiency is an important public health concern and supplementation is common for this deficiency. Many different modes of delivering supplementation have been proposed in order to enhance absorption and utilization. The present review compared the efficacy of vitamin D3 buccal spray against other forms of supplementation delivery. (2) Methods: The protocol was registered at PROSPERO (CRD42019136146). Medline/PubMed, CENTRAL and clinicaltrials.gov were searched from their inception until September 2019, for randomized controlled trials (RCTs) that compare vitamin D3 delivery via sublingual spray against other delivery methods. Eligible RCTs involved humans, of any age and health status, published in any language that evaluated changes in plasma 25(OH)D concentrations. Three reviewers independently extracted data, assessed risk of bias (RoB) and the quality of the trials. (3) Results: Out of 9759 RCTs, four matched the predefined criteria. Intervention duration ranged from 30 days to 3 months whereas vitamin D3 dosage ranged between 800 and 3000 IU/day. One RCT advocated for the superiority of buccal spray in increasing plasma 25(OH)D concentrations, although several limitations were recorded in that trial. The rest failed to report differences in post-intervention 25(OH)D concentrations between delivery methods. Considerable clinical heterogeneity was observed due to study design, intervention duration and dosage, assays and labs used to perform the assays, population age and health status, not allowing for synthesis of the results. (4) Conclusions: Based on the available evidence, delivery of vitamin D3 via buccal spray does not appear superior to the other modes of delivery. Future RCTs avoiding the existing methodological shortcomings are warranted.
Assuntos
Colecalciferol/administração & dosagem , Suplementos Nutricionais , Deficiência de Vitamina D/tratamento farmacológico , Vias de Administração de Medicamentos , Feminino , Humanos , Masculino , Sprays Orais , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Deficiência de Vitamina D/sangueRESUMO
The phytocannabinoid-based medicine Sativex® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), Δ9-tetrahydrocannabinol (Δ9-THC) and its metabolite 11-hydroxy-Δ9-THC. Maximal plasma concentrations of both Δ9-THC (Cmax = 18.5 ng/mL) and CBD (Cmax = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (Δ9-THC: Cmax = 24.5 ng/mL; CBD: Cmax = 15.2 ng/mL). 11hydroxy-Δ9-THC, which is mainly formed in the liver from Δ9-THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and Δ9-THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1-2 h and suggested progressive accumulation after the multiple dose treatment.
Assuntos
Analgésicos/administração & dosagem , Analgésicos/farmacocinética , Canabidiol/administração & dosagem , Canabidiol/farmacocinética , Dronabinol/administração & dosagem , Dronabinol/farmacocinética , Administração Sublingual , Analgésicos/sangue , Animais , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Canabidiol/sangue , Doenças do Cão , Cães , Dronabinol/sangue , Combinação de Medicamentos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Sprays Orais , Extratos Vegetais/administração & dosagem , Extratos Vegetais/sangue , Extratos Vegetais/farmacocinética , Taxa Respiratória/efeitos dos fármacosRESUMO
BACKGROUND: Vitamin D is critical for skeletal health, and is increasingly associated with other pathologies encompassing gastrointestinal, immunological and psychological effects. A significant proportion of the population exhibits suboptimal levels of vitamin D, particularly in Northern latitudes in winter. Supplementation is advocated, but few data are available on achievable or typical rates of change. There has been considerable interest in the potential use of sublingual sprays for delivery of nutrient supplements, but data on efficacy remain sparse. METHODS: A randomised, placebo-controlled, three-arm parallel design study was conducted in healthy volunteers (n = 75) to compare the rate of change of vitamin D status in response to vitamin D3 (3000 IU/day) supplementation in capsule and sublingual spray preparations over a 6-week period between January and April 2017. Blood 25(OH)D concentrations were measured after day 0, 3, 7, 14, 21 and 42 days of supplementation with 3000 IU per diem. RESULTS: Baseline measurements show 25(OH)D deficiency (<30 nmol/l), insufficiency (31-46 nmol/l) and sufficiency (> 50 mmol/l) in 14.9, 44.6 and 40.5% of the participants, respectively. There was a significant elevation in blood concentrations of 25(OH)D in both of the treatment arms (capsule p = 0.003, spray p = 0.001) compared with control. The capsule and spray were equally efficacious. The rate of change ranged from 0.69 to 3.93 (capsule) and 0.64 to 3.34 (spray) nmol/L day with average change in blood 25(OH)D levels of 2 nmol/l/day. Rates followed a simple normal distribution in the study population (ks = 0.94 and 0.82 for capsule and spray, respectively). The data suggest that rates of change are higher in individuals with lower levels of 25(OH)D. CONCLUSIONS: A sublingual vitamin D spray is an effective mode of delivery for supplementation in a healthy population. The data provide reference values and ranges for the rate of change of 25(OH)D for nutrikinetic analyses.
Assuntos
Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Vitamina D/farmacocinética , Administração Sublingual , Adolescente , Adulto , Cápsulas , Feminino , Humanos , Masculino , Sprays Orais , Vitamina D/sangue , Adulto JovemRESUMO
PURPOSE: Group A beta-hemolytic Streptococcus (GABHS) causes a recurrent acute pharyngotonsillitis (RAPT) in children. Moreover, the repeated use of antibiotics contributes to its resistance. However, S. Salivarius 24SMB and S. oralis 89a were effective probiotics in other infections. Thus, we decided to evaluate this combination efficacy compared to placebo in RAPT. METHODS: Patients with microbiologically confirmed GABHS were enrolled in this randomized, placebo-controlled trial. They received the aforementioned combination or placebo as an oral spray. We investigated episodes of frequency and duration, need for antibiotics, school days lost, the treatment impact on life quality, treatment compliance and side effects during a 90-day treatment and a 6-month follow-up. RESULTS: We included 41 patients in each group. The mean number of GABHS infection was significantly lower during both study periods for the two groups. However, our treatment group showed a lower rate. Moreover, the probiotic group had a lower mean number and a shorter median duration of GABHS episodes during both study periods than controls. Furthermore, the mean duration of antibiotic treatment was lower in the probiotic group during the 90-day and 6-month follow-up periods. Similarly, patients in the probiotic group showed a significantly lower mean number of absence days from school but higher EQ-VAS score. Indeed, all patients included were compliant to treatment. CONCLUSIONS: We identified potential probiotics, possessing desirable features against GABHS pharyngotonsillitis. Our findings represent the first evidence which throws the light on using these probiotics that can reduce antibiotics use which did not have efficient results regarding recurrence.
Assuntos
Terapia Biológica/métodos , Probióticos/uso terapêutico , Infecções Estreptocócicas/terapia , Streptococcus agalactiae , Streptococcus oralis , Streptococcus salivarius , Tonsilite/terapia , Adolescente , Antibacterianos/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Masculino , Sprays Orais , Faringite/microbiologia , Faringite/terapia , Probióticos/administração & dosagem , Recidiva , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Tonsilite/microbiologiaRESUMO
REVIEW QUESTIONS: The questions of this review are.
Assuntos
Pesquisa Comparativa da Efetividade/métodos , Suplementos Nutricionais/provisão & distribuição , Vitamina D/análogos & derivados , Vitamina D/administração & dosagem , Administração Oral , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados não Aleatórios como Assunto , Sprays Orais , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitamina D/sangue , Revisões Sistemáticas como AssuntoRESUMO
CONTEXT: Prior Phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain. OBJECTIVES: To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol [27 mg/mL] and cannabidiol [25 mg/mL]), in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy. METHODS: Phase 3, double-blind, randomized, placebo-controlled trial in patients with advanced cancer and average pain Numerical Rating Scale scores ≥4 and ≤8 despite optimized opioid therapy. Patients randomized to nabiximols (n = 199) or placebo (n = 198) self-titrated study medications over a two-week period, followed by a three-week treatment period at the titrated dose. RESULTS: Median percent improvements in average pain Numerical Rating Scale score from baseline to end of treatment in the nabiximols and placebo groups were 10.7% vs. 4.5% (P = 0.0854) in the intention-to-treat population (primary variable) and 15.5% vs. 6.3% (P = 0.0378) in the per-protocol population. Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at Week 3 and on all three at Week 5. In exploratory post hoc analyses, U.S. patients, but not patients from the rest of the world, experienced significant benefits from nabiximols on multiple secondary endpoints. Possible contributing factors to differences in nabiximols efficacy include: 1) the U.S. participants received lower doses of opioids at baseline than the rest of the world and 2) the subgroups had different distribution of cancer pain types, which may have been related to differences in pathophysiology of pain. The safety profile of nabiximols was consistent with earlier studies. CONCLUSIONS: Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in the U.S. PATIENTS: Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.
Assuntos
Analgésicos/administração & dosagem , Dor do Câncer/tratamento farmacológico , Canabidiol/administração & dosagem , Dor Crônica/tratamento farmacológico , Dronabinol/administração & dosagem , Analgésicos Opioides/administração & dosagem , Quimioterapia Adjuvante , Dor Crônica/etiologia , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Orais , Medição da Dor , Qualidade de Vida , Resultado do TratamentoRESUMO
PURPOSE: Vitamin D inadequacy is a global health concern in athletes as well as the general population. Whilst the role of vitamin D in skeletal health is well defined, there remains uncertainty over whether vitamin D supplementation has an added benefit beyond bone health. METHODS: This randomised placebo-controlled trial in healthy male and female Gaelic footballers (n = 42) investigated the effect of vitamin D3 supplementation [3000 IU (75 µg) daily for 12 weeks, via an oral spray solution] on VO2 max which was the primary outcome measure. Secondary outcomes included skeletal muscle and lung function. RESULTS: Supplementation significantly increased total 25-hydroxyvitamin D concentrations compared to the placebo group (mean ± SD change from baseline, 36.31 ± 32.34 vs. 6.11 ± 23.93 nmol/L, respectively; P = 0.006). At baseline, 50 and 22 % of footballers presented with vitamin D insufficiency (31-49 nmol/L) and deficiency (<30 nmol/L), respectively. Total 25-hydroxyvitamin D concentration did not significantly correlate with any measure of physical performance. Analysis of covariance (ANCOVA) models demonstrated that vitamin D supplementation over 12 weeks had no significant effect on VO2 max (P = 0.375), vertical jump height (P = 0.797), left and right handgrip strength (P = 0.146 and P = 0.266, respectively), forced vital capacity (P = 0.573) or forced expiratory volume at 1 s (P = 0.665), after adjusting for confounders. The high prevalence of vitamin D inadequacy observed in this cohort of collegiate Gaelic footballers supports the need for vitamin D supplementation during wintertime to avoid being at risk of poor bone health. CONCLUSIONS: Twelve-week daily supplementation with 3000 IU (75 µg) vitamin D3 successfully resolved deficiency but did not have any significant effect on VO2 max, skeletal muscle or lung function.
Assuntos
Colecalciferol/administração & dosagem , Suplementos Nutricionais , Futebol Americano , Consumo de Oxigênio , Fenômenos Fisiológicos da Nutrição Esportiva , Deficiência de Vitamina D/tratamento farmacológico , Administração Oral , Adolescente , Atletas , Composição Corporal , Cálcio/sangue , Colecalciferol/sangue , Creatinina/sangue , Método Duplo-Cego , Exercício Físico , Feminino , Força da Mão , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Avaliação Nutricional , Sprays Orais , Cooperação do Paciente , Resultado do Tratamento , Deficiência de Vitamina D/sangue , Adulto JovemRESUMO
Vitamin D inadequacy [total 25(OH)D <50 nmol/L] is widespread in athletes. The biologically active metabolite, 1,25-dihydroxyvitamin D, may be involved in regulating inflammation although in vitro findings have not been consistently replicated in human intervention trials. This study, conducted at a latitude of 55°N, aimed to assess inflammatory biomarkers in Gaelic footballers before and after a wintertime vitamin D3 intervention. Samples from a 12-week double-blind, randomized, placebo-controlled trial, in which 42 Gaelic footballers received 3000 IU (75 µg) vitamin D3 daily or placebo via oral spray solutions, were analysed for a range of inflammatory biomarkers. Cytokines (interleukin-8 and tumor necrosis factor-α), cathelicidin and high sensitivity C-reactive protein were quantified by multiplex assay, enzyme-linked immunosorbent assay and clinical biochemistry, respectively. White blood cell, lymphocyte, and neutrophil concentrations were determined by full blood profile. Data on total 25-hydroxyvitamin D, measured by LC-MS/MS, were available from the previous study. Vitamin D3 supplementation significantly increased mean total 25-hydroxyvitamin D concentrations from 47 to 84 nmol/L (P = 0.006); yet this had no effect on white blood cell count (P = 0.699), lymphocyte (P = 0.694), neutrophil (P = 0.594), interleukin-8 (P = 0.334), tumor necrosis factor-α (P = 0.587), cathelicidin (P = 0.745) or high sensitivity C-reactive protein concentration (P = 0.621) compared to placebo. 12-weeks vitamin D3 supplementation did not impact the immune profile of Gaelic footballers. This is likely because biomarkers were within their respective normal range or at a concentration similar to that of the general population at baseline. Future studies are encouraged to use inflammation as their primary outcome measure and recruit athletes at risk of compromised immunity.
Assuntos
Colecalciferol/administração & dosagem , Inflamação/sangue , Futebol/fisiologia , Peptídeos Catiônicos Antimicrobianos/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Citocinas/sangue , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Interleucina-8/sangue , Contagem de Leucócitos , Masculino , Sprays Orais , Consumo de Oxigênio , Estações do Ano , Fenômenos Fisiológicos da Nutrição Esportiva , Fator de Necrose Tumoral alfa/sangue , Vitamina D/análogos & derivados , Vitamina D/sangue , Adulto Jovem , CatelicidinasRESUMO
BACKGROUND: Delta-9-tetrahydrocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex®) has been recently approved for the management of treatment-resistant multiple sclerosis (MS) spasticity. Although the symptomatic relief of Sativex® on MS-spasticity has been consistently demonstrated, the pathogenetic implications remain unclear and the few electrophysiological studies performed to address this topic yielded controversial results. We therefore aimed to investigate the mechanisms underpinning the modulation of spastic hypertonia by Sativex®, at both central and spinal levels, through an extensive neurophysiological battery in patients with MS. METHODS: Nineteen MS patients with treatment-resistant spasticity were recruited. Before and after 4weeks of treatment with Sativex® patients were clinically assessed with the Modified Ashworth Scale (MAS) and underwent a large neurophysiological protocol targeting measures of excitability and inhibition at both cortical [e.g., intracortical facilitation (ICF), short (SICI) and long (LICI) intracortical inhibition, cortical silent period (CSP)] and spinal level [e.g., H-reflex, H/M ratio and recovery curve of the H-reflex (HRC)]. A group of 19 healthy subjects served as controls. RESULTS: A significant reduction of the MAS score after 4weeks of Sativex® treatment was detected. Before treatment, an increase in the late facilitatory phase of HRC was recorded in patients compared to the control group, that normalised post treatment. At central level, SICI and LICI were significantly higher in patients compared to healthy subjects. After therapy, a significant strengthening of inhibition (e.g. reduced LICI) and a non-significant facilitation (e.g. marginally increased ICF) occurred, suggesting a modulatory effect of Sativex® on different pathways, predominantly of inhibitory type. Sativex® treatment was well tolerated, with only 3 patients complaining about dizziness and bitter taste in their mouth. DISCUSSION: Our results confirm the clinical benefit of Sativex® on spastic hypertonia and demonstrate that it might modulate both cortical and spinal circuits, arguably in terms of both excitation and inhibition. We suggest that the clinical benefit was likely related to a net increase of inhibition at cortical level that, in turn, might have influenced spinal excitability.
Assuntos
Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Fármacos Neuromusculares/administração & dosagem , Extratos Vegetais/administração & dosagem , Adulto , Idoso , Canabidiol , Moduladores de Receptores de Canabinoides/administração & dosagem , Avaliação da Deficiência , Dronabinol , Combinação de Medicamentos , Potencial Evocado Motor/efeitos dos fármacos , Feminino , Seguimentos , Reflexo H/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/fisiopatologia , Espasticidade Muscular/etiologia , Espasticidade Muscular/fisiopatologia , Sprays Nasais , Sprays Orais , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
BACKGROUND: Tetrahydrocannabinol:cannabidiol (THC:CBD) oromucosal spray (Sativex®) is an add-on therapy for moderate-to-severe multiple sclerosis (MS)-related drug-resistant spasticity (MSS). AIM: The MOVE-2 EU study collected data from everyday clinical practice concerning the effectiveness and tolerability of THC:CBD. METHODS: This was an observational, prospective, multicentre, non-interventional study. Patients with resistant MSS prescribed add-on THC:CBD oromucosal spray according to approved labelling, were followed for 3 months. After 1 month, only responders (≥20% improvement in spasticity) continued treatment. The main endpoints were the evolution of MSS and associated symptoms, quality of life (QoL) and tolerability. RESULTS: Four hundred and thirty three patients (55% female) were recruited (98% in Italy). The mean duration of MSS was 7.4 years and baclofen was used by 78.1% of participants. Three hundred and forty nine participants continued with THC:CBD oromucosal spray after 1 month, and 281 after 3 months. THC:CBD mean dosage was 6 sprays/day. MSS scores and spasticity-related symptoms (spasms, fatigue, pain, sleep quality and bladder dysfunction) were significantly improved by THC:CBD at 3 months, as were activities of daily living, and QoL (EQ-5D VAS). Adverse events, none of which were severe or serious, were reported by 10.4% of patients. CONCLUSIONS: In everyday clinical practice, THC:CBD oromucosal spray provided symptomatic relief of MSS and related troublesome symptoms.
Assuntos
Esclerose Múltipla/complicações , Espasticidade Muscular/tratamento farmacológico , Espasticidade Muscular/etiologia , Extratos Vegetais/administração & dosagem , Atividades Cotidianas , Adulto , Baclofeno/uso terapêutico , Canabidiol , Dronabinol , Combinação de Medicamentos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Sprays Orais , Extratos Vegetais/efeitos adversos , Estudos Prospectivos , Qualidade de VidaRESUMO
Vitamin D is typically supplied in capsule form, both in trials and in clinical practice. However, little is known regarding the efficacy of vitamin D administered via oral sprays - a method that primarily bypasses the gastrointestinal absorption route. This study aimed to compare the efficacy of vitamin D3 liquid capsules and oral spray solution in increasing wintertime total 25-hydroxyvitamin D (25(OH)D) concentrations. In this randomised, open-label, cross-over trial, healthy adults (n 22) received 3000 IU (75 µg) vitamin D3 daily for 4 weeks in either capsule or oral spray form. Following a 10-week washout phase, participants received the opposite treatment for a final 4 weeks. Anthropometrics and fasted blood samples were obtained before and after supplementation, with samples analysed for total 25(OH)D, creatinine, intact parathyroid hormone and adjusted Ca concentrations. At baseline, vitamin D sufficiency (total 25(OH)D>50 nmol/l), insufficiency (31-49 nmol/l) and clinical deficiency (<30 nmol/l) were evident in 59, 23 and 18 % of the participants, respectively. Overall, baseline total mean 25(OH)D concentration averaged 59·76 (sd 29·88) nmol/l, representing clinical sufficiency. ANCOVA revealed no significant difference in the mean and standard deviation change from baseline in total 25(OH)D concentrations between oral spray and capsule supplementation methods (26·15 (sd 17·85) v. 30·38 (sd 17·91) nmol/l, respectively; F=1·044, adjusted r 2 0·493, P=0·313). Oral spray vitamin D3 is an equally effective alternative to capsule supplementation in healthy adults.
Assuntos
Colecalciferol/administração & dosagem , Suplementos Nutricionais , Deficiência de Vitamina D/prevenção & controle , 25-Hidroxivitamina D 2/sangue , Adulto , Biomarcadores/sangue , Calcifediol/sangue , Cálcio/sangue , Cápsulas , Colecalciferol/efeitos adversos , Colecalciferol/uso terapêutico , Estudos Cross-Over , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Análise de Intenção de Tratamento , Perda de Seguimento , Masculino , Irlanda do Norte , Sprays Orais , Hormônio Paratireóideo/sangue , Cooperação do Paciente , Estações do Ano , Índice de Gravidade de Doença , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/dietoterapia , Deficiência de Vitamina D/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Topical anesthesia is important for electronic flexible laryngoscopy (EFL) utilization. We hypothesized that oral dyclonine hydrochloride mucilage (ODHM) is superior to tetracaine spray (TS) in patients undergoing EFL examination. METHODS: This study included 932 patients randomized into either an ODHM or TS group, in which patients received either a single utilization of ODHM or TS administered via spray in three intervals. A 4.9 mm diameter flexible PENTAX-VNL-1570STK insertion tube placed into a Naso-Pharyngo-Laryngoscope (PENTAX Medical, Japan) was used in the procedure. Visual analogue scale (VAS) (0-10) was used to evaluate patient tolerance and procedure success by the operator, independently. Procedure time was also recorded. RESULTS: Both patients' and doctors' VAS scores were significantly higher in the ODHM group compared to the TS group. When subgroup analysis was made according to the procedure length (100 s), there was no significant difference in VAS between ODHM and TS groups in the short time procedure (≤100 s), while VAS in the ODHM group was higher compared to the TS in the long time procedure (>100 s), as assessed by both patients and doctors. CONCLUSION: A single use of ODHM seems to be superior to three doses of TS in patients undergoing EFL, specifically in procedures longer than 100seconds.
Assuntos
Anestesia Local/métodos , Laringoscopia/métodos , Manejo da Dor/métodos , Propiofenonas/administração & dosagem , Tetracaína/administração & dosagem , Anestésicos Locais/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Sprays Orais , Medição da Dor , Faringe , Estudos Prospectivos , Método Simples-CegoRESUMO
BACKGROUND: From the time Sativex (THC:CBD) oromucosal spray first became available in European Union countries in 2010 for the management of treatment-resistant multiple sclerosis (MS) spasticity, data from daily practice have been collected through various projects. METHODS: A retrospective registry study and a prospective safety study of THC:CBD oromucosal spray are reported. RESULTS: The most recent analysis of a retrospective registry established in the United Kingdom (UK), Germany and Switzerland, which collected safety data on more than 900 patients, has indicated a positive risk-benefit profile for THC:CBD oromucosal spray during long-term use. Long-term continuation rates were 68% (mean follow-up time 1 year) and the mean dose was 5.4 sprays/day. No new safety concerns were identified, and adverse events of special interest for a cannabis-based medicine were limited. The UK registry has since been closed but remains open in Germany and Switzerland. A prospective safety study undertaken in Spain involved 207 patients from 13 specialized MS centres who had been prescribed THC:CBD oromucosal spray. The findings aligned closely with the UK/German/Swiss registry data in terms of 1-year continuation rates (64.7%), mean daily dose (6.6 sprays/day) and safety profile, including no evidence of addiction, abuse or misuse. CONCLUSIONS: The homogeneity between these observational studies supports the interest in THC:CBD oromucosal spray for management of MS spasticity in daily practice.
Assuntos
Maconha Medicinal/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Sistema de Registros , Acidentes por Quedas , Canabidiol , Depressão/induzido quimicamente , Dronabinol , Combinação de Medicamentos , Alemanha , Humanos , Abuso de Maconha/etiologia , Esclerose Múltipla/complicações , Espasticidade Muscular/etiologia , Sprays Orais , Estudos Prospectivos , Estudos Retrospectivos , Espanha , Suíça , Resultado do Tratamento , Reino UnidoRESUMO
BACKGROUND: The prospective observational MObility ImproVEment (MOVE) 2 study is collecting real-life clinical outcomes data on patients with treatment-resistant multiple sclerosis (MS) spasticity treated with THC:CBD oromucosal spray in routine clinical practice. The MOVE 2 study has been ongoing in Italy, involving more than 30 MS centres across the country, since 2013. METHODS: Web-based real-time data collection techniques are combined with traditional patients' diaries to capture a wide spectrum of outcomes associated with this innovative cannabis-based medication. After surpassing the recruitment threshold of 300 patients, an interim analysis was performed to determine whether the data collected to date align with those from MOVE 2-Germany and the largest phase III randomized controlled trial (RCT) of THC:CBD oromucosal spray. RESULTS: In the Italian cohort, THC:CBD oromucosal spray was added mainly to oral baclofen. Similar to MOVE 2-Germany, during 3 months' observation, treatment discontinuations were limited and patients recorded meaningful improvements on the patient-based 0-10 numerical rating scale and physician-rated modified Ashworth scale at mean daily doses that were about one-third lower than those used in the RCT. Also, similar to MOVE 2-Germany, the proportion of patients reporting adverse events was about one-third of the rate recorded in the RCT. CONCLUSIONS: While MOVE 2-Italy continues, this interim analysis has enabled us to better define the place in therapy of THC:CBD oromucosal spray within the context of daily management of our patients with MS spasticity.
Assuntos
Maconha Medicinal/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Relaxantes Musculares Centrais/uso terapêutico , Espasticidade Muscular/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Adulto , Aminas/uso terapêutico , Baclofeno/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Canabidiol , Estudos de Coortes , Ácidos Cicloexanocarboxílicos/uso terapêutico , Dronabinol , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Gabapentina , Alemanha , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Espasticidade Muscular/etiologia , Estudos Observacionais como Assunto , Sprays Orais , Pregabalina/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Ácido gama-Aminobutírico/uso terapêuticoRESUMO
BACKGROUND: In Italy, all prescriptions for THC:CBD oromucosal spray for treatment of multiple sclerosis (MS) spasticity are linked to the official Agenzia Italiana del Farmaco (AIFA) web-based registry, which tracks the effectiveness and tolerability of medications in a prospective and observational manner. METHODS: AIFA e-registry data for THC:CBD oromucosal spray collected between January 2014 and February 2015 for 1,534 patients from 30 large Italian specialized MS centres were compiled. Patients had a long disease history (17.6 ± 8.6 years) and significant impairment (mean Expanded Disability Status Scale score 6.4 ± 1.2). MS spasticity was evaluated using the 0-10 numerical rating scale (NRS). RESULTS: After the first month titration and trial period, 61.9% of patients achieved sufficient improvement in spasticity (≥20% NRS) to qualify for continued treatment. After 6 months, clinically meaningful ≥30% NRS improvement was recorded in 40.2% of patients continuing with treatment. Spasticity-associated symptoms such as cramps and nocturnal spasms improved in most responding patients. Mean reported doses of THC:CBD oromucosal spray (6.2-6.7 sprays/day) were lower than those reported in clinical trials. Adverse events (mainly mild to moderate) were reported by 15% of patients; no new safety concerns beyond the approved label were identified. CONCLUSION: The results of the AIFA e-registry analysis align with those of other THC:CBD observational projects and reaffirm the characteristics of this therapeutic option in the management of treatment-resistant MS spasticity, a frequently overlooked symptom.
Assuntos
Maconha Medicinal/uso terapêutico , Esclerose Múltipla/tratamento farmacológico , Espasticidade Muscular/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Sistema de Registros , Adulto , Canabidiol , Coleta de Dados , Dronabinol , Combinação de Medicamentos , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Espasticidade Muscular/etiologia , Sprays Orais , Estudos Prospectivos , Resultado do TratamentoRESUMO
The foot and mouth disease virus (FMDV) is sensitive to acids and can be inactivated by exposure to low pH conditions. Spraying animals at risk of infection with suspensions of acid-forming microorganisms has been identified as a potential strategy for preventing FMD. Kombucha is one of the most strongly acid-forming symbiotic probiotics and could thus be an effective agent with which to implement this strategy. Moreover, certain Chinese herbal extracts are known to have broad-spectrum antiviral effects. Chinese herbal kombucha can be prepared by fermenting Chinese herbal extracts with a kombucha culture. Previous studies demonstrated that Chinese herbal kombucha prepared in this way efficiently inhibits FMDV replication in vitro. To assess the inhibitory effects of Chinese herbal kombucha against FMDV in vitro, swine challenged by intramuscular injection with 1000 SID50 of swine FMDV serotype O strain O/China/99 after treatment with Chinese herbal kombucha were partially protected against infection, as demonstrated by a lack of clinical symptoms and qRT-PCR analysis. In a large scale field trial, spraying cattle in an FMD outbreak zone with kombucha protected against infection. Chinese herbal kombucha may be a useful probiotic agent for managing FMD outbreaks.