Search

Pre-exposure prophylaxis (PrEP) is highly effective at reducing HIV acquisition. We aimed to estimate usage of oral-PrEP, and factors associated with adherence among female sex workers (FSWs) in Nairobi, Kenya, using a novel point-of-care urine tenofovir lateral flow assay (LFA). The Maisha Fiti study randomly selected FSWs from Sex Worker Outreach Program clinics in Nairobi. Data were collected from 1003 FSWs from June-October 2019, including surveys on self-reported oral-PrEP adherence. Adherence was also measured using the LFA for HIV-negative FSWs currently taking oral-PrEP. Informed by a social-ecological theoretical framework, we used hierarchical multivariable logistic regression models to estimate associations between individual, interpersonal/community, and structural/institutional-level factors and either self-reported or LFA-assessed adherence. Overall, 746 HIV-negative FSWs aged 18-40 participated in the study, of whom 180 (24.1%) self-reported currently taking oral-PrEP. Of these, 56 (31.1%) were adherent to oral-PrEP as measured by LFA. In the multivariable analyses, associations with currently taking oral-PrEP included having completed secondary education, high alcohol/substance use, feeling empowered to use PrEP, current intimate partner, no recent intimate partner violence, having support from sex worker organisations, experiencing sex work-related stigma, and seeking healthcare services despite stigma. Associations with oral-PrEP LFA-measured adherence measured included having only primary education, experience of childhood emotional violence, belonging to a higher wealth tertile, and being nulliparous. Oral-PrEP adherence, measured by self-report or objectively, is low among FSWs in Nairobi. Programs to improve oral-PrEP usage among FSWs should work to mitigate social and structural barriers and involve collaboration between FSWs, healthcare providers and policymakers.

ObjectiveDetermine the prevalence, types, and geographical distribution of oral tumors in dogs in Switzerland to provide insights into demographics, tumor characteristics, and trends.MethodsThe medical and pathology records of dogs diagnosed with oral tumors from 2012 to 2022 were sourced from diagnostic laboratories in Switzerland. The focus was on histopathologically confirmed oral neoplasms. Inflammatory, viral, and cystic lesions were excluded. Geographic trends were analyzed by use of postal addresses, revealing local distributions.ResultsOf the 948 reports, 773 cases fulfilled the study's criteria. Benign tumors constituted 63% (487 of 773), with peripheral odontogenic fibroma being the most common (77.8% [379 of 487]). Among the malignant tumors, malignant melanoma was the most frequent (38.1% [109 of 286]), followed by squamous cell carcinoma (21% [60 of 286]) and fibrosarcoma (8% [23 of 286]). The locations of tumors varied, with a higher prevalence of malignant melanoma on the lips. Histopathologic findings indicated ulceration and necrosis were more common in malignant tumors. Significant differences were noted in the mitotic index between benign and malignant groups. No tumor predisposition was noted for any breed. Oral tumors were prevalent in older dogs (median age, 9.4 years).ConclusionsThe findings highlighted the predominance of benign tumors in dogs in Switzerland, with specific histopathologic features distinguishing benign from malignant cases.Clinical relevanceUnderstanding the prevalence, types, and geographic distribution of oral tumors based on the representation in dogs in Switzerland may aid in early detection, appropriate diagnostic workup, and informed treatment planning for oral tumors in dogs.

Oral broad-spectrum antivirals are urgently needed for the treatment of many emerging and contemporary RNA viruses. We previously synthesized 1-O-octadecyl-2-O-benzyl-sn-glyceryl-P-RVn (ODBG-P-RVn, V2043), a phospholipid prodrug of GS-441524 (remdesivir nucleoside, RVn), and demonstrated its in vivo efficacy in a SARS-CoV-2 mouse model. Structure-activity relationship studies focusing on the prodrug scaffold identified two modifications, 3-fluoro-4-methoxy-benzyl (V2053) and 4-cyano-benzyl (V2067), that significantly enhanced the in vitro broad-spectrum antiviral activity against multiple RNA viruses when compared to V2043. Here, we demonstrate that V2043, V2053, and V2067 are all orally bioavailable, well-tolerated, and achieve high sustained plasma levels after single oral daily dosing. All three phospholipid prodrugs are significantly more active than RVn in vitro and significantly reduce SARS-CoV-2 lung titers in prophylaxis and treatment mouse models of SARS-CoV-2 B.1.351 infection. On a molar basis, V2043 and V2067 are substantially more active than obeldesivir/GS-5245 and molnupiravir in vivo. Together, these data support the continued development of phospholipid RVn prodrugs for the treatment of SARS-CoV-2 and other RNA viruses of clinical concern.

Decision-making in clinical medicine ideally is based upon evidence from randomized, placebo-controlled trials (RCTs) and subsequent systematic reviews and meta-analyses. However, for orphan diseases, the expectation of having one or multiple RCTs that inform clinical guidelines or justify specific treatments can be unrealistic and subsequent therapeutic nihilism can be detrimental to patients. This article discusses the benefits of therapeutic decision-making in the context of orphan diseases, focusing on primary sclerosing cholangitis (PSC) as an example of an orphan disease with poor clinical outcomes. PSC is a rare disorder characterized by inflammation and progressive fibrosis of the bile ducts. It carries a high risk of liver failure, malignancies, and debilitating symptoms that impair quality of life. Liver transplantation is currently the only life-prolonging intervention for PSC, but it is not a curative option. The article highlights the potential benefits of treating PSC patients with oral vancomycin (OV), which has shown significant clinical responses and improved quality of life in some cases. However, access to OV therapy is limited due to the lack of RCTs supporting its use. The standard requirement of having evidence from RCTs may result in withholding potentially life-altering and/or life-saving treatments for patients with orphan diseases. Conducting RCTs is challenging in these patient populations due to difficulties in recruiting the required patient cohorts and limited commercial returns. A standardized adaptive treatment strategy is proposed to address this. This approach leverages the best available evidence for specific treatments, considers individual clinical responses, and adjusts treatment over time.

BACKGROUND: Oral anticoagulants (OACs) are routinely used for the management of atrial fibrillation (AF) while antiplatelet agents are used in coronary artery disease (CAD). However, data regarding the comparative clinical outcomes of OAC monotherapy versus dual antithrombotic therapy (anticoagulant plus antiplatelet agent) in patients with AF and stable CAD are limited. METHODS: A comprehensive search of major databases including PubMed/MEDLINE, Cochrane Library, and Embase was performed from inception to September 1, 2024 to identify randomized control trials (RCTs) that compared OAC monotherapy with dual antithrombotic therapy in patients with AF and stable CAD. The risk ratios (RRs) were estimated with corresponding 95% confidence intervals (CIs) for all outcomes. RESULTS: A total of three RCTs reported data for 3945 patients with AF and stable CAD. The mean age of patients was 73.8 (±11.85) years and the mean follow-up was 22 months. OAC monotherapy was associated with a significantly reduced relative risk of major bleeding (RR: 0.55, 95% CI: 0.32-0.95) compared to dual therapy. The risk of all-cause death (RR: 0.85, 95% CI: 0.49-1.48), cardiovascular death (RR: 0.84, 95% CI: 0.50-1.41), any stroke event (RR: 0.74, 95% CI: 0.46-1.18), and myocardial infarction (RR: 1.57, 95% CI: 0.79-3.12) remained comparable across the two groups. CONCLUSION: OAC monotherapy led to a significant relative risk reduction for major bleeding with similar rates of ischemic events and mortality compared to dual antithrombotic therapy in patients with AF and stable CAD.

BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is a common, yet underdiagnosed, gut condition caused by gut dysbiosis. A previous study has shown the potential of herbal therapy, providing equivalent results to rifaximin. OBJECTIVES: The objective of this study was to assess how the use of an oral botanical regimen may modulate the gut microbiome, facial erythema, and intestinal permeability in those with SIBO. METHODS: This was an open-label prospective study of adults that had lactulose breath test-confirmed SIBO. Participants received a 10-week oral supplementation of a Biocidin liquid tincture and GI Detox+. If participants were found to be non-responsive to treatment after 10 weeks with a persistently positive lactulose breath test, a third oral supplement, Olivirex, was administered for an additional 4 weeks. Lactulose breath tests were administered at baseline, weeks 6, 10, and 14 to assess for SIBO status. A high-resolution photographic analysis system was utilized to analyze changes in facial erythema. Stool sample collections and venipuncture were performed to analyze the gut microbiome and intestinal permeability. RESULTS: A total of 33 subjects were screened with breath testing, and 19 subjects were found to have SIBO. Three of the subjects withdrew during the screening period prior to baseline, and sixteen subjects enrolled. Four subjects dropped out after baseline. Hydrogen-dominant SIBO was the most common subtype of SIBO, followed by methane and hydrogen sulfide. The botanical regimen was most effective for hydrogen- and hydrogen sulfide-dominant SIBO, leading to negative breath test results at week 10 in 42.8% and 66.7% of participants, respectively. Compared to baseline, supplementation with the botanical regimen led to positive shifts in short-chain fatty acid-producing bacteria such as A. muciniphila, F. prausnitzii, C. eutectus, and R. faecis by 31.4%, 35.4%, 24.8%, and 48.7% percent at week 10, respectively. The mean abundance of Firmicutes decreased by 20.2%, Bacteroides increased by 30%, and the F/B ratio decreased by 25.4% at week 10 compared to baseline. At week 10, there was a trending 116% increase in plasma LPS/IgG (p = 0.08). There were no significant changes in plasma zonulin, DAO, histamine, DAO/histamine, LPS/IgG, LPS/IgA, or LPS/IgM. Facial erythema was not statistically different at week 6, but at week 10, there was a 20% decrease (p = 0.001) in redness intensity. Among the patients that extended to week 14, there was no statistical change in erythema. CONCLUSIONS: Supplementation with an antimicrobial botanical supplemental regimen may have therapeutic potential in hydrogen and hydrogen-sulfide subtypes of SIBO. Furthermore, the botanical supplemental regimen may reduce facial erythema, increase SCFA-producing bacteria, decrease the F/B ratio, and modulate markers of intestinal permeability.

Limited estimates exist on risk factors for epithelial ovarian cancer (EOC) in Asian, Hispanic, and Native Hawaiian/Pacific Islander women. Participants in this study included 1734 Asian (n = 785 case and 949 control participants), 266 Native Hawaiian/Pacific Islander (n = 99 case and 167 control participants), 1149 Hispanic (n = 505 case and 644 control participants), and 24 189 White (n = 9981 case and 14 208 control participants) from 11 studies in the Ovarian Cancer Association Consortium. Logistic regression models estimated odds ratios (ORs) and 95% CIs for risk associations by race and ethnicity. Heterogeneity in EOC risk associations by race and ethnicity (P ≤ .02) was observed for oral contraceptive (OC) use, parity, tubal ligation, and smoking. We observed inverse associations with EOC risk for OC use and parity across all groups; associations were strongest in Native Hawaiian/Pacific Islander and Asian women. The inverse association for tubal ligation with risk was most pronounced for Native Hawaiian/Pacific Islander participants (odds ratio (OR) = 0.25; 95% CI, 0.13-0.48) compared with Asian and White participants (OR = 0.68 [95% CI, 0.51-0.90] and OR = 0.78 [95% CI, 0.73-0.85], respectively). Differences in EOC risk factor associations were observed across racial and ethnic groups, which could be due, in part, to varying prevalence of EOC histotypes. Inclusion of greater diversity in future studies is essential to inform prevention strategies. This article is part of a Special Collection on Gynecological Cancers.

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non-opioid, non-NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single-ascending dose (SAD) study and a fed-fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24 mg in healthy volunteers. EC5026 was well tolerated. No treatment-emergent adverse events were considered related to EC5026. No apparent treatment- or dose-related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near-dose-proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5-2 mg doses. Mean half-lives ranged from 41.8 to 59.1 h. for doses of 8-24 mg, supporting a once-daily dosing regimen. In the fed-fasted study using 8 mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half-lives of 59.5 h. in the fed state and 66.9 h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity.

The efficacy of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, on active and stable lesions was evaluated in patients with active non-segmental vitiligo in a phase 2b trial (NCT03715829). Patients were randomized to placebo or daily ritlecitinib 50 mg (with or without 4-week 100-mg or 200-mg loading dose), 30 mg, or 10 mg for 24 weeks. Active lesions showed greater baseline expression of inflammatory/immune markers IFNG and CCL5, levels of CD103, and T-cell infiltrates than stable lesions. Patients with more active than stable vitiligo lesions showed higher baseline serum levels of CXCL9 and PD-L1, while patients with more stable than active lesions showed higher baseline serum levels of HO-1. At Week 24, ritlecitinib 50 mg significantly stabilized mean percent change from baseline in depigmentation extent in both active lesions and stable lesions vs. placebo-response, with stable lesions showing greater repigmentation. After 24 weeks of treatment, ritlecitinib 50 mg increased expression of melanocyte markers in stable lesions, while Th1/Th2-related and co-stimulatory molecules decreased significantly in both stable and active lesions. Serum from patients with more active than stable lesions showed decreased levels of ICOS and NK cell activation markers. These data, confirmed at transcription/protein levels, indicate that stable lesion repigmentation occurs early with ritlecitinib, while active lesions require stabilization of inflammation first. ClinicalTrials.gov: NCT03715829.

PURPOSE OF REVIEW: The aim of this review is to highlight key published oral immunotherapy (OIT) protocols and post-desensitization strategies for the major food allergens and to cover important concepts to consider when evaluating OIT for food-allergic patients. Shared decision-making should help identify patient and family values which will help influence the type of evidence-based protocol and maintenance strategy to use. RECENT FINDINGS: With food OIT emerging as a treatment option, there is a pressing need for patients, physicians, and other providers to have a nuanced understanding of the management choices available to them. There are now randomized controlled trials (RCT) of OIT for peanut, egg, milk, and wheat, and reports of cohorts of patients who have undergone OIT for tree nuts and sesame clinically. The current published protocols contain significant diversity in terms of starting dose, build-up schedule, maintenance dose, and even the product used for desensitization. Emerging data can help direct the long-term maintenance strategy for patients on OIT. Based on patient and family values elicited through the shared decision-making process, an OIT protocol may be selected that balances the level of desensitization, potential side effects, frequency of clinic visits, and potential to induce sustained unresponsiveness, among other factors. Once maintenance dosing is reached, most patients will need to maintain regular exposure to the food allergen to remain desensitized. The option to transition to commercial food products with equivalent amounts of food protein as the OIT maintenance dose would simplify the dosing process and perhaps improve palatability as well. Less frequent or decreased OIT dosing can provide practical benefits but may affect the level of desensitization and safety for some patients.

IntroductionReproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.MethodsParticipants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).ResultsYounger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.DiscussionSeveral aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Objectives: The objectives of this retrospective study were to analyze telehealth utilization for two specialty care practices: oral medicine (OM) and oral and maxillofacial surgery (OMFS) during the first 2 years of the pandemic, its impact as a new treatment modality and on participating providers, as well as identify the type of patient visit that most readily adopted telehealth. Methods: Retrospective study of patients who sought specialty services, OM and OMFS, at an outpatient clinic in a university health system setting between March 1, 2019, and February 28, 2022. Source data were obtained from Epic, an electronic medical record application. Data were graphed using Tableau and Microsoft Excel software. Statistical analysis was performed utilizing chi-squared test and analysis of variance (ANOVA). Results: OMFS utilized telehealth 12% of the time, and OM 8% of the time. The majority (87%) of telehealth visits were for return patients (RPs). Compared with the first year of the pandemic, there was a decrease in the number of telehealth visits in the second year (p = 0.0001). As of August 2022, new patient (NP) telehealth encounters have largely returned to prepandemic levels (0-1.5%), whereas RP telehealth visits remained at an average level of 11.4% (9.4-12.4%). Surveyed providers consider telehealth as an effective complement to in-person care and will continue its use (4.2/5 Likert scale). Conclusions: Telehealth has become a viable pathway of care for OM and OMFS who previously did not utilize the remote platform to deliver healthcare. As a new treatment modality, telehealth is perceived as impactful in increasing access to specialty care by participating providers. NP visits are now almost completely in person, but telehealth continues for RPs. Ongoing demand for telehealth highlights urgency to develop appropriate standards and effective remote diagnostic/monitoring tools to maximize telehealth's capability to leverage finite health care resources and increase access to specialty care.

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) treatment are of interest in oncology due to ease of administration and lack of need for therapeutic monitoring compared to other anticoagulants. Data supporting their use in patients with hematologic malignancies post-hematopoietic stem cell transplant (HCT) are limited. The purpose of the study is to characterize DOAC use in HCT patients. This multicenter, retrospective cohort analysis included allogeneic and autologous HCT recipients. The primary outcome was major bleeding. Secondary outcomes included clinically relevant non-major bleeding (CRNMB)/minor bleeding and VTE recurrence. Of 126 patients, 91 (72.2%) patients received an autologous HCT, and 35 (27.8%) patients received an allo-HCT. No major bleeding occurred in either transplant recipient groups. In autologous HCT recipients, CRNMB/minor bleeding occurred in four (4.4%) patients and VTE recurrence occurred in one (1.1%) patient. For allogeneic HCT recipients, CRNMB/minor bleeding occurred in five (14.3%) patients and VTE recurrence occurred in two (5.7%) patients. For patients that experienced a CRNMB, five (100%) of the allogeneic HCT and two (50%) of the autologous HCT recipients were thrombocytopenic at the time of bleeding. Only 38.5% of patients who experienced a drug-drug interaction requiring DOAC dose adjustment received the appropriate dose adjustment. DOACs were associated with low rates of recurrent VTE and no major bleeding events, similar to published data on DOAC use in the general cancer patient population. This suggests that DOACs may be safe therapeutic options with proactive management of drug interactions and careful monitoring for bleeding events, especially in the allogeneic HCT population where minor bleeding rates were slightly higher.

BACKGROUND: Oral anti-coagulants (OAC) are the intervention for the prevention of stroke, which consistently improve clinical outcomes and survival among patients with atrial fibrillation (AF). The main purpose of this study is to identify problems in OAC utilization among hospitalized patients with AF in China. METHODS: Using data from the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) registry, guideline-recommended OAC use in eligible patients was assessed. RESULTS: A total of 52,530 patients with non-valvular AF were enrolled from February 2015 to December 2019, of whom 38,203 were at a high risk of stroke, 9717 were at a moderate risk, and 4610 were at a low risk. On admission, only 20.0% (6075/30,420) of patients with a diagnosed AF and a high risk of stroke were taking OAC. The use of pre-hospital OAC on admission was associated with a lower risk of new-onset ischemic stroke/transient ischemic attack among the diagnosed AF population (adjusted odds ratio: 0.54, 95% confidence interval: 0.43-0.68; P  70% of AF patients were at a high risk of stroke. Although poor performance on guideline-recommended OAC use was found in this study, over time the CCC-AF project has made progress in stroke prevention in the Chinese AF population.Registration:ClinicalTrials.gov, NCT02309398.

INTRODUCTION: Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. METHODS: Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. RESULTS: The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. DISCUSSION: Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses.

Direct oral anticoagulants (DOACs) exert anticoagulation effect by directly inhibiting Factor Xa (rivaroxaban, apixaban, and edoxaban) or thrombin (dabigatran). Though DOACs are characterized by fixed-dose prescribing and generally do not require routine laboratory drug-level monitoring (DLM), circumstances may arise where the DLM may aid in clinical decision-making, including DOAC dose adjustment, anticoagulant class change, or decisions to withhold or administer reversal agents. We review the current literature that describes high-risk patient groups in which DLM may be beneficial for improved patient anticoagulation management and stewardship. The review also summarizes the limitations of conventional coagulation testing and discuss the emerging utility of quantitative methods for routine and rapid emergent evaluation of DOAC drug levels-in particular, the Anti-Xa activity to detect Factor Xa Inhibitors (rivaroxaban, apixaban, and edoxaban). Both technical and regulatory barriers to widespread DLM implementation are limiting factors to further clinical research that must be overcome, in order to propose universal DOAC DLM strategies and provide clinical-laboratory correlation to formally classify high-risk patient groups.

It is generally believed that bioavailability (F) calculated based on systemic concentration area under the curve (AUC) measurements cannot exceed 1.0, yet some published studies report this inconsistency. We teach and believe, based on differential equation derivations, that rate of absorption has no influence on measured systemic clearance following an oral dose, i.e., determined as available dose divided by AUC. Previously, it was thought that any difference in calculating F from urine data versus that from systemic concentration AUC data was due to the inability to accurately measure urine data. A PubMed literature search for drugs exhibiting F > 1.0 and studies for which F was measured using both AUC and urinary excretion dose-corrected analyses yielded data for 35 drugs. We show and explain, using Kirchhoff's Laws, that these universally held concepts concerning bioavailability may not be valid in all situations. Bioavailability, determined using systemic concentration measurements, for many drugs may be overestimated since AUC reflects not only systemic elimination but also absorption rate characteristics, which is most easily seen for renal clearance measures. Clearance of drug from the absorption site must be significantly greater than clearance following an iv bolus dose for F(AUC) to correctly correspond with F(urine). The primary purpose of this paper is to demonstrate that studies resulting in F > 1.0 and/or greater systemic vs urine bioavailability predictions may be accurate. Importantly, these explications have no significant impact on current regulatory guidance for bioequivalence testing, nor on the use of exposure (AUC) measures in making drug dosing decisions.

Background: This study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM. Methods: This study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels. Results: The MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes. Conclusion: The study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions. [ABSTRACT FROM AUTHOR]

The article discusses the potential role of colchicine in treating Oral Mucous Membrane Pemphigoid (MMP), an autoimmune disease affecting the oral cavity. While corticosteroids are the first-line treatment, colchicine showed promising results in patients resistant to other therapies. A retrospective study at Bordeaux University Hospital found that colchicine led to remission in oral MMP lesions, with fewer adverse effects compared to dapsone. Further research is needed to confirm these findings and establish colchicine as a viable second-line treatment option for MMP. [Extracted from the article]

Oral hygiene is an important self‐care skill that some children may lack, especially children with autism spectrum disorder (ASD). Although some studies have evaluated procedures for teaching toothbrushing, no previous studies have demonstrated procedures for teaching flossing, which is essential for oral hygiene. This study evaluated an intervention for teaching water flossing to two children with ASD and two children without an ASD diagnosis. The intervention package included backward chaining, video modeling, and reinforcement, with some components implemented by a caregiver and some components implemented by an experimenter via telehealth. Behavioral skills training was used to train caregivers prior to implementation of the study. Results indicated that the intervention package was effective in teaching all participants to independently floss their teeth with a water flosser. Effects maintained for all participants 1‐week after completion of teaching. Questionnaires given to caregivers, participants, and dental professionals indicated high social validity. [ABSTRACT FROM AUTHOR]

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients. [ABSTRACT FROM AUTHOR]

Background Fosfomycin is an antibiotic extensively used to treat uncomplicated urinary tract infections in women, and it is available in different salts and formulations. The European Medicines Agency (EMA) recommends further studies to characterize the pharmacokinetics of fosfomycin calcium for oral administration and to justify its dosage recommendation. Objectives A population pharmacokinetic model of fosfomycin calcium was developed after oral administration to healthy women. Methods A clinical trial (a randomized, open-label, bioavailability study of single and multiple doses of 1000 mg capsules, single dose of 500 mg capsule and single dose of 250 mg/5 mL suspension of oral fosfomycin calcium under fasted conditions in healthy women volunteers, Code: PD7522.22, EudraCT: 2020-001664-28) was carried out at the Clinical Trial Unit, Araba University Hospital (Vitoria-Gasteiz, Spain). Twenty-four healthy women were included in the study, and plasma samples were collected at different times over a period of 24 h. The concentration–time data of fosfomycin in plasma were modelled by a population approach using a nonlinear mixed-effects modelling implemented by NONMEM 7.4 (ICON Clinical Research LLC, North Wales, PA, USA). Results The pharmacokinetics of fosfomycin was best described by a two-compartment model. Creatinine clearance and body weight were identified as covariates for fosfomycin clearance and volume of distribution, respectively. Conclusions This study provides relevant information on the pharmacokinetic profile of fosfomycin in women after oral administration as calcium salt. This population model may be very useful for establishing dosage recommendations of fosfomycin calcium to treat urinary tract infections in women. [ABSTRACT FROM AUTHOR]

Adherence and treatment continuation rates of the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) semaglutide for both oral (O‐SEMA) and subcutaneous injection (SEMA‐SC) remain unknown in real‐world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O‐SEMA and once‐weekly SEMA‐SC in patients with type 2 diabetes using a real‐world claims database. SEMA‐SC initiators were 1:1 propensity score‐matched to O‐SEMA initiators. Non‐adherence was defined as <0.8 of the proportion of days covered. SEMA‐SC had a significantly higher odds ratio (OR) for non‐adherence than O‐SEMA (OR: 1.39). The hazard ratio for treatment discontinuation, using O‐SEMA as the reference, was 1.45 for SEMA‐SC, although the discontinuation rate of O‐SEMA was higher during the early stage. O‐SEMA initiators showed significantly higher adherence and greater persistence in therapy than SEMA‐SC initiators at 12 months, which could lead to earlier initiation of GLP‐1RA treatment. [ABSTRACT FROM AUTHOR]

Objective: Diagnosing lesions with unusual clinical presentation can be challenging, mostly for cases in which the inclusion of oral metastasis in the differential diagnosis is necessary. Materials and Methods: A 55‐year‐old man complaining of a large mass in the oral cavity was referred to the Hospital Dentistry Service. The patient reported bleeding episodes and pain, with a 5‐month evolution. Intraoral examination revealed a 5 cm tumour with purplish‐red and ulcerated focal areas at the right buccal mucosa. Differential diagnosis included malignant mesenchymal tumours, lymphoproliferative lesions, and metastasis of an occult primary lesion. Two biopsies were conducted, with the first one presenting an intense haemorrhage, and the second performed under general anaesthesia and difficult bleeding control. Results: Histologic and immunohistochemical analysis diagnosed a clear cell carcinoma infiltration. A whole‐body CT scan reveals a renal tumour with multiple metastasis sites in the abdomen and bones. Metastatic clear cell renal cell carcinoma was finally confirmed, and the patient was followed with palliative care for 4 months. Conclusion: A challenging diagnosis of a rare metastatic lesion in the oral cavity was conducted after two procedures under difficult bleeding conditions. [ABSTRACT FROM AUTHOR]

Background: Cyclosporine A (CsA) is used as a steroid-sparing or alternative immunosuppressing agent in cats with various immune-mediated diseases such as immune-mediated hemolytic anemia. Daily treatment dosages of 5–20  mg/ kg have been described. Interindividual variations in CsA blood levels are known to occur. To determine when steady-state conditions are reached and thus the earliest advisable time for monitoring CsA blood levels during the course of treatment, a prospective experimental study was conducted in six healthy adult Domestic Shorthair cats. Materials and methods: Cats were treated with an oral dosage of 7  mg/kg CsA q 12  h for 10  days. On days 1, 2, 3, 5, 7, and 10 after the start of CsA administration (i.e., after 1, 3, 5, 9, 13, and 19 CsA administrations), EDTA blood was collected to measure the CsA level 12  h after the CsA administration (trough values) using high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS/MS). Results: Statistical analysis revealed a significant increase in mean CsA blood levels up to day 5 (2,050  ±  964.2  ng/mL [mean  ±  SD], 832–3,203  ng/mL [minimum–maximum]; repeated-measures ANOVA: p  =  0.0021), while values on days 5 and 7 did not differ significantly from CsA concentrations on day 10. CsA concentrations showed markedly interindividual variability. Conclusion: Cyclosporine A blood levels reached a steady state on day 5 of high dosages of CsA q 12  h (i.e., after nine CsA administrations), indicating that this time point is suitable for monitoring blood levels in clinical patients. Results confirmed the well-known remarkable interindividual variability of CsA, indicating the need for treatment monitoring. The assessed treatment regime resulted in significantly higher mean CsA trough levels than the target range for immunosuppressive therapy (200–600  ng/mL). [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Design Setting Population Methods Main Outcome Measures Results Conclusions To identify a microbial signature for endometriosis for use as a diagnostic non‐invasive biomarker.Prospective cohort pilot study.Nepean Hospital and UNSW Microbiome Research Centre, Australia.Sixty‐four age‐ and sex‐matched subjects (n = 19 healthy control (HC); n = 24 non‐endometriosis (N‐ENDO) and n = 21 confirmed endometriosis (ENDO)). All study participants, besides healthy controls, underwent laparoscopic surgical assessment for endometriosis, and histology was performed on excised lesions.Oral, stool and, vaginal samples were self‐collected at a single time point for healthy controls, and preoperatively for patients undergoing laparoscopy. Samples underwent 16S rRNA amplicon sequencing, followed by bioinformatics analysis.Compositional differences between cohorts as identified by diversity analyses, and differentially abundant microbial taxa, as identified by LEfSE analysis.The composition of the oral (adjusted p = 0.003), and stool (adjusted p = 0.042) microbiota is different between the three cohorts. Differentially abundant taxa are present within each cohort as identified by LEfSE analysis. Particularly, Fusobacterium was enriched in the oral samples of patients with moderate/severe endometriosis.Taxonomic and compositional differences were found between the microbiota in the mouth, gut and, vagina of patients with and without endometriosis and healthy controls. Fusobacterium was enriched in patients with moderate/severe endometriosis. Fusobacterium is noted as a key pathogen in periodontal disease, a common comorbidity in endometriosis. These findings suggest a role for the oral, stool and, vaginal microbiome in endometriosis, and present potential for microbial‐based treatments and the design of a diagnostic swab. [ABSTRACT FROM AUTHOR]

Nanoemulsions (NEs) are submicron-sized heterogeneous biphasic liquid systems stabilized by surfactants. They are physically transparent or translucent, optically isotropic, and kinetically stable, with droplet sizes ranging from 20 to 500 nm. Their unique properties, such as high surface area, small droplet size, enhanced bioavailability, excellent physical stability, and rapid digestibility, make them ideal for encapsulating various active substances. This review focuses on recent advancements, future prospects, and challenges in the field of NEs, particularly in oral, parenteral, and ophthalmic delivery. It also discusses recent clinical trials and patents. Different types of in vitro and in vivo NE characterization techniques are summarized. High-energy and low-energy preparation methods are briefly described with diagrams. Formulation considerations and commonly used excipients for oral, ocular, and ophthalmic drug delivery are presented. The review emphasizes the need for new functional excipients to improve the permeation of large molecular weight unstable proteins, oligonucleotides, and hydrophilic drugs to advance drug delivery rapidly. [ABSTRACT FROM AUTHOR]

Objective: To examine the content of Instagram posts about oral cancer and assess its usefulness in promoting oral cancer awareness and early detection practices. Methods: A systematic search of Instagram for posts about oral (mouth) cancer was conducted using the hashtags #oral cancer and #mouth cancer. Posts usefulness in promoting awareness and early detection was assessed using the early detection usefulness score, and caption readability was assessed using the Flesch Kincaid readability score. Results: A total of 81,000 posts were identified, and 200 posts were thoroughly evaluated. Included posts gathered a total of 48,118 (mean = 420.59 likes) and 27,898 views. Most posts (81.5%) were educational to the lay person, and India and the UK were the major contributors. The most discussed topics were prevention and early detection (55%). Representative clinical images were present in 35.5% of posts. Only 9.5% of posts mentioned the source of information, and the mean usefulness score was only 2.1 out of 10. The mean reading ease score was 56.7 ± 43.8 (range from 1 to 98 out of 100). Conclusion: Instagram shows potential for promoting oral cancer awareness, particularly in prevention and early detection. However, concerns regarding content quality, scientific validity, and clarity persist. [ABSTRACT FROM AUTHOR]

Myiasis is a disease caused by fly larvae from the Diptera order settling in various tissues and organs of humans or animals. To report the diagnosis of myiasis larvae invading the oral and nasal cavities of patients in the management of intensive care units and to draw attention to the poor hygiene situation. A 78-year-old male patient diagnosed with cancer and a 93-year-old male patient diagnosed with ischemic cerebrovascular disease were followed up in the intensive care unit. On the 21st day of the cancer patient's hospitalization, eight larvae were removed from the oral cavity. In the first month of the other patient's hospitalization, six larvae were seen in the patient's nasal osteum near the feeding tube. A clinical diagnosis of myiasis was made and the larvae were initially manually removed for treatment, followed by medication. In conclusion, myiasis is a rare condition, but good hygiene, correct diagnosis, and treatment are necessary to prevent further harm to those who have risk factors such as immunosuppression, poor hygiene, malnutrition, diabetes, and peripheral vascular disease, particularly those who are hospitalized. [ABSTRACT FROM AUTHOR]

Objectives: Sedation before veterinary visits is advocated to help reduce fear and anxiety in cats and facilitate safe handling. The aim of this study was to evaluate the effectiveness of trazodone, gabapentin and a trazodone/gabapentin combination for oral sedation in healthy feline patients before blood donation. Methods: A total of 21 cats were included in the study. Baseline sedation scores were obtained, and cats were randomly assigned to receive oral trazodone at 5 mg/kg (T), oral gabapentin at 10 mg/kg (G), their combination (TG) or placebo (control group). A sedation score was obtained 1 h after drug administration. A blood sample was obtained at the time of blood collection for quantification of drug plasma concentrations. Agreement between observers was tested with a Cohen's Kappa test. Sign tests to compare change within treatment and a Skilling–Mack rank ANOVA to test for differences between groups were performed to compare pre- and post-sedation scores as well as a magnitude of differences over time between the groups. A Spearman's rank correlation coefficient test was used to correlate sedation scores with drug plasma concentrations. Results: Post-sedation final scores were significantly higher only in the T (P = 0.022) and TG groups (P <0.001). The magnitude of change between pre- and post-sedation scores was larger in the TG (P <0.0032) and T groups (P <0.038) compared with the control group. There were no other significant differences between the groups. There was no correlation between drug plasma concentrations and sedation scores in any of the groups. Conclusions and relevance: Administration of oral trazodone alone at 5 mg/kg or in combination with gabapentin at 10 mg/kg resulted in significant sedation in healthy cats with no evident side effects. The degree of sedation was more profound when both drugs were combined, but a gabapentin dose of 10 mg/kg alone failed to provide significant sedation in this population. [ABSTRACT FROM AUTHOR]

Introduction: Morphine is an effective analgesic in horses, however, IV administration at therapeutic doses has been shown to produce dose-dependent neuroexcitation and unwanted gastrointestinal effects. The analgesic effects of morphine have, at least in part, been attributed to the morphine-6-glucuronide (M6G) metabolite. Oral administration to horses results in comparable M6G concentrations to that achieved following IV administration of a therapeutic dose without the adverse effects. The anti-nociceptive effects have not yet been reported. In the current study the thermal anti-nociceptive effects of single and multiple oral doses of morphine were assessed. Methods: Six horses received a single 0.2 mg/kg IV dose of morphine and multiple oral doses of 0.8 mg/kg morphine every 12 h for 4.5 days. Blood samples were collected throughout administration, morphine, and metabolite concentrations determined and pharmacokinetic analysis performed. Drug related behavior and physiologic responses were recorded. Response to noxious stimuli was evaluated by determining thermal threshold latency in response to the application of heat. Results: The maximum concentrations of M6G were higher following oral administration compared to IV and the combined morphine and M6G concentrations exceeded that of IV administration starting at 2 h. Oral administration of 0.8 mg/kg morphine provided and maintained comparable anti-nociception effects to IV morphine with less adverse effects, following single and multiple doses. Morphine was well tolerated following oral administration with less excitation and minimal effects on gastrointestinal borborygmi scores compared to IV administration. Discussion: Results of the current study warrant further investigation of the anti-nociceptive effects of oral morphine administration to horses. [ABSTRACT FROM AUTHOR]

Background: The new frontiers of computer-based surgery, technology, and material advances, have allowed for customized 3D printed manufacturing to become widespread in guided bone regeneration (GBR) in oral implantology. The shape, structural, mechanical, and biological manufacturing characteristics achieved through 3D printing technologies allow for the customization of implant-prosthetic rehabilitations and GBR procedures according to patient-specific needs, reducing complications and surgery time. Therefore, the present narrative review aims to elucidate the 3D-printing digital radiographic process, materials, indications, 3D printed manufacturing-controlled characteristics, histological findings, complications, patient-reported outcomes, and short- and long-term clinical considerations of customized 3D printed mesh, membranes, bone substitutes, and dental implants applied to GBR in oral implantology. Methods: An electronic search was performed through MEDLINE/PubMed, Scopus, BioMed Central, and Web of Science until 30 June 2024. Results: Three-dimensionally printed titanium meshes and bone substitutes registered successful outcomes in vertical/horizontal bone defect regeneration. Three-dimensionally printed polymeric membranes could link the advantages of conventional resorbable and non-resorbable membranes. Few data on customized 3D printed dental implants and abutments are available, but in vitro and animal studies have shown new promising designs that could improve their mechanical properties and tribocorrosion-associated complications. Conclusions: While 3D printing technology has demonstrated potential in GBR, additional human studies are needed to evaluate the short- and long-term follow-up of peri-implant bone levels and volumes following prosthetic functional loading. [ABSTRACT FROM AUTHOR]

Calcifying odontogenic cyst, also known as Gorlin cyst is a rare benign cystic lesion primarily found in the jawbones, accounting less than 1% of odontogenic cysts. It can be associated with odontogenic tumors such as odontomas. We report a rare case of COC associated with complex odontoma in a young patient and discuss its clinical features, diagnosis, and treatment options. An 18-year-old female patient presented with a painless radiopaque lesion of the right mandibular bone at Oral Medicine and Oral Surgery department. Radiographs revealed irregular tooth-like structures in the canine-premolar area. The lesion was surgically removed, and histopathology confirmed COC with a complex odontoma. As of the World Health Organization's 2022 definition, COC is a developmental odontogenic cyst characterized by calcified ghost cells. It typically affects individuals during their second and third decades of life, with no gender preference, almost equally in the maxilla and the mandible. The main treatment is total enucleation, with a generally favorable prognosis. Histopathology is essential for diagnosis due to its mimicry of other jaw conditions. Long-term follow-up is needed to prevent recurrences. [ABSTRACT FROM AUTHOR]

Clonazepam causes sedation and psychomotor impairment in people. Due to similarities between people and swine in response to benzodiazepines, clonazepam may represent a viable option to produce mild‐to‐moderate tranquillization in pigs. The objective of this study was to determine the pharmacokinetic profile of a single oral dose (0.5 mg/kg) of clonazepam in eight healthy, growing commercial cross pigs. Serial plasma samples were collected at baseline and up to 96 h after administration. Plasma concentrations were quantified using reverse‐phase high‐performance liquid chromatography, and compartment models were fit to time–concentration data. A one‐compartment first‐order model best fits the data. Maximum plasma concentration was 99.5 ng/mL, and time to maximum concentration was 3.4 h. Elimination half‐life was 7.3 h, mean residence time 7.4 h, and apparent volume of distribution 5.7 L/kg. Achieved plasma concentrations exceeded those associated with psychomotor impairment in people although pharmacodynamic effects have not been investigated in pigs. A simulated oral regimen consisting of 0.35 mg/kg administered every 8 h to pigs would achieve plasma concentrations above 32 ng/mL which are shown to produce psychomotor impairment in people. Further studies to test the clinical efficacy of these dosages in commercial and miniature pigs are warranted. [ABSTRACT FROM AUTHOR]

Oral lichen planus is a frequent, chronic autoimmune disease that affects the oral mucosa and is characterized as an oral potentially malignant disorder. The aim of our study is to examine the presence of CSCs bearing CD147 (a marker related to local inflammation and associated with various cancers) through immunohistochemistry in oral lichen planus (OLP) compared to oral leukoplakia (OL) and healthy tissues. These findings could contribute to clinical practice by providing a marker for the prognostic assessment of OLP lesions with regards to their potentially malignant nature. The study sample consisted of paraffin-embedded oral mucosa specimens from the archives of the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece during the period 2009–2019. The study sample contained 24 cases of OLP (14 erosive and 10 reticular) and 30 cases of oral leukoplakia, which were compared to 5 normal oral epithelium samples derived from healthy epithelium adjacent to fibromas from other cases. Cell membrane staining of CD147 was observed mostly in the basal and parabasal cell layer. The statistically significantly higher expression of CD147 in the erosive lichen planus subgroup than in the moderately and severely dysplastic leukoplakia subgroup (p = 0.01) constituted the most important finding of this study. The characteristic expression of CD147 in erosive OLP suggests the presence of epithelial cells with CSC characteristics, but its lower expression in oral leukoplakias suggests a more intense relation of the CD147 marker with inflammation rather than with oral dysplastic progression. [ABSTRACT FROM AUTHOR]

Background: Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, debilitating episodes of submucosal and/or subcutaneous tissue swelling, which may be life‐threatening depending on anatomic location. The two primary management strategies for HAE are ready access to effective on‐demand treatment in all patients and the prevention of attacks (short‐term prophylaxis [STP] and long‐term prophylaxis [LTP]) in appropriate patients. All approved on‐demand and most LTP medications require subcutaneous or intravenous administration. Injection‐related challenges include trypanophobia (fear of needles), difficulty with self‐administration, injection‐site reactions (e.g., pain, erythema, bleeding, bruising), and anxiety—all contributing to poor compliance and administration delays. Oral HAE treatments may improve outcomes by reducing treatment barriers. Aim: To review oral therapies, approved or in development, for on‐demand treatment and/or prevention of HAE attacks. Materials and Methods: To provide a comprehensive review, data was obtained from publicly available resources through a targeted PubMed literature review and supplemented by information provided on company websites (search cutoff of May 31, 2024). Results: Berotralstat, an oral plasma kallikrein (PKa) inhibitor, is approved for LTP. Sebetralstat, another PKa inhibitor, is the investigational first oral on‐demand HAE treatment to complete a phase 3 trial. Deucrictibant, an oral bradykinin B2 receptor antagonist, has completed phase 2 trials for on‐demand therapy and LTP. Several other oral PKa inhibitors (ATN249, VE‐4666, and VE‐4062) are in early development for LTP. Conclusion: Substantial advances have been made in the development of oral treatments for HAE. These treatments have the potential to improve and optimize clinical outcomes, satisfaction, and quality of life among patients with HAE. [ABSTRACT FROM AUTHOR]

3D printing technologies confer an unparalleled degree of control over the material distribution on the structures they produce, which has led them to become an extremely attractive research topic in pharmaceutical dosage form development, especially for the design of personalized treatments. With fine tuning in material selection and careful design, these technologies allow to tailor not only the amount of drug administered but the biopharmaceutical behaviour of the dosage forms as well. While fused deposition modelling (FDM) is still the most studied 3D printing technology in this area, others are gaining more relevance, which has led to many new and exciting dosage forms developed during 2022 and 2023. Considering that these technologies, in time, will join the current manufacturing methods and with the ever-increasing knowledge on this topic, our review aims to explore the advantages and limitations of 3D printing technologies employed in the design and development of pharmaceutical oral dosage forms, giving special focus to the most important aspects governing the resulting drug release profiles. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction Information from published studies describing dental treatment of nonmilitary personnel in a military theater of operations is sparse. The primary objective of this study is to determine the number of dental emergencies (DEs) and the types of dental treatment rendered on non-U.S. military (civilian) personnel treated by Navy dentists in 2007-2008 in Iraq and 2009 in Afghanistan. The second objective is to compare the type of DE treatment procedures provided to civilian personnel to the type of DE treatment procedures performed on U.S. military personnel. Materials and Methods Navy Dental Officers documented the diagnoses of unscheduled DEs. All treatment provided was described at the time of treatment using the Current Dental Terminology codes of the American Dental Association. Current Dental Terminology Code A0145 (2007 and earlier) and A0199 (2008 onward) in the patient encounter indicated a DE. This study is limited to DE occurring in (1) patient categories: U.S. civilian employees, other beneficiaries of the U.S. Government, foreign national civilian/dependents, and civilian, no government connection and (2) U.S. military service members. Chi-square analysis was performed to compare the proportion of dental treatment category procedures on civilian patients compared to those on U.S. military patients. Results During the reporting period, 308 patients were treated for DE in Afghanistan. Civilians treated accounted for 18.5% (n  = 57) of all DEs. Nearly 93.0% of civilians who were treated were U.S. (DoD) civilian employees. Of the 57 civilian patients treated for DE, 61.4% of patients (n  = 35) received oral surgery. There were 251 U.S. military patient encounters (81.5% of all DEs). Restorative dentistry was the most common dental procedure for military personnel DE. When comparing civilian and military patients, civilian patients are statistically more likely than military patients to receive oral surgery treatment for DE (P  < .00001). In Iraq, 3,198 patients were treated for DE during the reporting period. Civilians treated accounted for 18.8% (n  = 601) of all DEs. About 56.9% (n  = 342) of civilians who were treated were U.S. contract employees. Of the 601 civilian patients treated for DE, 37.1% (n  = 223) received oral surgery. There were 2,597 U.S. military patient DE encounters, and restorative dentistry was the most common dental procedure. When comparing civilian and U.S. military patients in Iraq, civilians are statistically less likely to have their DE treated by restorative dentistry (P  < .00001) and are more likely have it treated by oral surgery/extractions (P  < .00001). It is significantly more likely for civilians to have multiple categories of DE that must be treated (P < .00001). Conclusions The primary group of civilians treated for DE in Afghanistan was U.S. civilian employees. The primary group of civilians treated for DE in Iraq were contract employees of the U.S. Government. The primary dental treatment of civilian beneficiaries in both the theaters of operation was oral surgery. This brings into question what dental fitness standards are there for primarily U.S. civilian and contract employees. [ABSTRACT FROM AUTHOR]

Introduction The invasion of Ukraine by Russian troops on February 24, 2022, and the beginning of the full-scale war had huge humanitarian consequences. The major challenges facing the Ukrainian health care system included the disruption of medical infrastructure and logistics, the termination of the supply of expendable materials, significant migration, and a dramatic increase in high-velocity blast and gunshot injuries among combatants and civilians. The aim of the present study was to analyze the challenges and solutions in patient care faced by the Ukrainian system of maxillofacial surgery during the war in different regions of the country. Materials and Methods A cross-sectional study was designed and implemented as an online survey to collect national data concerning maxillofacial surgeons' experiences and professional activities. The study was initiated and supported by Bogomolets National Medical University (Kyiv, Ukraine), the Ukrainian representative of AO CMF (Arbeitsgemeinschaft für Osteosynthesefragen Craniomaxillofacial Surgery) and the University of Helsinki (Finland). The questionnaire was developed by specialists in maxillofacial surgery and sociologists and contained 65 close-ended questions. Surgeons who had not worked in this specialty in inpatient departments of hospitals since at least the beginning of the full-scale war were excluded from the study. We received and analyzed 97 responses that met the abovementioned criteria. The geography of respondents covered all the regions and the main cities of Ukraine, expect for the occupied territories. Results After a year of warfare, the percentage of surgeons who treated patients with blast and gunshot injuries increased from 43.4% to 86.6%. This percentage was higher in military hospitals and in regions located in the vicinity of the front line. We found that, during the war, 78.6% of respondents performed osteosynthesis in cases of high-velocity multifragmented facial bone fractures (in such cases, 58.3% of them strictly followed AO CMF recommendations, while 41.7% performed the fixation based on available hardware, existing technical possibilities and their own preferences). We found that 70.2% of respondents had the opportunity to apply Computer-Aided Design/Computer-Aided Manufacture technology and patient-specific implants for the treatment of gunshot injuries, 38.1% reported that their hospitals were able to perform microsurgical reconstructions for facial defects, 79.4% of respondents reported that their departments received humanitarian aid and support from volunteer organizations (either Ukrainian or international), which significantly facilitated the treatment process. Conclusions According to this nationwide survey of Ukrainian maxillofacial surgeons during a year of the full-scale war, 86.6% of respondents were involved in the treatment of gunshot and ballistic injuries in civilians and combatants. The main problems reported by the respondents were (1) a lack of experience and knowledge related to the treatment of severe wounds, especially by secondary reconstruction, and (2) a deficit of resources (equipment, materials, and medications) under conditions of disrupted logistics and changes in the numbers and nosological distribution of patients. There were the opportunity to transfer the patients to European clinics (29.9%), online consultations (45.4%), collaboration with foreign surgeons who come to Ukraine asvolunteers (32%). [ABSTRACT FROM AUTHOR]

To determine the pharmacokinetics and physiological effects following oral and intravenous (IV) administration of gabapentin in goats. Prospective, crossover study with a 3 week washout period between treatments. A total of eight healthy, client-owned, female goats. Gabapentin (10 mg kg–1) was administered to goats either orally or IV. Gabapentin concentrations were measured in serum samples collected 0–96 hours post-administration using liquid chromatography–quadrupole time-of-flight mass spectrometry. Heart rate, respiratory rate, blood pressure and temperature were recorded before and throughout the study. Correlations of the mean serum concentrations of gabapentin to those of each physiological parameter were determined using the Pearson method. The mean and standard deviation of oral bioavailability for gabapentin was 60.9 ± 11.2%. Maximum serum concentration of gabapentin was lower following oral (1.19 ± 0.29 μg mL–1) than after IV administration (59.76 ± 14.38 μg mL–1, p < 0.0001). Half-lives were longer following PO (8.18 ± 0.57 hours) than after IV administration (1.79 ± 0.06 hours, p < 0.0001). Time to maximum concentration was 6.86 ± 2.27 hours following oral administration. Heart rate was inversely correlated with serum gabapentin concentrations. Slight ataxia was observed in three animals, and one became recumbent following IV gabapentin. Gabapentin is well-absorbed following oral administration to goats but yielded significantly lower serum concentrations than the IV route. The longer half-life of gabapentin following oral than after IV administration may result from prolonged absorption throughout the caprine gastrointestinal tract. IV gabapentin may cause slight ataxia in some goats. [ABSTRACT FROM AUTHOR]

Abstract Adherence and treatment continuation rates of the glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) semaglutide for both oral (O‐SEMA) and subcutaneous injection (SEMA‐SC) remain unknown in real‐world clinical practice. This retrospective observational study compared the 12 month adherence and treatment discontinuation of O‐SEMA and once‐weekly SEMA‐SC in patients with type 2 diabetes using a real‐world claims database. SEMA‐SC initiators were 1:1 propensity score‐matched to O‐SEMA initiators. Non‐adherence was defined as

Background There is scant data regarding the use of oral disease-modifying treatments (oDMT) in patients with relapsing–remitting multiple sclerosis (PwRRMS) from Saudi Arabia. Objective This study aimed to identify the response rate to oDMT in PwRRMS compared to interferon (IFN) in terms of achieving no evidence of disease activity-3 (NEDA-3). Methods This retrospective study was conducted at a tertiary care hospital in Saudi Arabia and included all adult PwRRMS over a 2-year period who were on oDMTs or IFN for

Background This study employed a bidirectional Mendelian Randomization (MR) approach to explore the causal relationships between Oral Lichen Planus (OLP), diabetes mellitus (DM), and glycemic control. It also aims to identify potential pharmacological and herbal treatments that effectively address both OLP and the metabolic dysfunctions associated with DM. Methods This study employs a two-way MR approach to investigate the potential causal relationships between diabetes type and glycated hemoglobin (HbA1c) levels, and the risk of OLP. We analyzed differentially expressed genes from the OLP dataset in the Genomics Expression Omnibus (GEO) database, cross-referencing these with HbA1c-related genes for enrichment analysis. Additionally, the Drug-Gene Interaction Database (DGIdb) and Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to assess the effectiveness of specific drugs, herbs, and ingredients in treating OLP while managing blood glucose levels. Results The MR analysis revealed a significant association between Type 1 Diabetes mellitus (T1DM) and an increased risk of OLP, unlike Type 2 Diabetes mellitus (T2DM). This finding indicates a unique immunological interaction in T1DM that may predispose individuals to OLP. The drug prediction analysis focused on core targets linked to OLP and HbA1c, evaluating the therapeutic potential of retinoic acid, prednisone, and thalidomide for treating OLP and regulating blood glucose levels. Additionally, herbal medicines such as Ecliptae herbaand Amygdalus communis vas, along with herbal ingredients like quercetin, luteolin, and 17-beta-estradiol, were identified for their anti-inflammatory properties and potential to mitigate metabolic dysfunction in diabetes. Conclusion The study highlighted a complex interplay between diabetes and OLP, underscoring the efficacy of integrated therapeutic strategies that target both conditions. The findings suggest that both pharmaceutical and herbal treatments can effectively manage the clinical manifestations of OLP and associated metabolic challenges. This holistic approach to treatment could significantly enhance patient outcomes by addressing the interconnected aspects of these chronic conditions.

BACKGROUND: An unmet need exists to reliably predict the risk of intracranial hemorrhage (ICH) in patients with atrial fibrillation (AF) treated with oral anticoagulants (OACs). HYPOTHESIS: An externally validated model improves ICH risk stratification. METHODS: Independent factors associated with ICH were identified by Cox proportional hazard modeling, using pooled data from the GARFIELD-AF (Global Anticoagulant Registry in the FIELD-Atrial Fibrillation) and ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registries. A predictive model was developed and validated by bootstrap sampling and by independent data from the Danish National Patient Register. RESULTS: In the combined training data set, 284 of 53 878 anticoagulated patients had ICH over a 2-year period (0.31 per 100 person-years; 95% confidence interval [CI]: 0.28-0.35). Independent predictors of ICH included: older age, prior stroke or transient ischemic attack, concomitant antiplatelet (AP) use, and moderate-to-severe chronic kidney disease (CKD). Vitamin K antagonists (VKAs) were associated with a significantly higher risk of ICH compared with non-VKA oral anticoagulants (NOACs) (adjusted hazard ratio: 1.61; 95% CI: 1.25-2.08; p = .0002). The ability of the model to discriminate individuals in the training set with and without ICH was fair (optimism-corrected C-statistic: 0.68; 95% CI: 0.65-0.71) and outperformed three previously published methods. Calibration between predicted and observed ICH probabilities was good in both training and validation data sets. CONCLUSIONS: Age, prior ischemic events, concomitant AP therapy, and CKD were important risk factors for ICH in anticoagulated AF patients. Moreover, ICH was more frequent in patients receiving VKA compared to NOAC. The new validated model is a step toward mitigating this potentially lethal complication.

BACKGROUND: In clinical practice, females with MS often report menstrually-related symptom fluctuations. Hypothetically, use of oral contraceptives (OCs) could reduce these fluctuations, particularly continuous OCs (11+ weeks of consistent exogenous hormones followed by 1 week placebo). OBJECTIVES: To prospectively capture (1) whether neurologic and generalized symptoms vary with menstrual cycle phase and (2) whether type of contraception impacts symptom fluctuations. METHODS: In this two-center pilot study, females with MS and a regular menstrual cycle prospectively tracked their menstrual cycles and completed symptom surveys for up to 6 months. Participants were categorized as 1) users of oral contraceptives, either a) cyclic or b) continuous, or 2) endogenously cycling, either c) hormonal intrauterine device (IUD) users or d) none users (e.g. no hormonal contraception; included condoms, copper IUD, tubal ligation, fertility awareness methods). There was no correction for multiple analyses. RESULTS: Altogether, 47/70 participants (67%) provided >4 weeks of data and were included in the analyses. Mean (SD) age was 35.0 (0.9) years, median (IQR) EDSS was 1.5 (1-2) and mean (SD) SymptoMScreen score was 10.4 (9.6). For endogenously cycling patients (IUD and none users), fatigue (MFIS) was lower in the perimenstrual period than in the luteal period (p

This study presents the results of systematic reviews on adjunctive tools in screening and diagnosis of oral squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD) and to determine if the current literature supports their use as either an adjunctive tool or replacement of gold standard techniques. Systemic reviews and meta-analysis that evaluated adjunctive tools including chemiluminescence, tissue autofluorescence, tissue fluorescence spectroscopy, vital staining and cytology techniques were systematically examined using AMSTAR II. Twenty-seven systematic reviews were included. Five studies had a low quality of evidence, and nine studies had a critically low quality of evidence. This review found limited evidence to recommend chemiluminescence, tissue autofluorescence tools and vital staining as diagnostic tools, but only serve as clinical adjuncts to conventional oral examination. Cytology techniques and narrow-band imaging may be utilised as a non-invasive diagnostic adjunctive tool for the detection of OSCC and the malignant transformation of OPMD. In conclusion, this paper provides evidence on several types of adjunctive tools and provides recommendations on their use in clinical practice. These tools are considered useful as clinical adjuncts but there is insufficient evidence for their use as a diagnostic tool to replace gold standard conventional oral examination and surgical biopsy.

Biofilms are subjected to many environmental pressures that can influence community structure and physiology. In the oral cavity, and many other environments, biofilms are exposed to forces generated by fluid flow; however, our understanding of how oral biofilms respond to these forces remains limited. In this study, we developed a linear rocker model of fluid flow to study the impact of shear forces on Streptococcus gordonii and dental plaque‐derived multispecies biofilms. We observed that as shear forces increased, S. gordonii biofilm biomass decreased. Reduced biomass was largely independent of overall bacterial growth. Transcriptome analysis of S. gordonii biofilms exposed to moderate levels of shear stress uncovered numerous genes with differential expression under shear. We also evaluated an ex vivo plaque biofilm exposed to fluid shear forces. Like S. gordonii, the plaque biofilm displayed decreased biomass as shear forces increased. Examination of plaque community composition revealed decreased diversity and compositional changes in the plaque biofilm exposed to shear. These studies help to elucidate the impact of fluid shear on oral bacteria and may be extended to other bacterial biofilm systems. [ABSTRACT FROM AUTHOR]

Statement of the Problem: One of the main signs of cancer development is increasing of cell proliferation activity. Expression of the Ki-67 as a cell proliferation marker is extensively utilized in pathology studies as an indicator of proliferation in human tumors. According to studies, Ki-67 plays an effective role in the pathology of malignant and pre-malignant oral mucosa lesions. Purpose: The current study aimed to systematically review the Ki-67 expression in oral lichen planus without dysplasia and compare it with oral epithelial dysplasia. Materials and Method: In this meta-analysis, all articles in the English language were searched in databases including Web of Science, PubMed, Embase, Scopus, and Google Scholar until July 2023. MeSH terms and free keywords were used in the search step. Expression of Ki-67 in oral lichen planus and oral epithelial dysplasia was analyzed by Comprehensive Meta-Analysis software. Results: Nine hundred and two articles related to the searched words were found. According to the selection criteria, 12 retrospective articles were selected. Low quality was not observed in any of the records by the Newcastle-Ottawa scale and most of them had a relatively good quality. Totally, 593 patients were examined. The heterogeneity between studies was not significant. The meta-analysis results indicated a significantly lower Ki-67 expression in oral lichen planus without dysplasia in comparison to oral epithelial dysplasia. Conclusion: The more intense expression level of Ki-67 in oral epithelial dysplasia compared with oral lichen planus was observed. The ki-67 expression could be utilized to indicate the existence and intensity of epithelial dysplasia and disease progression. [ABSTRACT FROM AUTHOR]

Background: Functional endoscopic sinus surgery (FESS) is a common procedure for the treatment of chronic sinusitis and minimal bleeding inside the narrow surgical field affects the surgical visualization, prolongs operative time, and increases ocular and intracranial injuries. Our study aims to evaluate and compare the effectiveness of oral versus intravenous Tranexamic acid on surgical field bleeding in endoscopic sinus surgery. Methods: A prospective, randomized, controlled trial enrolled 159 participants (ASA I-II, both sex and age 18–40 years) undergoing FESS who were equally randomized into 3 groups. Group O received 2 gm of TXA orally 2 hours before surgery, Group I received 15 mg/kg of IV TXA slowly after induction of anesthesia, and Group C didn't receive any. Intraoperative surgical field bleeding was assessed by the Wormald grading scale and Surgeon satisfaction on a 5-point Likert scale. At 24 hours post-operatively, the incidence of nasal bleeding, PONV, and D-dimer level were recorded. Results: Showed significantly higher surgical field score, duration of surgery, recovery time, and postoperative (24 hours) D-dimer in group-C (p-value <0.001) with no difference between groups-I and O, while surgeon satisfaction was significantly lower in group-C (p-value <0.001) with no difference between groups-I and O. No differences regarding hemodynamic parameters, postoperative bleeding, pain, and PONV were found. Conclusions: Oral TXA was safe, cheap, and as effective as IV TXA regarding surgical field visualization, surgeon satisfaction, and operative time during FESS; with limited adverse effects and no evidence of thromboembolic complications. [ABSTRACT FROM AUTHOR]

Zulfa Fidi Pranadwista,1 Novia Tri Hasanah,1 Nanan Nur’aeny2 1Oral Medicine Residency Program, Faculty of Dentistry, Padjadjaran University, Bandung, Indonesia; 2Department of Oral Medicine, Faculty of Dentistry, Padjadjaran University, Bandung, IndonesiaCorrespondence: Zulfa Fidi Pranadwista, Email zulfa21004@mail.unpad.ac.idBackground: Oral cavity is the gateway to the digestive system and a window to general human health. Anemia is one of the health problems in the world characterized by various clinical conditions, including in the oral cavity.Purpose: This case report aims to present the results of a clinical investigation of a patient who had oral hematoma and anemia with indigestion symptoms.Case Presentation: A 59-year-old male complained of a lump on his tongue two months prior, which was painless and frequently bleeding. The complaint was followed by abdominal discomfort, difficulty defecating, weight loss, and decreased appetite. The patient only ate porridge and lacked water intake. Intraoral examination showed a blackish-red, irregularly shaped, painless hematoma on the dorsum of the tongue and a negative diascopy test. Hematology examination showed anemia with hemoglobin 6.7g/dL, hematocrit 21.4%, erythrocytes 3.08 x 106/μL, MCV 69.5fL, MCH 21.8pg, and MCHC 31.3g/dL. The diagnosis of the tongue lesion was an oral hematoma.Case Management: Pharmacologic therapy included antifibrinolytic agents and hematinic supplementation. Non-pharmacologic therapy included dental health education, a balanced lifestyle, and avoiding triggers for tongue bleeding. Management in other fields was also carried out in parallel, including oral surgery and internal medicine. The general condition of the patient general condition improved through multidisciplinary monitoring.Conclusion: Clinical investigations that include signs and symptoms of disease in a patient with bleeding disorders such as hematoma and anemia need to be carried out in detailed aid examinations, especially if other symptoms are found, such as digestive disorders.Keywords: anemia, bleeding, hematoma, indigestion, oral