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BACKGROUND: Circulatory shock and multi-organ failure remain major contributors to morbidity and mortality in critically ill patients and are associated with insufficient oxygen availability in the tissue. Intrinsic mechanisms to improve tissue perfusion, such as up-regulation of functional capillary density (FCD) and red blood cell velocity (RBCv), have been identified as maneuvers to improve oxygen extraction by the tissues; however, their role in circulatory shock and potential use as resuscitation targets remains unknown. To fill this gap, we examined the baseline and maximum recruitable FCD and RBCv in response to a topical nitroglycerin stimulus (FCDNG, RBCvNG) in patients with and without circulatory shock to test whether this may be a method to identify the presence and magnitude of a microcirculatory reserve capacity important for identifying a resuscitation target. METHODS: Sublingual handheld vital microscopy was performed after initial resuscitation in mechanically ventilated patients consecutively admitted to a tertiary medical ICU. FCD and RBCv were quantified using an automated computer vision algorithm (MicroTools). Patients with circulatory shock were retrospectively identified via standardized hemodynamic and clinical criteria and compared to patients without circulatory shock. RESULTS: 54 patients (57 ± 14y, BMI 26.3 ± 4.9 kg/m2, SAPS 56 ± 19, 65% male) were included, 13 of whom presented with circulatory shock. Both groups had similar cardiac index, mean arterial pressure, RBCv, and RBCvNG. Heart rate (p < 0.001), central venous pressure (p = 0.02), lactate (p < 0.001), capillary refill time (p < 0.01), and Mottling score (p < 0.001) were higher in circulatory shock after initial resuscitation, while FCD and FCDNG were 10% lower (16.9 ± 4.2 and 18.9 ± 3.2, p < 0.01; 19.3 ± 3.1 and 21.3 ± 2.9, p = 0.03). Nitroglycerin response was similar in both groups, and circulatory shock patients reached FCDNG similar to baseline FCD found in patients without shock. CONCLUSION: Critically ill patients suffering from circulatory shock were found to present with a lower sublingual FCD. The preserved nitroglycerin response suggests a dysfunction of intrinsic regulation mechanisms to increase the microcirculatory oxygen extraction capacity associated with circulatory shock and identifies a potential resuscitation target. These differences in microcirculatory hemodynamic function between patients with and without circulatory shock were not reflected in blood pressure or cardiac index.

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The current study aimed to evaluate the pharmacokinetics and neuroprotective effect of well-characterised berberine-bovine serum albumin (BBR-BSA) nanoparticles. BBR-BSA nanoparticles were generated by desolvation method. Entrapment efficiency, loading capacity, particle size, polydispersity index, surface morphology, thermal stability, and in-vitro release were estimated. In-vitro pharmacokinetic and tissue distribution were conducted. Their neuroprotection was evaluated against lipopolysaccharides-induced neurodegeneration. BBR-BSA nanoparticles showed satisfactory particle size (202.60 ± 1.20 nm) and entrapment efficiency (57.00 ± 1.56%). Results confirmed the formation of spheroid-thermal stable nanoparticles with a sustained drug release over 48 h. Sublingual and intranasal routes had higher pharmacokinetic plasma profiles than other routes, with Cmax values at 0.75 h (444 ± 77.79 and 259 ± 42.41 ng/mL, respectively). BBR and its metabolite distribution in the liver and kidney were higher than in plasma. Intranasal and sublingual treatment improves antioxidants, proinflammatory, amyloidogenic biomarkers, and brain architecture, protecting the brain. In conclusion, neuroinflammation and neurodegeneration may be prevented by intranasal and sublingual BBR-BSA nanoparticles.

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OBJECTIVE: The purpose of this study was to evaluate the efficacy of sublingual immunotherapy (SLIT) with house dust mite (HDM) on pediatric perennial allergic rhinitis (AR) based on longitudinal assessment of nasal symptoms, laboratory examination, and in vivo biomarkers. METHOD: The subjects included 40 children with perennial AR who had SLIT with HDM for 2 years. Nasal symptoms, medications, skin prick tests, nasal provocation tests, and peripheral blood tests were evaluated before, 6 months, one year and two years after the onset of SLIT. RESULTS: Total nasal symptom scores, prick test wheal diameter, and peripheral blood eosinophil count decreased in 6 months. Total nasal symptom scores continued to decrease from 6 months to 2 years. Symptom-medication scores and nasal provocation test responses decreased in 1 year. Symptom-medication scores continued to decline from 1 to 2 years. Medication scores and nasal eosinophilia decreased in 2 years. Serum specific IgE to HDM slightly increased transiently and decreased in 2 years. The severity of symptoms and specific IgE to HDM at the baseline, and changes of symptoms and specific IgE to HDM during the first six months and first one year of SLIT were correlated with improvement in symptom scores over two years of SLUT. TNSS at baseline was correlated with that at second year. CONCLUSION: Longitudinal assessment of symptoms, allergen specific IgE, and in vivo biomarkers showed the effectiveness of SLIT. Symptom scores and allergen specific IgE may also be early predictive factors of SLIT efficacy in children with AR.

Asunto(s)

Biomarcadores , Inmunoterapia Sublingual , Humanos , Niño , Biomarcadores/sangre , Masculino , Femenino , Estudios Longitudinales , Rinitis Alérgica Perenne/terapia , Rinitis Alérgica Perenne/inmunología , Rinitis Alérgica Perenne/diagnóstico , Pyroglyphidae/inmunología , Animales , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Adolescente , Preescolar

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BACKGROUND: Allergen immunotherapy is the only treatment that can achieve remission for allergic diseases. AIMS/OBJECTIVES: To investigate the three-year adherence to sublingual immunotherapy for Japanese cedar pollinosis and house dust mite allergy at a clinic in Japan and identify factors that influence adherence and severe adverse reactions. MATERIAL AND METHODS: In total, 174 patients aged 12 years or older who started sublingual immunotherapy for Japanese cedar pollinosis (n = 72), house dust mite allergy (n = 55), or both (n = 47) between May 2017 and June 2018. Patient age, sex, type of pharmacotherapy used, adverse reactions, blood test results, and duration of continuous treatment were investigated. RESULTS: The three-year treatment continuation rate was 40.8%. Adverse reaction rates were 12.6% for cedar pollinosis and 40.2% for house dust mite allergy. Patients with dose reductions due to severe reactions had lower first-year continuation rates. In the MITICURE® group, patients with severe reactions had significantly higher serum total IgE levels. Severe reactions were more common in MITICURE® patients with seven or more positive antigen types. CONCLUSIONS AND SIGNIFICANCE: Severe adverse reactions reduced early adherence.

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BACKGROUND: Due to the relative rarity of malignant sublingual gland tumors, diagnosing and treating them clinically pose challenges. Hence, there's a need to explore the pathological types, characteristics, treatment methods, and prognosis of primary malignant tumors of the sublingual gland to improve our understanding and management of these rare yet highly malignant conditions. METHODS: This study reviewed cases of primary malignant sublingual gland tumors, analyzing their characteristics. The treatment methods included surgical excision, with additional radiotherapy, or brachytherapy for advanced stages or positive surgical margins. The study also summarized different treatment approaches, including lymph node dissection and soft tissue reconstruction using free flaps such as the anterolateral thigh flap and forearm flap. RESULTS: We have gathered 23 cases of sublingual gland malignancies treated at the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wuhan University, from January 2013 to May 2024. The most common pathological types were adenoid cystic carcinoma and mucoepidermoid carcinoma, with rare cases of mucosa-associated lymphoid tissue (MALT) lymphoma and nonspecific salivary gland clear cell carcinoma. Early diagnosis and surgical intervention were crucial for a favorable prognosis. Marginal mandibulectomy was necessary for cases involving the mandible. Patients with positive preoperative lymph node detection required cervical lymph node dissection. Extensive tissue defects in the floor of the mouth were effectively reconstructed with free flaps to prevent oral-mandibular fistula. CONCLUSION: Surgical excision remains the preferred treatment for malignant sublingual gland tumors. Early diagnosis and comprehensive surgical management are essential for improving prognosis. The study's limitations include a small sample size and short follow-up duration, necessitating further research with larger clinical samples to confirm these findings.

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Neoplasias de la Glándula Sublingual , Humanos , Femenino , Persona de Mediana Edad , Masculino , Neoplasias de la Glándula Sublingual/patología , Neoplasias de la Glándula Sublingual/terapia , Adulto , Anciano , Pronóstico , Adulto Joven , Escisión del Ganglio Linfático , Carcinoma Adenoide Quístico/terapia , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/cirugía , Carcinoma Adenoide Quístico/diagnóstico , Estudios Retrospectivos , Carcinoma Mucoepidermoide/patología , Carcinoma Mucoepidermoide/cirugía , Carcinoma Mucoepidermoide/terapia , Procedimientos de Cirugía Plástica/métodos

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PURPOSE: The desmopressin daily dose requirement is highly variable among patients with arginine vasopressin (AVP) deficiency (i.e. central diabetes insipidus) and few studies to date have evaluated this topic, with often inconclusive results. The aim of our study was to identify clinical and biochemical predictors of such dose requirements in a cohort of patients with a confirmed diagnosis of permanent AVP deficiency who have good and stable control under substitutive treatment. METHODS: We retrospectively analyzed data of all patients with permanent AVP deficiency undergoing regular follow-up at our Division. Inclusion criteria were the presence of stable disease under therapy for at least 12 months and in good biochemical and clinical control. Patients with AVP deficiency who lacked intact thirst or had a disease duration of less than 12 months were excluded from the analysis. RESULTS: Out of the 132 patients initially screened, 96 patients (M/F 44/52; age 51 [37-63] years) met the inclusion criteria. Patients on nasal spray therapy (n = 8) had a significantly longer disease duration (p = 0.002) than patients treated with oral lyophilizate (n = 88). In the bivariate analysis, considering only patients treated with the sublingual formulation, the drug dose was correlated positively with estimated glomerular filtration rate (eGFR) and weight (r = 0.410, p < 0.001; r = 0.224, p = 0.036, respectively) and negatively with age (r = - 0.433, p < 0.001). In the multivariate regression analysis taking into account age, weight, and eGFR, only age emerged as a significant predictor of the required sublingual desmopressin dose (ß = - 1.426, p = 0.044). CONCLUSION: Our data suggest that patient age appears to be the primary factor associated with the daily sublingual desmopressin dose required to achieve adequate clinical and biochemical control in patients with permanent AVP deficiency.

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BACKGROUND: Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. OBJECTIVE: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. METHODS: We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. RESULTS: Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. CONCLUSIONS: Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

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Alérgenos , Ambrosia , Antígenos de Plantas , Rinitis Alérgica Estacional , Inmunoterapia Sublingual , Humanos , Inmunoterapia Sublingual/métodos , Masculino , Femenino , Estudios Retrospectivos , Rinitis Alérgica Estacional/terapia , Rinitis Alérgica Estacional/inmunología , Adulto , Ambrosia/inmunología , Alérgenos/inmunología , Alérgenos/administración & dosificación , Hungría , Antígenos de Plantas/inmunología , Antígenos de Plantas/administración & dosificación , Persona de Mediana Edad , Adulto Joven , Extractos Vegetales/administración & dosificación , Resultado del Tratamiento , Adolescente , Polen/inmunología

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OBJECTIVE: Asthma is a common chronic condition in children globally. Allergen-specific immunotherapy, such as subcutaneous (SCIT) and sublingual (SLIT) therapies, are promising by increasing allergen tolerance. This meta-analysis compares the efficacy and safety of SLIT and SCIT in pediatric asthma. METHODS: We searched PubMed, Cochrane Library, and Embase for randomized controlled trials and case-control studies comparing SLIT and SCIT in asthmatic children. Meta-analysis was conducted using random-effects models with calculations via R software version 4.3.2 and RevMan version 5.4. Study quality and bias risk were assessed using the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool. RESULTS: The literature search yielded a total of 1787 records, with 7 studies meeting the inclusion criteria after screening and assessments. There was no significant difference in the Total Asthma Symptoms Score between SLIT and SCIT (mean difference -0.05 [95% CI: -0.21; 0.10]). However, asthma improvement rates were higher in the SLIT group (risk ratio 0.77 [95% CI: 0.64; 0.93]). FEV1 improvement showed no significant difference (mean difference -1.60 [95% CI: -6.27; 3.08]). Adverse events were similar between the treatments (risk ratio 0.56 [95% CI: 0.11; 2.82]). CONCLUSIONS: SLIT and SCIT were generally similarly effective and safe for treating pediatric asthma. SLIT may be preferred due to its noninvasive administration. More research is needed on long-term effects and tailored treatment approaches.

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House dust mite (HDM) allergen immunotherapy (AIT) has an established role in the treatment of perennial allergic rhinitis (AR) and allergic asthma (AA) triggered by HDM sensitization. We aimed to identify all double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AR and AA in humans and to summarize the evidence for AIT products that are currently manufactured and available for clinical use. A total of 56 eligible double-blind, randomized, placebo-controlled trials of HDM AIT for the treatment of AA and/or AR in humans fit the inclusion criteria and investigated a total of 14 commercial AIT products; together, the 56 studies enrolled a total of 14,619 patients. Of the 56 studies, 39 studies investigated the current manufacturer-recommended maintenance dose (MRMD) of the product, and 17 investigated other doses. We identified 39 studies (12,539 patients randomized) for 8 sublingual immunotherapy (SLIT) products and 17 studies (2,080 patients randomized) for subcutaneous immunotherapy products. For AR, 3 products, the ALK 12 standardized-quality (SQ-HDM) SLIT tablet, the ALK 6 SQ-HDM tablet, and the SG 300 index of reactivity SLIT tablet, had both dose-finding studies (DFSs) and phase III definitive studies (DSs) to demonstrate efficacy of the MRMD of the product. For AA, 2 products, the ALK 12 SQ-HDM SLIT tablet and the ALK 6 SQ-HDM tablet, had both DFSs and DSs for the MRMD. No subcutaneous immunotherapy product had a paired DFS and DS supporting the MRMD. A total of 30 studies of products no longer commercially manufactured were excluded. This study will help to inform clinical care and product selection for the treatment of HDM-induced AR and AA.

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PURPOSE: Identification of the Adamkiewicz artery before aortic surgery is important for preventing postoperative complications due to spinal cord ischemia. The Adamkiewicz artery is difficult to identify due to its small diameter. Nitroglycerin has a vasodilatory effect and is used clinically to improve visualization of blood vessels on coronary computed tomography (CT) angiography. We investigated whether the vasodilatory effect of nitroglycerin could improve the ability to visualize the Adamkiewicz artery. METHODS: We extracted 33 cases wherein contrast-enhanced CT images were taken before and after aortic aneurysm surgery. Nitroglycerin was administered for coronary artery evaluation on the preoperative CT. However, no nitroglycerin was administered before the postoperative CT. Aortic contrast-to-noise ratio, CT value, image noise, and diameter of the Adamkiewicz artery and anterior spinal artery were measured. The depiction of the Adamkiewicz artery was graded into four grades and evaluated. These measurements were performed by two independent reviewers. RESULTS: In nitroglycerin-administered cases, the contrast-to-noise ratio and CT values were significantly higher (P < 0.001, P < 0.001, respectively); the Adamkiewicz artery and anterior spinal artery diameters were dilated (P = 0.005, P = 0.001, respectively). The Adamkiewicz artery score also improved significantly (P < 0.001). No significant difference was found in image noise. CONCLUSION: Nitroglycerin contributed to improving the Adamkiewicz artery's visualization.

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This review discusses available evidence on the mechanisms of action of bacterial lysates, and the clinical effects of their sublingual administration. Bacterial lysates act through many immunological effects, including dendritic cell activation, modification of circulating lymphocyte subsets and antibody production. The production of salivary IgA was repeatedly shown to be induced by the sublingual administration of a prototype bacterial lysate containing soluble and corpuscular antigens. Bacterial lysates are a useful tool for the prevention of recurrent respiratory tract infections. Sublingual administration should be the preferred option.

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Palisading adenocarcinoma is a morphologically distinct salivary gland neoplasm that has been recently described with predilection to the sublingual gland. We report our experience with this neoplasm to corroborate and enrich the literature and further clarify its phenotype.

Asunto(s)

Adenocarcinoma , Humanos , Adenocarcinoma/patología , Neoplasias de las Glándulas Salivales/patología , Masculino , Persona de Mediana Edad , Femenino , Anciano , Biomarcadores de Tumor/análisis

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The study assessed sublingual fentanyl citrate (SFC) effectiveness and safety for breakthrough cancer pain (BtCP) in older patients. A multicenter, retrospective, observational study was conducted in three subgroups of cancer patients aged over 65 years with BtCP. The reports were collected by 20 oncologists across 12 hospitals. The primary goal was to measure changes in BtCP intensity with SFC treatment over 30 days; secondary objectives included pain relief onset and adverse events. A total of 127 patients with long-term cancer (mean: 3.3 years) were recruited. All of them had BtCP, mostly of mixed origin (62.5%). A significantly lower dose was needed in the high-age group at the final visit compared to baseline (212.90 ± 200.45 mcg vs. 206 ± 167.08 mcg; p = 0.000). Pain intensities at the beginning of the flare and at 30 min after SFC administration were significantly lower when the last and first visits were compared (1.9 vs. 2.3, p = 0.000; and 6.2 vs. 6.8 p = 0.006, respectively). The onset of analgesia was significantly more rapid for half of the patients ≥75 years, compared with 65-69 and 70-74 age groups. SFC appears then to be effective, well-tolerated, and safe to treat BtCP in older cancer patients.

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Introduction: A child's fear of needles may impact the preferred route of allergy immunotherapy (AIT) when choosing between subcutaneous immunotherapy (allergy shots) or sublingual immunotherapy (SLIT). A survey was conducted to understand caregiver health-seeking behavior for children with allergic rhinitis with or without conjunctivitis (AR/C) and explore if fear of needles impacted AIT decisions. Methods: Caregivers of children ages 5-17 years with AR/C were recruited from the Dynata US research panel to participate in an online survey from May-June 2023. The survey received institutional review board exemption status. SLIT-tablets were described as "under-the-tongue tablets". Results: About a third (34%) of surveyed caregivers (n = 437) reported their child had a severe fear of needles and 47% reported moderate fear. Of surveyed caregivers, 53% and 43% reported they had discussed allergy shots and SLIT-tablets, respectively, with their child's physician. SLIT-tablets were preferred by 84% of caregivers; 6% preferred injections and 10% had no preference. Caregivers of children with a severe fear of needles had the highest preference for SLIT-tablets (95%) vs. injections (2%); 85% and 60% of caregivers of children with moderate and low fear, respectively, preferred SLIT-tablets. Among caregivers of children with a severe fear of needles, a higher percentage agreed that their child would welcome taking SLIT-tablets than that their child would accept taking an ongoing series of allergy shots (93% vs. 43%, respectively). Conclusions: Most caregivers preferred SLIT-tablets over allergy shots for their child with AR/C. Preference for SLIT-tablets corresponded with the child's degree of fear of needles. Fear of needles should be included in AIT shared decision-making conversations.

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Allergic rhinitis (AR) is a chronic inflammatory condition of the upper airways caused by a type I hypersensitivity reaction triggered by environmental allergens. AR is associated with significant morbidity and affects patients' quality of life, emotional well-being, productivity, and cognitive functioning. As AR prevalence and morbidity have increased significantly worldwide, similar observations have been noted in the United Arab Emirates (UAE) with AR becoming a potential public health issue. Management of AR in the UAE is mainly provided by non-allergy specialists relying on first-line treatments such as intranasal steroids and antihistamines, with often suboptimal and short-term efficacy. Allergen Immunotherapy (AIT) is the only currently available disease-modifying treatment option in the form of either subcutaneous or sublingual allergen immunotherapy that has been proven to have long-term benefits. This article aims to provide recommendations regarding the use of AIT for managing AR in the UAE, considering both the current landscape in the Emirati healthcare system and local experience.

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RSV infection remains a serious threat to the children all over the world, especially, in the low-middle income countries. Vaccine delivery via the mucosa holds great potential for inducing local immune responses in the respiratory tract. Previously, we reported the development of highly immunogenic RSV virus-like-particles (RSV-VLPs) based on the conformationally stable prefusogenic-F protein (preFg), glycoprotein and matrix protein. Here, to explore whether mucosal delivery of RSV-VLPs is an effective strategy to induce RSV-specific mucosal and systemic immunity, RSV-VLPs were administered via the nasal, sublingual and pulmonary routes to BALB/c mice. The results demonstrate that immunization with the VLPs via the mucosal routes induced minimal mucosal response and yet facilitated modest levels of serum IgG antibodies, enhanced T cell responses and the expression of the lung-homing marker CXCR3 on splenocytes. Immunization with VLPs via all three mucosal routes provided protection against RSV challenge with no signs of RSV induced pathology.

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Anticuerpos Antivirales , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio , Vacunas contra Virus Sincitial Respiratorio , Vacunas de Partículas Similares a Virus , Proteínas Virales de Fusión , Proteínas de la Matriz Viral , Animales , Infecciones por Virus Sincitial Respiratorio/prevención & control , Infecciones por Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/inmunología , Vacunas contra Virus Sincitial Respiratorio/administración & dosificación , Ratones , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Vacunas de Partículas Similares a Virus/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Proteínas Virales de Fusión/inmunología , Proteínas Virales de Fusión/genética , Proteínas Virales de Fusión/administración & dosificación , Femenino , Proteínas de la Matriz Viral/inmunología , Proteínas de la Matriz Viral/administración & dosificación , Proteínas de la Matriz Viral/genética , Inmunidad Mucosa , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Virus Sincitial Respiratorio Humano/inmunología , Pulmón/virología , Pulmón/inmunología , Glicoproteínas/inmunología , Glicoproteínas/administración & dosificación , Administración a través de la Mucosa , Virus Sincitiales Respiratorios/inmunología , Linfocitos T/inmunología

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BACKGROUND AND AIMS: Extended-release naltrexone (XR-NTX) and sublingual buprenorphine (SL-BUP) are both approved for opioid use disorder (OUD) treatment in any medical setting. We aimed to compare the real-world effectiveness of XR-NTX and SL-BUP. DESIGN AND SETTING: This was an observational active comparator, new user cohort study of Medicaid claims records for patients in New Jersey and California, USA, 2016-19. PARTICIPANTS/CASES: The participants were adult Medicaid patients aged 18-64 years who initiated XR-NTX or SL-BUP for maintenance treatment of OUD and did not use medications for OUD in the 90 days before initiation. Our cohort included 1755 XR-NTX and 9886 SL-BUP patients. MEASUREMENTS: We examined two outcomes up to 180 days after medication initiation: (1) composite of medication discontinuation and death and (2) composite of overdose and death. FINDINGS: In adjusted analyses, treatment with XR-NTX was more likely to result in discontinuation or death by the end of follow-up than treatment with SL-BUP: cumulative risk 75.9% [95% confidence interval (CI) = 73.9%, 77.9%] versus 62.2% (95% CI = 61.2%, 63.2%), respectively (risk difference = 13.7 percentage points, 95% CI = 11.4, 16.0). There was minimal difference in the cumulative risk of overdose or death by the end of follow-up: XR-NTX 3.9% (95% CI = 3.0%, 4.8%) versus SL-BUP 3.3% (95% CI = 2.9%, 3.7%); risk difference = 0.5 percentage points, 95% CI = -0.4, 1.5. Results were consistent across sensitivity analyses. CONCLUSIONS: Medicaid patients in California and New Jersey, USA, receiving treatment for opioid use disorder stayed in treatment longer on sublingual buprenorphine than on extended-release naltrexone, but the risk of overdose was similar. Most patients in this study discontinued medication within 6 months, regardless of which medication was initiated.

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BACKGROUND: Traditional treatments for cedar seasonal allergic rhinitis include second-generation antihistamines, nasal corticosteroids, and sublingual immunotherapy (SLIT). Omalizumab (Xolair®), an anti-immunoglobulin E (IgE) monoclonal antibody, is an additional option for severe cases unresponsive to existing therapies. Numerous studies have demonstrated the therapeutic effectiveness of omalizumab for cedar seasonal allergic rhinitis; however, most reported results after only up to four weeks of follow-up. Therefore, this study evaluates the clinical efficacy of omalizumab throughout one whole cedar pollen season.   Subjects and methods: This study included patients from our department and the Otorhinolaryngology Department of Minami Osaka Hospital between 2021 and 2023 who were ≥ 12 years old and had serum total IgE levels of 30-1,500 IU/mL, a baseline weight of 30-150 kg, and persistent severe nasal symptoms despite conventional treatments. Patients taking oral steroids at the time of enrollment or had fewer than two omalizumab doses were excluded. Forty-six patients (26 males, 20 females; mean age, 19.1 ± 11.2 years) met these criteria and received subcutaneous omalizumab every 2 or 4 weeks based on their IgE levels and weight. Symptoms were assessed at baseline and 4, 8, and 12 weeks post-administration using the Total Nasal Symptom Score (TNSS) and the Japanese Standard Quality of Life Questionnaire (JRQLQ No. 1) for allergic rhinitis.   Results: Thirty-six patients were followed up for 8 weeks and 13 for 12 weeks. TNSS significantly improved from 6.6 to 4.5 at 4 weeks, 4.2 at 8 weeks, and 4.1 at 12 weeks (p<0.05). Nasal discharge, sneezing, nasal obstruction, itchy eyes, and tearfulness showed significant improvements (p<0.05). Quality of life scores improved in daily activities, sleep, and physical health from week 4 to week 12.   Discussion: Consistent with previous findings, omalizumab significantly improved nasal and ocular symptoms and quality of life in patients with severe cedar seasonal allergic rhinitis. Despite many patients discontinuing the drug after eight weeks due to high costs, the drug's effectiveness in preventing symptom recurrence suggests potential long-term benefits. Combining omalizumab with SLIT showed no significant differences in outcomes; however, further pharmacoeconomic studies are warranted to evaluate cost-effectiveness.   Conclusion: Omalizumab proved to be an effective treatment for severe cedar seasonal allergic rhinitis, providing significant symptom relief and quality of life improvements. Further studies should investigate its long-term efficacy and safety, including potential adverse effects and the development of anti-omalizumab antibodies.

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Effective sedative drugs are in great demand due to increasing incidence of nervous disorders. The present work was aimed to develop a novel sublingual sedative drug based on glycine and L-tryptophan amino acids. Carbopol and different hydroxypropyl methylcellulose species were alternatively tested as mucoadhesive agents intended to prolong tryptophan sublingual release time. A model lipid medium of fully hydrated L-α-dimyristoylphosphatidylcholine was used for optimal mucoadhesive agents selection. Simultaneous processes of drug release and diffusion in lipid medium were first investigated involving both experimental and theoretical approaches. Individual substances, their selected combinations as well as different drug formulations were consecutively examined. Application of kinetic differential scanning calorimetry method allowed us to reveal a number of specific drug-excipient effects. Lactose was found to essentially facilitate tryptophan release and provide its ability to get into the bloodstream simultaneously with glycine, which is necessary to achieve glycine-tryptophan synergism. Introduction of a mucoadhesive agent into the formulation was shown to change kinetics of drug-membrane interactions variously depending on viscosity grade. Among the mucoadhesive agents, hydroxypropyl methylcellulose species K4M and E4M were shown to further accelerate drug release, therefore they were selected as optimal. Thus, effectiveness of the novel sedative drug was provided by including some excipients, such as lactose and the selected mucoadhesive agent species. A dynamic mathematical model was developed properly describing release and diffusion in lipid medium of various drug substances. Our study clearly showed applicability of a lipid medium to meet challenges such as drug-excipient interactions and optimization of drug formulations.

Asunto(s)

Excipientes , Glicina , Hipnóticos y Sedantes , Triptófano , Triptófano/química , Triptófano/administración & dosificación , Glicina/química , Glicina/administración & dosificación , Administración Sublingual , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/química , Hipnóticos y Sedantes/farmacocinética , Excipientes/química , Liberación de Fármacos , Química Farmacéutica/métodos , Rastreo Diferencial de Calorimetría , Lactosa/química , Derivados de la Hipromelosa/química , Biofarmacia/métodos , Adhesividad , Viscosidad

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Dermoid cysts in the floor of the mouth are a relatively rare and unusual site of location anomalies presumed to be caused by entrapment of germinal epithelium along the lines of embryonic fusion. It presents as soft, non-painful, and slowly growing swelling along the lines of fusion during the closure of mandibular and hyoid branch arches. These cysts are developmental and histopathologically classified into three types: epidermoid, dermoid, and teratoid. We are reporting a rare case of a 32-year-old female who presented in the outpatient department with complaints of painless swelling over the floor of the mouth for two years, suggesting a benign sublingual mass. This case report underscores the importance of clinical presentation, diagnostic workup, and surgical approach in achieving successful outcomes for sublingual mass.