Sublingual Research Articles

3D Printed Bigel: A Novel Delivery System for Cannabidiol-Rich Hemp Extract

The therapeutic potential of Cannabis sativa L. extract has gained significant attention due to its diverse medical applications. Sublingual administration remains a common delivery method of cannabinoids; however, challenges often arise due to the inconvenient form of the extract and its taste. To address these issues, a novel bigel formulation was developed, combining water and oil phases to enhance stability and bioavailability. This formulation incorporates a cannabidiol-rich hemp extract, hyaluronic acid for its moisturizing properties, and a taste-masking agent to improve patient compliance and comfort. Using a standardized hemp extract rich in cannabinoids and a well-characterized terpene profile, the printability of the bigels was evaluated through 3D printing technology. A printout with known cannabidiol (CBD) and cannabidiolic acid (CBDA) content of 11.613 mg ± 0.192 of CBD and 4.732 mg ± 0.280 of CBDA in the printout was obtained. In addition, the release profile of CBD and CBDA was evaluated to determine the delivery efficiency of the active ingredient—dissolved active ingredient levels ranged from 74.84% ± 0.50 to 80.87% ± 3.20 for CBD and from 80.84 ± 1.33 to 98.31 ± 1.70 for CBDA depending on the formulation. Rheological studies were conducted to evaluate the viscosity of the bigels under varying temperature conditions, ensuring their stability and usability. Findings suggest that this 3D-printed bigel formulation could significantly enhance the delivery of cannabis extracts, offering a more convenient and effective therapeutic option for patients. This research underscores the importance of innovation in cannabinoid therapies and paves the way for further advancements in personalized medicine.

The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children-A pivotal phase III trial.

Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group. Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT-tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS). SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions. This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree pollen-induced AR/C in a paediatric population (5-17 years).

Low-dose sufentanil does not affect tolerance to LBNP-induced central hypovolemia or blood pressure responses during a cold pressor test.

Hemorrhage is a leading cause of death in the prehospital setting. Since trauma-induced pain often accompanies a hemorrhagic insult, the administered pain medication must not interfere with critical autonomic regulation of arterial blood pressure and vital organ perfusion. The purpose of this study was to test two unrelated hypotheses: 1) sublingual sufentanil (Dsuvia) impairs tolerance to progressive central hypovolemia and 2) sublingual sufentanil attenuates pain sensation and the accompanying cardiovascular responses to a noxious stimulus. Twenty-nine adults participated in this double-blinded, randomized, crossover, placebo-controlled trial. After sublingual administration of sufentanil (30 μg) or placebo, participants completed a progressive lower-body negative pressure (LBNP) challenge to tolerance (aim 1). After a recovery period, participants completed a cold pressor test (CPT; aim 2). Addressing the first aim, tolerance to LBNP was not different between trials (P = 0.495). Decreases in systolic blood pressure from baseline to the end of LBNP also did not differ between trials (time P < 0.001, trial P = 0.477, interaction P = 0.587). Finally, increases in heart rate from baseline to the end of LBNP did not differ between trials (time P < 0.001, trial P = 0.626, interaction P = 0.424). Addressing the second aim, sufentanil attenuated perceived pain (P < 0.001) in response to the CPT, though the magnitude of the change in mean blood pressure during the CPT (P = 0.078) was not different between trials. These data demonstrate that sublingual sufentanil does not impair tolerance to progressive central hypovolemia. Additionally, sublingual sufentanil attenuates perceived pain, but not the accompanying mean blood pressure responses to the CPT.NEW & NOTEWORTHY Addressing two unique aims, we observed that sublingual sufentanil administration does not impair tolerance or cardiovascular responses to lower-body negative pressure (LBNP)-induced progressive central hypovolemia. Second, despite pain perception being reduced, sublingual sufentanil did not attenuate mean blood pressure responses to a cold pressor test (CPT).

Combined use of 5-ALA-induced protoporphyrin IX and chlorin e6 for fluorescence diagnostics and photodynamic therapy of skin tumors.

Different types of photosensitizers (PSs) have different dynamics and intensities of accumulation, depending on the type of tumor or different areas within the same tumor. This determines the effectiveness of fluorescence diagnostics and photodynamic therapy (PDT). This paper studies the processes of 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) and chlorin e6 (Ce6) accumulation in the central and border zones of a tumor after combined administration of two PSs into the patient's body. Fluorescence diagnostic methods have shown that sublingual administration of 5-ALA leads to the more intense accumulation of PpIX in a tumor compared to oral administration. Differences have been identified in the dynamics of 5-ALA-induced PpIX and Ce6 accumulation in the central and border zones of the tumor, as well as normal tissues. Ce6 accumulates mainly in the central zone of the tumor while PpIX accumulates in the border zone of the tumor. All patients with combined PDT experienced complete therapeutic pathomorphosis and relapse-free observation.

Cost-utility analysis for sublingual versus intravenous edaravone in the treatment of amyotrophic lateral sclerosis

BackgroundEdaravone has been widely used in amyotrophic lateral sclerosis (ALS) treatment, and a sublingual (SL) tablet has been developed to offer a more convenient alternative for injection. We present a cost-utility analysis to comprehensively evaluate the costs and health outcomes of oral and intravenous edaravone for the treatment of ALS in Chinese medical context.MethodsCost-utility analysis of SL tablets of edaravone versus intravenous edaravone at home was performed by constructing a 20-year Markov model of ALS stage 1–4 and death. The data were extracted from the literature with model assumptions. Typical sensitivity analysis and scenario analysis for administering SL tablets at home versus intravenous tablets at the hospital were performed.ResultsIn the base case analysis, with SL tablets and intravenous injections both at home, the model estimated an additional cost of ¥12,670.04 and an additional 0.034 QALYs over 20 years (life time) of modeling analysis, and the ICER was ¥372,648.24 per QALY. However, in the scenario of intravenous administration at the hospital, SL tablet was demonstrated dominance to intravenous injection.ConclusionsUsing 3 times the GDP per capita of China in 2023 as the threshold, the SL tablet edaravone was not cost-effective in the context of home treatment for both formulationst, but was dominance to intravenous injection in hospital treatment. The results highlighted the importance of treatment context for health economic analysis.

Sublingual β-Glucan/Vitamin C-loaded nanoparticle-embedded polyethylene oxide nanofibrous mats

Nutritional supplements available in various forms provide the consumer with essential molecules demanded for well-being retention. Despite the conveniences provided by oral administration, significant disadvantages such as hepatic first-pass effect, limited absorption, and age-related swallowing problems have been recognized which should be addressed appropriately. Nano-sized biomaterials, which have recently gained popularity in numerous medical fields, have the potential to resolve these problems. In this study, a drug delivery system was designed for sublingual administration and fabricated as β-glucan/vitamin C-loaded chitosan/tripolyphosphate/polyvinylpyrrolidone (CS/TPP/PVP) nanoparticles (DNPs) embedded in polyethylene oxide (PEO) nanofibrous mats (DNFs). The optimum PNP size and DNP size for sublingual administration were obtained as 236 ± 1 nm and 257 ± 1 nm, respectively. The homogenous appearance of DNFs was demonstrated and measured as 783 ± 290 nm using scanning electron microscopy. The synthesized biomaterials were analyzed chemically, 3D-wisely, and thermally. The in vitro drug release kinetics investigation concluded that the sustained drug release of DNP over 15 days proceeded based on the first-order model, and 99.30 % of vitamin C and 99.70 % of β-glucan were released. Neither pure nor drug-loaded samples showed notable cytotoxicity in the 24-h 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay in the L929 cell line. Herein, it has been comprehended that DNF nutritional supplement can be a promising novel supplement dosage form with ease of use, high efficiency, and bioavailability than the conventional methods.

Mannose targeting of poly(lactic-co-glycolic acid): a promising approach for improving sublingual allergen-specific immunotherapy

Objective One of the most effective treatments for allergic respiratory diseases is allergen-specific sublingual immunotherapy (SLIT). While, mannose targeting has been applied in various immunostimulatory approaches, but it has not been investigated in sublingual allergen-specific immunosuppressive treatment. This study assesses mannose targeting for the ovalbumin (Ova) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles(NPs). Methods The emulsion-solvent evaporation method was employed for the synthesis of PLGA NPs containing Ova, and subsequently they attached to D-mannose. Ova-sensitized mice underwent treatment in different ways: subcutaneous administration of 10 µg Ova, sublingual administration of 5 and 10 µg Ova loaded in PLGA NPs, 5 and 10 µg Ova loaded in mannose-targeted PLGA NPs, 10 µg Ova, and 10 µg Ova loaded in dendritic cell-specific aptamer-attached PLGA NPs. Serum Ova-specific IgE and IgG2a levels, as well as IFN-γ, IL-4, IL-10, and IL-17a levels in the supernatant of Ova-stimulated splenocytes were measured. Splenocyte proliferation was assessed using an MTT assay, and also lung histological examinations, and nasal lavage fluid cell counting were performed. Results Ova-specific IgE, IL-4, IL-17a levels, eosinophil cell count, and splenocyte proliferation were remarkably reduced in the mice treated with mannose or aptamer targeted NPs compared to other groups. Also, IL-10 and IFN-γ levels were remarkably increased in the targeted NPs groups. Conclusion Our findings indicated that mannose targeting of PLGA NPs could decrease allergen dose and improve immunomodulatory effects of SLIT. However, this approach suggests an effective formulation for SLIT in the mice model, further studies with common allergens are needed for application in humans.

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)1. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P&amp;lt;0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. 1 Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6):485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

8614 Low Dose Sublingual Estradiol Decreases Protein S, Generating a Potentially Pro-thrombotic Profile: Interim Results of a Controlled Prospective Pilot Study of Treatment-Naïve Trans Women

Abstract Disclosure: S. Bar On: None. I. Yaish: None. M. Barzilai: None. Y. Greenman: None. G. Gindis: None. Y. Moshe: None. K.M. Tordjman: None. Background: Sublingual estradiol (SLE) for gender-affirming hormone therapy (GAHT) of transgender women (TW) might obviate the need for an anti-androgen, and mitigate pro-coagulant changes. We recently showed that 2 mg E, divided into 4 daily sublingual doses, offers no clinical advantage over the same dose given orally in combination with cyproterone acetate (CPA)[1]. Furthermore, we showed that after each sublingual administration, serum estradiol (sE2) peaked to levels, the likes of which are achieved only during induction of ovulation with gonadotrophins. Hypothesis and Aim: Given the exceedingly high peak sE2 measured under SLE-GAHT, we hypothesized it could lead to partial acquired Protein S deficiency, a recognized pro-thrombotic state and risk factor for venous thromboembolic events (VTE). Our aim was to assess the hemostatic system under SLE in comparison with the standard combined oral (CO) approach. Design and Methods: In this ongoing open label study, treatment-naïve TW are assigned in a 1:1 ratio (15 in each arm) to either standard CO (2 mg E2 with 10 mg CPA once daily), or to SLE with 2 mg sublingual estradiol divided into 4 daily dose for 6 months (6M). An extensive battery of hemostatic biomarkers, including free Protein S antigen (fPS), are assessed at baseline (BL) and at 6M. Results: We herein report on 27 subjects (15 CO/12 SLE) who initiated treatment, 17 of whom have already completed it. The median age of the cohort is 20 y (IQR 19-27; range 18-42]. There were no BL differences between the groups. At 6M, none of the hemostatic markers differed between the groups except for fPS, which was significantly lower in the SLE group 79.7%±11.6% vs. 104.6%±5.6%, P=0.039. By paired comparisons for the entire group, fPS decreased from 104%.2±5.2% at BL to 95.8%±5.9% at 6M, P=0.003. This was entirely accounted for by the change in the SLE group, in which fPS went down from 95.7%±10.3% to 79.7%±11.6%, P&amp;lt;0.001; with some values reaching the fPS deficiency range. In contrast, fPS, remained unchanged under CO 108.9%±5.7% and 104.5%±5.2%, at BL and 6M respectively, P=0.153. Conclusions: The most notable interim finding was a clinically significant decrease in fPS under low dose SLE. Given the extreme peaks of sE2 we previously reported with this protocol, an acquired deficiency of this natural anti-coagulant was expected. These preliminary findings support our hypothesis, and raise the concern that GAHT of TW with chronic SLE might carry an increased long-term risk for VTE. [1] Yaish I, Gindis G, Greenman Y, et al. Sublingual Estradiol Offers no Apparent Advantage Over Combined Oral Estradiol and Cyproterone Acetate for Gender-Affirming Hormone Therapy of Treatment-Naive Trans Women: Results of a Prospective Pilot Study. Transgend Health. 2023;8(6): 485-493. Published 2023 Dec 13. doi:10.1089/trgh.2023.0022 Presentation: 6/2/2024

Sublingual route for the continuous release of epinephrine from chitosan nanoparticles

Administration of Epinephrine (Epi) using an intramuscular autoinjector (EAI) is the primary first aid treatment available for the management of anaphylaxis in the community of many countries. Around 1 in 10 patients require a second EAI within 5–15 min. Previously, we successfully developed rapidly disintegrating sublingual tablets (RDST) containing Epi microcrystals that exhibited comparable in vivo pharmacokinetics to that of EAI to overcome the drawbacks of EAIs. To further advance these RDST, we hypothesized that synthesizing Epi nanoparticles (Epi-NP) for incorporation into our previously developed Epi RDST could prolong Epi release sufficiently to eliminate the need for a second dose. Therefore, the primary objective of this research was to synthesize various Epi-NP with different drug loads and investigate their release profiles and sublingual permeability. In vitro release and ex vivo permeability studies were performed using synthetic dialysis membranes and excised porcine sublingual membranes, receptively. The release and permeation of Epi from both NP with adsorbed Epi (Ads Epi-NP) and NP with encapsulated Epi (Enc Epi-NP) were significantly slowed down and achieved continuous control over 8 h. At 60 % Epi load, Epi release from Enc Epi-NP was significantly lower than from Ads Epi-NP, however, the cumulative permeated Epi was only significantly lower towards the end of the experiment, suggesting similar control over Epi permeability. Finally, visualization of NP permeation across the sublayers of the sublingual mucosa confirmed the formation of a temporary depot for Epi and maintained Epi release for several hours post-administration. The results from this study demonstrate for the first time the short-term sustained-release potential of the sublingual route to overcome the need for a second dose.

Sublingual administration of atropine eye drops for treating sialorrhea after stroke: A randomized controlled trial

BackgroundSialorrhea is a common concern in patients with swallowing disorders after stroke. Atropine sulfate blocks the muscarinic receptors in the salivary glands and leads to reduced saliva production. ObjectiveThe present study aimed to assess the safety, efficacy, and tolerability of sublingual administration of atropine eye drops for treating sialorrhea after stroke. DesignThis was a prospective cohort study. SettingThis study was conducted at Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Hubei Province, China. PopulationStroke patients with sialorrhea were analyzed. MethodsOne hundred stroke patients with sialorrhea were randomly assigned to the control group and the test group (n = 50 per group). The control group received routine swallowing rehabilitation training and neuromuscular electrical stimulation. The test group received therapy with 1% atropine eye drops, wherein one drop was administered sublingually 3 times per day. The Sialorrhea Scoring Scale and the incidence of adverse events were used to compare the severity of sialorrhea in the two groups. ResultsThe mean (standard deviation) sialorrhea score improved from 5.12 for the control group with routine rehabilitation training to 3.94 for the test group with atropine eye drop administration (P < 0.01). No significant differences in the incidence of adverse events were observed between the two groups. ConclusionsThe sublingual administration of 1% atropine eye drops three times per day can reduce the degree of sialorrhea to an extent more than that achieved with routine rehabilitation training; thus, this approach is effective, safe, and minimally invasive for treating sialorrhea after stroke.

Sublingual Administration of Tacrolimus is Safe and Provides Similar Drug Exposure to Per-oral Route in Liver Transplant Recipients During Early Postoperative Period–A Large, Retrospective, Observational Study

BackgroundPer-oral(PO) administration of Tacrolimus(TAC) results in inadequate trough levels in early post-operative period in liver-transplant(LT) recipients who undergo Roux-en-Y hepaticojejunostomy for biliary reconstruction. Sublingual administration(SL) of tacrolimus provides an alternative route in such patients. ObjectiveTo assess feasibility and safety of SL tacrolimus in adult LT-recipients in early post-operative period and to compare therapeutic efficacy of SL administration of tacrolimus vs.PO route. Patients and MethodSingle-centre, retrospective, observational study carried out in adult living donor liver transplant(LDLT) recipients between January 2022 till December 2022. Recipients who underwent Roux-en-Y hepaticojejunostomy for biliary reconstruction, received tacrolimus through SL route till post-operative day(POD)5 as they were kept nil per oral constituted the study group while recipients who underwent duct-to-duct(D-D) anastomosis for biliary reconstruction were allowed orally from POD1 and received PO-tacrolimus were chosen as controls. Feasibility and safety of SL-Tacrolimus was assessed in terms of patient acceptance, need to discontinue SL-Tacrolimus, incidence of local adverse effects and systemic adverse events like neurotoxicity and nephrotoxicity. Therapeutic efficacy was evaluated by comparing median trough levels(TAC level) achieved and incidence of graft rejection between two groups. Results212 patients underwent LT during the study period of which 125 were included(58 in SL-group and 67 in PO-group). Both groups had comparable baseline characteristics. In SL-group, all patients tolerated SL-Tacrolimus well and no local adverse events were observed. Patients with SL-Tacrolimus administration achieved higher median TAC level(ng/ml) vs.PO route(5.85 vs 5(p=0.06)) despite similar median cumulative tacrolimus dose before assessing TAC-level. 50% patients achieved TAC level ≥6ng/ml in SL-group vs. 35.8% in PO-group(p=0.14). Incidence of neurotoxicity, nephrotoxicity and graft rejection during hospital stay were similar in both the groups(p=0.56,0.82 and 0.28 respectively). ConclusionSL-tacrolimus is safe and provides similar trough levels to PO-tacrolimus and may be considered as viable alternative whenever inadequate TAC-levels are anticipated through per-oral route.

The Synergistic Combination of Curcumin and Polydatin Improves Temozolomide Efficacy on Glioblastoma Cells.

Glioblastoma (GBL) is one of the more malignant primary brain tumors; it is currently treated by a multimodality strategy including surgery, and radio- and chemotherapy, mainly consisting of temozolomide (TMZ)-based chemotherapy. Tumor relapse often occurs due to the establishment of TMZ resistance, with a patient median survival time of <2 years. The identification of natural molecules with strong anti-tumor activity led to the combination of these compounds with conventional chemotherapeutic agents, developing protocols for integrated anticancer therapies. Curcumin (CUR), resveratrol (RES), and its glucoside polydatin (PLD) are widely employed in the pharmaceutical and nutraceutical fields, and several studies have demonstrated that the combination of these natural products was more cytotoxic than the individual compounds alone against different cancers. Some of us recently demonstrated the synergistic efficacy of the sublingual administration of a new nutraceutical formulation of CUR+PLD in reducing tumor size and improving GBL patient survival. To provide some experimental evidence to reinforce these clinical results, we investigated if pretreatment with a combination of CUR+PLD can improve TMZ cytotoxicity on GBL cells by analyzing the effects on cell cycle, viability, morphology, expression of proteins related to cell proliferation, differentiation, apoptosis or autophagy, and the actin network. Cell viability was assessed using the MTT assay or a CytoSmart cell counter. CalcuSyn software was used to study the CUR+PLD synergism. The morphology was evaluated by optical and scanning electron microscopy, and protein expression was analyzed by Western blot. Flow cytometry was used for the cell cycle, autophagic flux, and apoptosis analyses. The results provide evidence that CUR and PLD, acting in synergy with each other, strongly improve the efficacy of alkylating anti-tumor agents such as TMZ on drug-resistant GBL cells through their ability to affect survival, differentiation, and tumor invasiveness.

Parenteral Buprenorphine for Opioid Withdrawal.

Buprenorphine is the standard of care for treatment of opioid withdrawal. However, when sublingual (SL) administration is not appropriate or practical, parenteral administration by the intravenous (IV) or intramuscular (IM) route may be a reasonable substitute. Although previously used intravenously for the treatment of pain, current practitioners have limited experience with parenteral use of buprenorphine. This is a case series using retrospective chart review of patients at an urban public hospital who received IV or IM buprenorphine for treatment of opioid withdrawal. A query of the electronic health record (EHR) was performed to identify patients who had received IV or IM buprenorphine from January 2020 to December 2021. Charts were reviewed for patient demographics, medical history, substance use history, urine drug screens, clinical scenario, indication for parenteral buprenorphine, dose of buprenorphine, vital sign trends, and any measure of change in withdrawal. Eight patients were identified. The most frequent initial dose of parenteral buprenorphine was 0.3 mg, and if buprenorphine needed to be re-dosed it was most commonly administered every six hours. The most common indications for use were delirium or intractable nausea and vomiting related to opioid withdrawal. Withdrawal improved in 6 of the 8 cases, and often allowed for subsequent use of SL buprenorphine. There were no adverse effects identified. Parenteral buprenorphine was successfully used to treat opioid withdrawal in a select group of patients. Further studies are needed to identify the optimal use parameters of parenteral buprenorphine.

Type I Kounis syndrome in a young woman without chest pain: a case report

BackgroundKounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40–70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain.Case presentationA 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome.ConclusionKounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms.

Sublingual sufentanil tablet system (SSTS) versus a single shot peri-nervous injection of ropivacaine for the management of postoperative pain after total knee arthroplasty: a single-center randomized trial.

For several years, ropivacaine has been the standard-of-care for establishing postoperative femoral nerve block in total knee arthroplasty (TKA) setting and is still widely in use but new approaches such as the patient-controlled administration of sublingual sufentanil tablets system (SSTS) seem to offer good clinical results. Our aim is to compare the SSTS to single shot peri-nervous injection of ropivacaine (single shot) after TKA in terms of effectiveness in pain management and of time to recovery. A total of 165 patients undergoing TKA were enrolled. Eighty-four patients were randomly allocated in the SSTS group and 81 patients in the single shot group. The primary objective of the study was to evaluate performance of Timed Up and Go test. Secondary objectives were to measure the length of stay, NRS pain scale, the adherence to the prescribed plan, the joint mobility, the frequency of rescue analgesic use, side effects and patients' satisfaction. Of all patients of the single shot group, 64 were withdrawn from the study as they unable to achieve pain control; only one patient was withdrawn from the SSTS group. Times for the "Timed Up and Go" test on the 3rd postoperative day were 8.4 ± 1.6 and 11.8 ± 3.6 in the SSTS group (n = 83) and single shot group (n = 17), respectively (p < .001). SSTS provides better pain management when compared to peri-nervous ropivacaine single shot injection after TKA.

Computed tomography angiography assessment of Adamkiewicz artery with sublingual nitroglycerin administration.

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. 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. 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. Nitroglycerin contributed to improving the Adamkiewicz artery's visualization.

Predictors of continuation for asenapine from real-world data in patients with schizophrenia

BackgroundThe continuation rates of pharmacotherapy in schizophrenia exhibit variability, a phenomenon influenced by the specific antipsychotic agent prescribed and patient-related factors such as age and duration of illness. In this context, our study aims to elucidate the predictors of medication continuation for asenapine sublingual tablets, characterized by unique formulation properties.MethodsOur investigation leveraged real-world data collected through post-marketing surveillance in Japan, comprising 3236 cases. Utilizing multivariate logistic regression analysis, we identified patient-related factors associated with medication continuation as the primary outcome measure, subsequently employing survival analysis for further evaluation. Additionally, adverse event occurrence was assessed as a secondary outcome measure.ResultsMultivariate logistic regression analysis unveiled significant predictors of asenapine continuation, notably including patient-related factors such as a chlorpromazine equivalent dose exceeding 600 mg/day and an illness duration of 25 years or more. While the overall continuation rate stood at 40.6%, patients exhibiting factors such as a chlorpromazine equivalent dose surpassing 600 mg/day or an illness duration exceeding 25 years demonstrated continuation rates of 46.3% and 47.9%, respectively. Remarkably, patients presenting both factors showcased the highest continuation rate at 52.5%.ConclusionsOur findings shed light on distinct patient-related predictors of asenapine continuation, deviating from those observed with other antipsychotic medications. This underscores the necessity of recognizing that predictive factors for antipsychotic medication continuation vary across different agents. Moving forward, elucidating these predictive factors for various antipsychotic medications holds paramount importance in schizophrenia treatment, facilitating the delivery of tailored therapeutic interventions for individual patients.

Buprenorphine/naloxone – one formulation that doesn’t fit all: a case report

BackgroundSublingual buprenorphine, approved for treatment of opioid use disorder since 2002, is most commonly available in co-formulation with naloxone. Naloxone is an opioid antagonist minimally absorbed when sublingual (SL) buprenorphine/naloxone is taken as prescribed; it is thought to reduce potential for misuse via intravenous administration. However, growing data and clinical experience demonstrate that previously accepted assumptions about the pharmacokinetics of these medications may not apply to all patients.Case presentationWe present a patient whose adverse post-administration side effects on SL buprenorphine/naloxone resolved with transition to SL buprenorphine monoproduct.DiscussionNaloxone can be detected in nearly all patients taking SL buprenorphine/naloxone, though with apparent variability in clinical effect. In a minority of patients, naloxone can contribute to adverse and potentially treatment-limiting side effects. Furthermore, the naloxone component is commonly misunderstood by patients and providers and can foster mistrust in the therapeutic relationship if providers are perceived to be withholding a more tolerable formulation. Prescribers should have a low threshold to offer buprenorphine alone when clinically appropriate.

Sublingual sufentanil for patient-controlled analgesia during labor induction for pregnancy termination: an effective and well-tolerated approach

BackgroundEffective pain management during labor induction for pregnancy termination is essential. However, to date, no effective treatment has been identified. The primary aim of this study was to measure the analgesic efficacy of a sufentanil sublingual tablet system during pregnancy termination and patient satisfaction by comparing nulliparous and multiparous women. The secondary aims were to characterize the safety profile by reporting any side effects or adverse events and to determine the need for rescue therapy.MethodsWe conducted an observational, retrospective, single-center study involving 48 women. The data retrieved for analysis included the total and hourly doses of sublingual sufentanil, evaluations of pain management satisfaction using a 5-point rating scale (ranging from 1, indicating “not satisfied” to 5, denoting “completely satisfied”), occurrence of side effects and adverse events, and the rate of rescue analgesic use. Categorical and numerical variables were compared between the two groups, and a correlation analysis was performed.ResultsThe median total dose of sufentanil required was 60 mcg. Nulliparous women required a higher dose of sufentanil compared with multiparous women (105 mcg vs. 45 mcg; P = 0.01). Additionally, they underwent a longer labor, indirectly measured by the time of device usage (625 min vs. 165 min; P = 0.05). Regarding satisfaction, 40 patients (83.4%) were satisfied or completely satisfied, whereas only 8 patients (16.6%) reported dissatisfaction. Multiparous women exhibited higher satisfaction levels than did nulliparous women (P = 0.03). No adverse events were reported, and the most common side effects were nausea and vomiting (31.2%). Four patients (12%) required acetaminophen due to insufficient analgesia, with only one patient necessitating a switch to intravenous morphine.ConclusionsSublingual sufentanil was effective in both nulliparous and multiparous women with minimal side effects. Therefore, sublingual sufentanil can be considered a valid strategy for analgesia during labor induction for pregnancy termination.