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Phosphodiesterase-4 (PDE4) is involved in the synthesis of inflammatory cytokines that mediate several chronic inflammatory disorders, including psoriasis and atopic dermatitis. In recent years, the therapeutic armamentarium in dermatology has expanded with the introduction of PDE4 inhibitors, both in oral and topical formulations. PDE4 inhibitors have gained increasing interest due to their remarkable safety record and ease of prescription, as evidenced by the recent influx of literature detailing its off-label uses. Apremilast was the first PDE4 inhibitor approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for psoriasis, psoriatic arthritis, and oral ulcers of Behcet's disease. Off-label use has been reported in diverse dermatological conditions, including aphthous stomatitis, chronic actinic dermatitis, atopic dermatitis, cutaneous sarcoidosis, hidradenitis suppurativa, lichen planus, and discoid lupus erythematosus. Roflumilast is a PDE4 inhibitor that was approved by the FDA and the EMA as an oral treatment of chronic obstructive pulmonary disease. Since patent expiration, several generic formulations of oral roflumilast have become available, and various studies have documented its off-label use in psoriasis and other dermatological conditions such as hidradenitis suppurativa, recurrent oral aphthosis, nummular eczema, lichen planus, and Behçet's disease. Topical roflumilast has received FDA approval for treatment of plaque psoriasis and seborrheic dermatitis. The favorable safety profile encourages its long-term use as an alternative to corticosteroids, addressing the chronic nature of many dermatological conditions. New oral PDE4 inhibitors are being developed, such as orismilast (LEO-32731), mufemilast (Hemay005), difamilast (OPA-15406) or lotamilast (E6005/RVT-501), among others. This narrative review provides a comprehensive synthesis of the pharmacology, clinical efficacy, safety profile, and practical considerations regarding the oral and topical use of PDE4 inhibitors in dermatology. [ABSTRACT FROM AUTHOR]

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. Methods: This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation. The database, obtained from the Coconut website, was filtered according to a set of physicochemical descriptors, then was shape screened against the crystal ligand conformation. This filtered database consisting of 26,325 compounds was used for virtual screening against the GLP-1 allosteric site. Results: The results identified ten best hits with the XP score ranging from −9.6 to −7.6 and MM-GBSA scores ranging from −50.8 to −32.4 and another 58 hits from docked pose filter and a second round of XP docking and MM-GBSA calculation followed by molecular dynamics. The analysis of results identified hits from various natural products (NPs) classes, to whom attributed antidiabetic and anti-obesity effects have been previously reported. The results also pointed to β-lactam antibiotics that may be evaluated in drug repurposing studies for off-target effects. The calculated ADMET properties for those hits revealed suitable profiles for further development in terms of bioavailability and toxicity. Conclusions: The current study identified several NPs as potential GLP-1 positive allosteric modulators and revealed common structural scaffolds including peptidomimetics, lactams, coumarins, and sulfonamides with peptidomimetics being the most prominent especially in indole and coumarin cores. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing diarrhea in humans and animals, with increasing antimicrobial resistance posing a growing challenge in recent years. Lytic bacteriophages (phages) offer a targeted and environmentally sustainable approach to combating bacterial infections, particularly in eliminating drug-resistant strains. In this study, ETEC strains were utilized as indicators, and a stable, high-efficiency phage, designated vB_EcoM_JE01 (JE01), was isolated from pig farm manure. The genome of JE01 was a dsDNA molecule, measuring 168.9 kb, and a transmission electron microscope revealed its characteristic T4-like Myoviridae morphology. JE01 effectively lysed multi-drug-resistant ETEC isolates. Stability assays demonstrated that JE01 retained its activity across a temperature range of 20 °C to 50 °C and a pH range of 3–11, showing resilience to ultraviolet radiation and chloroform exposure. Furthermore, JE01 effectively suppressed ETEC adhesion to porcine intestinal epithelial cells (IPEC-J2), mitigating the inflammatory response triggered by ETEC. To investigate the in vivo antibacterial efficacy of phage JE01 preparations, a diarrhea model was established using germ-free mice infected with a drug-resistant ETEC strain. The findings indicated that 12 h post-ETEC inoculation, intragastric administration of phage JE01 significantly reduced mortality, alleviated gastrointestinal lesions, decreased ETEC colonization in the jejunum, and suppressed the expression of the cytokines IL-6 and IL-8. These results demonstrate a therapeutic benefit of JE01 in treating ETEC-induced diarrhea in mice. Additionally, a fluorescent phage incorporating red fluorescent protein (RFP) was engineered, and the pharmacokinetics of phage therapy were preliminarily assessed through intestinal fluorescence imaging in mice. The results showed that the phage localized to ETEC in the jejunum rapidly, within 45 min. Moreover, the pharmacokinetics of the phage were markedly slowed in the presence of its bacterial target in the gut, suggesting sustained bacteriolytic activity in the ETEC-infected intestine. In conclusion, this study establishes a foundation for the development of phage-based therapies against ETEC. [ABSTRACT FROM AUTHOR]

Objective To retrospectively analyze the epidemiological characteristics of supernumerary teeth in patients aged 4-18 years old and the influencing factors on the selection of anesthesia methods, and to provide a reference for the selection of anesthesia plans for children and adolescents with supernumerary teeth. Methods This study is a retrospective study approved by the Institutional Ethics Committee. Based on clinical electronic medical record system and cone beam CT (CBCT) data, a retrospective analysis was conducted on 2 210 patients 4-18 years of age who underwent supernumerary tooth extraction at the School of Stomatology, Fourth Military Medical University from August 2019 to July 2021. Inclusion criteria: ① Age 4-18 years old; and ② The American Society of Anesthesiologists (ASA) classifies anesthesia into grades I-II; and ③ Have complete oral and anesthesia case records and relevant imaging data. Exclusion criteria: ① Incomplete medical records or unclear imaging data; and ② Patients with ASA grade II or above. Patients’ gender and age, the number of supernumerary teeth, arch, location, orientation, eruption status, reason for appointment, anxiety level, degree of cooperation, anesthesia method, and other relevant information were collected and statistically analyzed. Results A total of 1 865 eligible patients were included, with an average age of (8.9±3.2) years old. There were more male patients (71.37%, 1 331 cases) than female patients (28.63%, 534 cases) (P < 0.001), with a gender ratio of 2.49:1. The majority of supernumerary teeth were single (75.97%, 1 417/1 865), primarily located in the maxilla (97.2%, 1 812/1 865) and the anterior dental region (94.2%, 1 757/1 865), and in a centric position (77.3%, 1 442/1 865). The majority of patients with erupted supernumerary teeth were active in seeking treatment (97.67%, 335/343). Patients with supernumerary teeth located in the maxilla and mandible bones, as well as in the nasal floor, were mainly referred to the department for diagnosis, accounting for 94.38%(1 361/1 442) and 90.00% (72/80) (χ2=1 363.24, P < 0.001), respectively. Regarding anesthesia methods, the largest proportion of patients received nitrous oxide sedation-assisted local anesthesia or nerve block anesthesia, accounting for 38.07% (710/1 865), followed by local anesthesia, accounting for 35.23% (657/1 865). The proportion of patients receiving midazolam intravenous sedation with local anesthesia or nerve block anesthesia and general anesthesia was relatively small, accounting for 20.86% (389/1 865) and 5.84% (109/1 865). Patients 13-18 years of age with supernumerary teeth in the mandibular and posterior regions and without anxiety had the highest proportion of local anesthesia use (P < 0.001). In contrast, patients who had supernumerary teeth located at the base of the nose (50%), severe anxiety (94.12%), and poor cooperation (98.18%) had the highest proportion of general anesthesia use (P < 0.001). There was no significant difference (P = 0.35) in the incidence of intraoperative and postoperative complications after the extraction of supernumerary teeth. However, the proportion of anesthesia-related complications, such as dizziness, coughing, and respiratory depression, occurring in patients who received general anesthesia was higher than local anesthesia, accounting for 3.81% (P = 0.006). Conclusion There is a gender difference in the incidence of supernumerary teeth in patients 4-18 years of age, with a higher prevalence in males. The majority of supernumerary teeth are single and located in the maxillary anterior region, predominantly in a centric position. Patients whose teeth had erupted were more likely to seek medical treatment voluntarily, while patients with supernumerary teeth located in the maxilla and mandible bones, as well as in the nasal floor were more likely to be referred to the department. Patients with high levels of anxiety, poor cooperation, young age, multiple teeth, and high surgical difficulty were more inclined to choose general anesthesia.

Objective: Considering inconsistent findings and the absence of published longitudinal studies on large-scale community cohorts, this study aimed to assess the relationship between treatment modalities (injectable vs. oral therapy) and psychiatric symptoms and quality of life (QoL) in individuals with multiple sclerosis. Method: This cross-sectional study involved 42 patients with multiple sclerosis diagnosed according to McDonald’s 2017 criterion. Participants were grouped into those receiving injectable disease-modifying therapies (DMTs) (19 patients), oral DMTs (22 patients), and healthy controls (20 patients). The Expanded disability status scale, Hamilton depression rating scale (HAM-D), 36-item short form survey (SF-36), Hamilton anxiety rating scale (HAM-A), and headache impact test were applied. Results: The healthy control group exhibited statistically higher SF-36 total scores than the oral and injectable therapy groups (p

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Psoriasis is a chronic inflammatory skin disease affecting 2–3% of the global population. Traditional systemic treatments, such as methotrexate, cyclosporine, acitretin and fumaric acid esters, have limited efficacy and are associated with significant adverse effects, necessitating regular monitoring and posing risks of long-term toxicity. Recent advancements have introduced biologic drugs that offer improved efficacy and safety profiles. However, their high cost and the inconvenience of parenteral administration limit their accessibility. Consequently, there is a growing interest in developing new, targeted oral therapies. Small molecules, such as phosphodiesterase 4 inhibitors (e.g. apremilast) and TYK2 inhibitor (e.g. deucravacitinib), have shown promising results with favourable safety profiles. Additionally, other novel oral agents targeting specific pathways, including IL-17, IL-23, TNF, S1PR1 and A3AR, are under investigation. These treatments aim to combine the efficacy of biologics with the convenience and accessibility of oral administration, addressing the limitations of current therapies. This narrative review synthesizes the emerging oral therapeutic agents for psoriasis, focusing on their mechanisms of action, stages of development and clinical trial results.

Background: Since the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources. Methods: A monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options. Results: All patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time. Conclusion: Patients and practitioners prefer oral antitumor therapy—both continuous and 21/7 regimens—over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Enterotoxigenic Escherichia coli (ETEC) is a major pathogen causing diarrhea in humans and animals, with increasing antimicrobial resistance posing a growing challenge in recent years. Lytic bacteriophages (phages) offer a targeted and environmentally sustainable approach to combating bacterial infections, particularly in eliminating drug-resistant strains. In this study, ETEC strains were utilized as indicators, and a stable, high-efficiency phage, designated vB_EcoM_JE01 (JE01), was isolated from pig farm manure. The genome of JE01 was a dsDNA molecule, measuring 168.9 kb, and a transmission electron microscope revealed its characteristic T4-like Myoviridae morphology. JE01 effectively lysed multi-drug-resistant ETEC isolates. Stability assays demonstrated that JE01 retained its activity across a temperature range of 20 °C to 50 °C and a pH range of 3–11, showing resilience to ultraviolet radiation and chloroform exposure. Furthermore, JE01 effectively suppressed ETEC adhesion to porcine intestinal epithelial cells (IPEC-J2), mitigating the inflammatory response triggered by ETEC. To investigate the in vivo antibacterial efficacy of phage JE01 preparations, a diarrhea model was established using germ-free mice infected with a drug-resistant ETEC strain. The findings indicated that 12 h post-ETEC inoculation, intragastric administration of phage JE01 significantly reduced mortality, alleviated gastrointestinal lesions, decreased ETEC colonization in the jejunum, and suppressed the expression of the cytokines IL-6 and IL-8. These results demonstrate a therapeutic benefit of JE01 in treating ETEC-induced diarrhea in mice. Additionally, a fluorescent phage incorporating red fluorescent protein (RFP) was engineered, and the pharmacokinetics of phage therapy were preliminarily assessed through intestinal fluorescence imaging in mice. The results showed that the phage localized to ETEC in the jejunum rapidly, within 45 min. Moreover, the pharmacokinetics of the phage were markedly slowed in the presence of its bacterial target in the gut, suggesting sustained bacteriolytic activity in the ETEC-infected intestine. In conclusion, this study establishes a foundation for the development of phage-based therapies against ETEC.

To evaluate the safety and efficacy of switching from intravenous (IV) to oral antimicrobial therapy in patients with Enterobacterales bacteraemia, after completion of 3–5 days of microbiologically active IV therapy. A multicentre, open-label, randomized trial of adults with monomicrobial Enterobacterales bacteraemia caused by a strain susceptible to ≥1 oral beta-lactam, quinolone, or trimethoprim/sulfamethoxazole. Inclusion criteria included completion of 3–5 days of microbiologically active IV therapy, being afebrile and haemodynamically stable for ≥48 hours, and absence of an uncontrolled source of infection. Pregnancy, endocarditis, and neurological infections were exclusion criteria. Randomization, stratified by urinary source of bacteraemia, was to continue IV (IV Group) or to switch to oral therapy (Oral Group). Agents and duration of therapy were determined by the treating physicians. The primary endpoint was treatment failure, defined as death, need for additional antimicrobial therapy, microbiological relapse, or infection-related re-admission within 90 days. Non-inferiority threshold was set at 10% in the 95% CI for the difference in the proportion with treatment failure between the Oral and IV Groups in the modified intention-to-treat population. The protocol was registered at ClinicalTrials.gov (NCT04146922). In the modified intention-to-treat population, treatment failure occurred in 21 of 82 (25.6%) in the IV Group, and 18 of 83 (21.7%) in the Oral Group (risk difference –3.7%, 95% CI –16.6% to 9.2%). The proportions of subjects with any adverse events (AE), serious AE, or AE leading to treatment discontinuation were comparable. In patients with Enterobacterales bacteraemia, oral switch, after initial IV antimicrobial therapy, clinical stability, and source control, is non-inferior to continuing IV therapy. [ABSTRACT FROM AUTHOR]

Injectable antiretroviral treatment (ART) represents a new effective and potentially more convenient alternative to oral ART for people living with HIV (PLWH). This study assessed preferences of PLWH for long-acting injectable compared with oral ART in the Netherlands. A labelled discrete choice experiment presented 12 choice sets of long-acting injectable and oral ART. PLWH were asked to select their preferred ART, described by six attributes: location of administration, dosing frequency, risk of short-term side effects, drug–drug interaction, forgivability, and food and mealtime restrictions. Random parameters logit and latent class models were used to estimate preferences of PLWH. 98.6% of 76 respondents were experienced oral ART users that had taken ART for a median of 12 years (Q1–Q3: 7.0–20.0). 30 (39.5%) respondents chose long-acting injectable ART in all choice tasks and 22 (28.9%) always chose oral ART. The random parameter model showed that, on average, respondents significantly favoured long-acting injectable ART over oral ART, preferred administration of the long-acting injectable ART at home, and a less frequent regimen. The latent class model confirmed one class strongly preferring long-acting injectable ART and one class slightly preferring oral ART. This study highlights the value for both long-acting injectable and oral ART. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation is closely related to Alzheimer's Disease (AD) pathology, hence supplements with anti-inflammatory property could help attenuate the progression of AD. This study was conducted to evaluate the potential anti-inflammatory effects of liposome encapsulated thymol (LET), administered orally, in prevention of Alzheimer in a rat model by anti-inflammatory mechanisms. Methods: The rats were grouped into six groups (n = 10 animals per group), including Control healthy (Con), Alzheimer's disease (AD) model, AD model treated with free thymol in 40 and 80 mg/kg body weight (TH40 and TH80), AD model treated with LET in 40 and 80 mg/kg of body weight (LET40 and LET80). The behavioral response of step through latency (Passive Avoidance Test), concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) and brain-derived neurotrophic factor (BDNF) were assessed in serum and hippocampus. Results: The results showed that significant increase in concentrations of IL-1β (P = 0.001), IL-6 (P = 0.001), TNF-α (P = 0.001) and COX-2 (P = 0.001) in AD group compared with healthy control rats. AD induction significantly reduced step through latency and revealed deficits in passive avoidance performance. The results also showed the treatment with free thymol especially in higher concentrations and also LTE could decrease serum concentrations of IL-1β (P

BackgroundSince the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources.MethodsA monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options.ResultsAll patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time.ConclusionPatients and practitioners prefer oral antitumor therapy—both continuous and 21/7 regimens—over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer.

BACKGROUND: Streptococcus anginosus group is a common cause of pediatric intracranial infections but treatment recommendations, including use of oral therapy, are poorly defined. METHODS: We performed a retrospective review from 2004 to 2019 of all patients with S anginosus group pyogenic intracranial infections at Childrens Hospital Colorado, highlighting patients transitioned to oral therapy. The primary endpoint was worsening infection necessitating intravenous antibiotics or a source control procedure after transition to oral therapy. RESULTS: Of 107 patients with S anginosus intracranial infections, 61 were transitioned to exclusive oral therapy after a median intravenous duration of 37 days, overwhelmingly with a levofloxacin-based regimen. Only 1 treatment failure was noted in a patient who did not fill their prescription. Patients with epidural infections were more likely to be transitioned to oral therapy within the first 28 days of treatment (defined as early). Patients with parenchymal infections, bacteremia, co-pathogens, higher inflammatory markers, and requiring >1 source control procedure were less likely to be transitioned early to oral therapy. Complications of a central catheter and/or intravenous medications contributed to 56% of oral transitions. CONCLUSIONS: Levofloxacin-based oral regimens were effective and well tolerated. Patients with less severe infections were more likely to be transitioned early to oral therapy. Criteria for transitioning patients to oral antibiotics for intracranial infections should be established to minimize risks inherent with central catheters.

Aim: To compare the effectiveness of in-class transition to all-oral ixazomib-lenalidomide-dexamethasone (IRd) following parenteral bortezomib (V)-based induction versus continued V-based therapy in US oncology clinics. Patients & methods: Non-transplant eligible patients with newly diagnosed multiple myeloma (MM) receiving in-class transition to IRd (N = 100; US MM-6), or V-based therapy (N = 111; INSIGHT MM). Results: Following inverse probability of treatment weighting, overall response rate was 73.2% with IRd versus 57.5% with V-based therapy (p < 0.0001). Median duration of treatment was 10.8 versus 5.3 months (p < 0.0001). Overall, 18/24% of patients discontinued IRd/V-based therapy due to adverse events. Conclusion: IRd after V-based induction was associated with significantly improved overall response rate and duration of treatment than continued V-based combination therapy. Clinical Trial Registration: US MM-6: NCT03173092; INSIGHT MM: NCT02761187 (ClinicalTrials.gov) [ABSTRACT FROM AUTHOR]

The overall low-quality evidence concerning the clinical benefits of different antibiotic regimens for the treatment of infective endocarditis (IE), which has made it difficult to strongly support or reject any regimen of antibiotic therapy, has led to a discrepancy between the available guidelines and clinical practice. In this complex scenario, very recently published guidelines have attempted to fill this gap. Indeed, in recent years several antimicrobials have entered the market, including ceftobiprole, ceftaroline, and the long-acting lipoglycopeptides dalbavancin and oritavancin. Despite being approved for different indications, real-world data on their use for the treatment of IE, alone or in combination, has accumulated over time. Furthermore, an old antibiotic, fosfomycin, has gained renewed interest for the treatment of complicated infections such as IE. In this narrative review, we focused on new antimicrobials and therapeutic strategies that we believe may provide important contributions to the advancement of Gram-positive IE treatment, providing a summary of the current in vitro, in vivo, and clinical evidence supporting their use in clinical practice. [ABSTRACT FROM AUTHOR]

Abstract Background Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. Methods This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. Results Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5–80.5] years; Charlson Comorbidity Index 2 [0–4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500–2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32–61; 21–86), 29 (19–82; 8–251), and 86 (59–125; 37–337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5–350) days. Conclusions In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided.

Background. Peyronie’s disease is a disease characterized by chronic inflammation of the protein membrane of the fibrous tissue of the penis. Oral pharmacotherapy allows a long-term effect on the mechanisms of formation of fibrous plaque.Aim. To evaluate the degree of change in complaints against the background of the complex drug Peyroflex® and its effectiveness.Materials and methods. The study was conducted as a prospective observational study. The study included 43 patients with complaints of pain in the penis area during erection or at rest, curvature of the penis, the presence of palpable plaque in the area of the cavernous bodies. Men took Peyroflex® on a regular basis, one capsule (410 mg) 2 times a day for 6 months or until the pain disappeared during erection, but not less than 6 months.Results. The intensity of pain after 3 and 6 months of taking Peyroflex® decreased by 47.8 and 78.3 %, respectively. The severity of penile curvature showed a tendency to decrease by 7.5 % after 3 doses of Peyroflex® and remained stable after 6 months. The plaque area according to the results of ultrasound examination after 3 and 6 months of taking Peyroflex® decreased by 14.7 and 17.2 %, respectively.Conclusion. Peyroflex® can be recommended for use in the active phase of Peyronie’s disease both in monotherapy and in combination with other methods of treatment (extracorporeal shock wave therapy, physiotherapy, etc.).

Background: Methicillin-susceptible Staphylococcus aureus (MSSA) is the most common causative microorganism of pyogenic vertebral osteomyelitis (PVO). Although oral antimicrobial therapy with first-generation cephalosporins can treat MSSA infection, data on PVO are scarce. This study evaluated the treatment efficacy of cephalexin as oral antibiotic therapy for MSSA-induced PVO. Methods: This retrospective study included adult patients treated with oral cephalexin as the completing treatment for PVO with MSSA bacteremia from 2012 to 2020. Treatment effectiveness of cephalexin was evaluated by comparing improvement (5-point scale; score ≥ 4/5 indicates treatment success) in symptoms and laboratory and imaging results between intravenous antimicrobial and oral cephalexin treatment. Results: Among 15 participants (8 [53%] women; median [interquartile range, IQR], age 75 [67.5–80.5] years; Charlson Comorbidity Index 2 [0–4]), 10 (67%) had lumbar spine lesions, 12 (80%) had spinal abscesses, and 4 (27%) had remote abscesses; no patients had concomitant endocarditis. In 11 patients with normal renal function, cephalexin 1,500–2,000 mg/day was administered. Five patients (33%) underwent surgery. Median (IQR; range) duration (days) of intravenous antibiotics, cephalexin, and total treatment was 36 (32–61; 21–86), 29 (19–82; 8–251), and 86 (59–125; 37–337), respectively. Cephalexin had an 87% treatment success rate without recurrence during a median follow-up of 119 (IQR, 48.5–350) days. Conclusions: In patients with MSSA bacteremia and PVO, antibiotic treatment completion with cephalexin is a reasonable option, even in cases with spinal abscess, if at least 3 weeks of effective intravenous antimicrobial therapy is provided. [ABSTRACT FROM AUTHOR]

Simple Summary: Recipients of a haematopoietic stem cell transplantation must follow a complex treatment regimen that could reduce medication adherence (MA). Updated prevalence rates of MA, as well as factors promoting or hindering it and its outcomes, have not been summarised. Therefore, the primary aim of this review was to summarise the available oral MA prevalence data among adults who have received an allogeneic transplant and the tools used to measure it. The secondary aims were to find predictors and risk factors of medication non-adherence (MNA), the effectiveness of interventions, and the clinical outcomes of MNA. The MA is still an issue among these patients who report suboptimal prevalence rates. More than one measurement method should be considered when planning studies regarding MA. Additional research is needed to investigate other risk factors of MNA and to develop multidisciplinary interventions to improve MA, including the role of the caregivers' and patients' perceptions and MNA outcomes. This endeavour would produce more robust evidence to inform clinical practice. Recipients of a haematopoietic stem cell transplantation (HSCT) may experience issues in medication adherence (MA) when discharged. The primary aim of this review was to describe the oral MA prevalence and the tools used to evaluate it among these patients; the secondary aims were to summarise factors affecting medication non-adherence (MNA), interventions promoting MA, and outcomes of MNA. A systematic review (PROSPERO no. CRD42022315298) was performed by searching the Cumulative Index of Nursing and Allied Health (CINAHL), Cochrane Library, Excerpta Medica dataBASE (EMBASE), PsycINFO, PubMed and Scopus databases, and grey literature up to May 2022 by including (a) adult recipients of allogeneic HSCT, taking oral medications up to 4 years after HSCT; (b) primary studies published in any year and written in any language; (c) with an experimental, quasi-experimental, observational, correlational, and cross-sectional design; and (d) with a low risk of bias. We provide a qualitative narrative synthesis of the extracted data. We included 14 studies with 1049 patients. The median prevalence of MA was 61.8% and it has not decreased over time (immunosuppressors 61.5% [range 31.3–88.8%] and non-immunosuppressors 65.2% [range 48–100%]). Subjective measures of MA have been used most frequently (78.6%) to date. Factors affecting MNA are younger age, higher psychosocial risk, distress, daily immunosuppressors, decreased concomitant therapies, and experiencing more side effects. Four studies reported findings about interventions, all led by pharmacists, with positive effects on MA. Two studies showed an association between MNA and chronic graft-versus-host disease. The variability in adherence rates suggests that the issues are relevant and should be carefully considered in daily practice. MNA has a multifactorial nature and thus requires multidisciplinary care models. [ABSTRACT FROM AUTHOR]

Background: Orally administrated agents play a key role in the management of prostate cancer, providing a convenient and cost-effective treatment option for patients. However, they are also associated with adherence issues which can compromise therapeutic outcomes. This scoping review identifies and summarizes data on adherence to oral hormonal therapy in advanced prostate cancer and discusses associated factors and strategies for improving adherence. Methods: PubMed (inception to 27 January 2022) and conference databases (2020–2021) were searched to identify English language reports of real-world and clinical trial data on adherence to oral hormonal therapy in prostate cancer using the key search terms 'prostate cancer' AND 'adherence' AND 'oral therapy' OR respective aliases. Results: Most adherence outcome data were based on the use of androgen receptor pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Self-reported and observer-reported adherence data were used. The most common observer-reported measure, medication possession ratio, showed that the vast majority of patients were in possession of their medication, although proportion of days covered and persistence rates were considerably lower, raising the question whether patients were consistently receiving their treatment. Study follow-up for adherence was generally around 6 months up to 1 year. Studies also indicate that persistence may drop further with longer follow-up, especially in the non-mCRPC setting, which may be a concern when years of therapy are required. Conclusions: Oral hormonal therapy plays an important role in the treatment of advanced prostate cancer. Data on adherence to oral hormonal therapies in prostate cancer were generally of low quality, with high heterogeneity and inconsistent reporting across studies. Short study follow-up for adherence and focus on medication possession rates may further limit relevance of available data, especially in settings that require long-term treatment. Additional research is required to comprehensively assess adherence. [ABSTRACT FROM AUTHOR]

Introduction: Oral sensory problems in Autism Spectrum Disorder (ASD) are mainly due to lack of sensory-motor synchronisation and incomplete neuromuscular development. Direct oral stimulation can play a significant role as a part of oral therapy, because the speech outcome by Speech Therapy (ST) has subjective variation and requires a long period of time. The other oral muscular therapy has lack of specificity and sensitivity. However, the direct oral stimulation in the form of appliance therapy has not yet been investigated. Aim: To explore the precise role of Speech-sensory Appliance (SSA) on speech disorder and associated oral sensory problems in ASD children. Materials and Methods: In this single-arm, Randomised Controlled Trial (RCT), 40 ASD-diagnosed children between the ages of 4 and 11 will be involved. The study participants will be split into two groups of 20 each at random. While the other group will be exposed to SSA+ST therapy, one of the groups will undergo SSA therapy. The speech therapist was unaware of the group of children who received both therapies (blind). Analyses of the results will be conducted utilising voice recordings and Visual Analogue Scales (VAS). Before and after therapy, the voice recording graph will be collected. Parents will be given a short questionnaire as part of the VAS to track any changes in feeding behaviour. Expected Results: SSA therapy that is 3D printed will result in better speaking outcomes and feeding behaviour. Conclusion: If the current study's hypothesis is confirmed, direct oral stimulation can be employed either alone or in conjunction with ST to improve participants with ASD's speech outcomes and feeding behaviour. [ABSTRACT FROM AUTHOR]

Abstract Treatment goals in bladder pain syndrome (BPS) or interstitial cystitis (IC) focusing on relieving symptoms to improve quality of life and avoiding adverse events (AEs) since curative treatment for BPS/IC is not available. The readily available pharmacologic options for BPS/IC including oral, intravesical, and transdermal therapy. The purpose of this study is to review randomized trial studies over the last 15 years examining the efficacy and safety of oral pharmacological and supplementary therapies for BPS/IC. A systematic search was conducted in PubMed and Medline Library. Only randomized-controlled trials and randomized comparative trials published between 2005 and 2020 on the efficacy and safety of oral therapies for BPS/IC were included. The keywords used were “bladder pain syndrome”, or “interstitial cystitis”, and “random” or “trial”. From 629 articles, nine were included in this review. Oral therapies included consist of cyclosporine A (CyA), amitriptyline, amitriptyline plus alpha lipoic acid (ALA) and omega-3 fatty acids (n-3 PUFA), PD-0299685, sildenafil, pentosan polysulfate sodium (PPS), AQX-1125, and hydrogen-rich water. Among retrieved trials, amitriptyline in combination with ALA and n-3 PUFA, sildenafil, and cyclosporine A proved their efficacy for BPS/IC. Sildenafil was generally well tolerated, while amitriptyline and CyA must be used with caution, the supplementation of ALA/n-3 PUFAs possibly lower dosage of amitriptyline, subsequently reduce its AEs. CyA was superior to PPS but possessed greater AEs. Further studies focusing on etiopathology and phenotype differentiation of this syndrome will greatly contribute to the development of effective therapy.

MicroRNAs (miRNAs), that is, short non-coding RNA molecules, have been found in different common foods, like fruits and vegetables, meat and its products, milk (including human breast milk) and dairy products, as well as honey and herbs. Moreover, they are isolated from supernatants from cultures of various mammalian cells. A growing amount of evidence appears to support the idea of using miRNAs as therapeutics. One possible and promising route of administration is oral, which is considered noninvasive and well-tolerated by patients. Association with extracellular vesicles (EVs), nanoparticles, RNA-binding proteins, lipoproteins, or lipid derivatives, protects miRNAs from an unfavorable gastrointestinal environment (including salivary and pancreatic RNases, low pH in the stomach, digestive enzymes, peristaltic activity and microbial enzymes). Such protection likely favors miRNA absorption from the digestive tract. Internalization of miRNA by gastric and intestinal cells as well as effects on the gut microbiota by orally delivered miRNA have recently been described. Furthermore, gene regulation by orally administered miRNAs and their immunomodulatory properties indicate the possibility of cross-species or cross-kingdom communication through miRNA. In addition to the local effects, these molecules may enter the circulatory system and reach distant tissues, and thus cell-free nucleic acids are promising candidates for future selective treatments of various diseases. Nonetheless, different limitations of such a therapy imply a number of questions for detailed investigation. [ABSTRACT FROM AUTHOR]

Objective: New Delhi metallo-β-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) is a globally growing threat. We sought to describe the microbiology, management and outcomes of patients with this infection at our facility., Methods: This is a descriptive case series of patients with NDM-producing Escherichia coli isolated from culture in Detroit between July 2021 and February 2023. Demographics, risk factors, clinical characteristics, management and outcomes were described., Results: Nine patients were included in the study. Most patients were female with a median age of 67 years. Hepatobiliary disease accounted for 90% of underlying conditions. Nearly all patients had prior antibiotic exposure and the most common specimen source was intra-abdominal fluid. Three patients were not treated due to colonisation; among those treated, the majority received trimethoprim-sulfamethoxazole. The median treatment duration and length of stay were 7 and 15.5 days, respectively. Six (67%) patients survived., Conclusions: This report describes a large case series of NDM-producing E. coli infection. Patients with significant comorbidities remain at high risk for CRE infection. Antibiotic options for the treatment of NDM organisms are very limited; new and effective therapies are urgently needed., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

PICO question In cats with chronic bronchospasm and airway hypersensitivity (asthma) do oral glucocorticoids or inhaled glucocorticoids more effectively control the clinical signs? Clinical bottom line Category of research question Treatment The number and type of study designs reviewed Three prospective randomised clinical trials were appraised. Two of the studies followed a crossover design and had a control group, whilst the third study described an interrupted time series Strength of evidence Weak Outcomes reported The available studies deemed a reduction in eosinophilia on bronchoalveolar lavage fluid analysis, and a reduction in airway resistance as markers of treatment efficacy Conclusion There is weak evidence to suggest equal treatment efficacy of oral and inhaled glucocorticoid therapy for management of feline asthma. Higher powered studies would be required before a definitive recommendation can be made How to apply this evidence in practice The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources. Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.

Introduction: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. Methods: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. Results: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59–75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8–14.0) and 5.3 months (95% CI: 2.8–9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child–Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). Conclusions: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS. [ABSTRACT FROM AUTHOR]

Background Interest in shorter antimicrobial regimens and oral treatment for osteoarticular infections is growing. The aim of this study is to assess whether there is an association between the administration of an entirely oral antibiotic therapy (OT) and the clinical outcome of native vertebral osteomyelitis (NVOs). Methods We conducted a single-center, retrospective, observational study on consecutive patients with pyogenic NVOs over a 10-year period (2008–2018). We performed multivariate logistic regression analysis to identify risk factors for clinical failure, both in the whole population and in subgroups. The impact of OT versus standard treatment (intravenous induction followed by oral treatment whenever possible) was assessed in patients with a non-multidrug-resistant microorganism (MDRO) etiology, and the impact of a rifampin-containing regimen was assessed in patients affected by NVOs caused by staphylococci or of unknown etiology. Results The study population included 249 patients, and 33 (13.3%) experienced clinical failure; the OT group consisted of 54 patients (21.7%). Multivariate regression analysis of the whole population selected Charlson comorbidity index (adjusted odds ratio [aOR], 1.291; 95% confidence interval [CI], 1.114–1.497; P  = .001) and MDRO etiology (aOR, 3.301; 95% CI, 1.368–7.964; P  = .008) as independent factors for clinical failure. Among patients affected by a non-MDRO NVO, OT was not associated with an increased risk of clinical failure (aOR, 0.487; 95% CI,.133–1.782; P  = .271), even after adjustment for the propensity score of receiving OT. In the subgroup of patients with staphylococcal or unknown etiology, NVO rifampin was independently associated with favorable outcome (aOR, 0.315; 95% CI,.105–.949; P  = .040). Conclusions An entirely oral, highly bioavailable treatment, including rifampin, may be as effective as parenteral treatment in selected patients with NVOs. [ABSTRACT FROM AUTHOR]

Itch (or pruritus) is an unpleasant sensation, inducing the desire to scratch. It is also a major and distressing symptom of many skin and systemic diseases. The involvement of histamine, which is a major itch mediator, has been extensively examined. Recent studies suggest that histamine-independent pathways may play roles in chronic itch. Therefore, antihistamines are not always effective in the treatment of patients with chronic itch. The development of biologics and κ-opioid receptor (KOR) agonists has contributed to advances in the treatment of itch; however, since biologics are expensive for patients to purchase, some patients may limit or discontinue their use of these agents. Furthermore, KOR agonists need to be prescribed with caution due to risks of side effects in the central nervous system. Janus kinase (JAK) inhibitors are sometimes associated with side effects, such as infection. In this review, we summarize antidepressants, antineuralgics, cyclosporine A, antibiotics, crotamiton, phosphodiesterase 4 inhibitor, botulinum toxin type A, herbal medicines, phototherapy, and acupuncture therapy as itch treatment options other than antihistamines, biologics, opioids, and JAK inhibitors; we also explain their underlying mechanisms of action. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the disease and improve the quality of life. Optimal and early treatment could enable the prevention of their complications. Small molecules, administrated as oral agents, have the capacity of overcoming the limitations of biologic agents (i.e., parenteral administration, rapidity of action and primary and secondary non-responsiveness). Of special interest are results from the use of oral sphingosine 1-phosphate (S1P) receptor modulators (ozanimod, etrasimod, fingolimod and laquinimod), based on S1P activities to target lymphocyte recirculation in the mucosa, acting as immunosuppressive agents. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks. Cost-effectiveness studies and head-to-head trials are needed to better define their place in therapy. This review summarizes these emerging data published by PubMed and EMBASE databases and from ongoing clinical trials on the safety and efficacy of selectivity of S1P modulators in the treatment of IBD. [ABSTRACT FROM AUTHOR]

• Key finding: The biggest impact of lung cancer was on financial and professional life. • More patients with stage I–III reported fear and anxiety than those with stage IV. • Patients were open to novel treatments, but lacked information on biomarkers. • Sixty percent of patients preferred oral vs. injectable/intravenous administration. • The patient perspective needs to be taken into account in treatment decision making. To understand European non-small cell lung cancer (NSCLC) patients' perceptions of disease burden, treatment, and future expectations of treatment and care. A 32-item online survey was conducted on a sample of NSCLC patients across Europe. Descriptive statistics were used to analyse the data. Results were presented by disease stage (I–III vs. IV). NSCLC patients (N = 292) from 10 countries responded. Most patients resided in France, Spain, Italy, Germany and UK, with 16 patients from five other countries. Patients' knowledge of biomarker testing was limited (23% of 376 responses indicated no knowledge). Patients reported fear (stage I–III: 40%, stage IV: 27%), anxiety (stage I–III: 44%, stage IV: 33%) and depression (stage I–III: 24%, stage IV: 20%), but also hope (stage I–III: 57%, stage IV: 59%). Professional status was majorly impacted for 43% of stage I–III patients and 58% stage IV patients. Household finances were impacted for ∼70% of all patients. Oral treatment was preferred (60%), and respondents understood dosing schedules (stage I–III: 82%, stage IV: 97%) remembering to take medications (stage I–III: 82%, stage IV: 87%). Most respondents were willing to take more pills, but some indicated that this would be difficult. Approximately half of the patients in this survey were aware of clinical trial options, but most lacked information about their molecular tumor profile, making it difficult for patients to engage in discussions about their care. The results also suggest that NSCLC patients have significant information and support needs, especially in the areas of emotional and financial burden. Action is needed to address these burdens associated with NSCLC. Furthermore, patients should be provided with the information needed to actively participate in treatment decisions. [ABSTRACT FROM AUTHOR]

Treatment goals in bladder pain syndrome (BPS) or interstitial cystitis (IC) focusing on relieving symptoms to improve quality of life and avoiding adverse events (AEs) since curative treatment for BPS/IC is not available. The readily available pharmacologic options for BPS/IC including oral, intravesical, and transdermal therapy. The purpose of this study is to review randomized trial studies over the last 15 years examining the efficacy and safety of oral pharmacological and supplementary therapies for BPS/IC. A systematic search was conducted in PubMed and Medline Library. Only randomized-controlled trials and randomized comparative trials published between 2005 and 2020 on the efficacy and safety of oral therapies for BPS/IC were included. The keywords used were "bladder pain syndrome", or "interstitial cystitis", and "random" or "trial". From 629 articles, nine were included in this review. Oral therapies included consist of cyclosporine A (CyA), amitriptyline, amitriptyline plus alpha lipoic acid (ALA) and omega-3 fatty acids (n-3 PUFA), PD-0299685, sildenafil, pentosan polysulfate sodium (PPS), AQX-1125, and hydrogen-rich water. Among retrieved trials, amitriptyline in combination with ALA and n-3 PUFA, sildenafil, and cyclosporine A proved their efficacy for BPS/IC. Sildenafil was generally well tolerated, while amitriptyline and CyA must be used with caution, the supplementation of ALA/n-3 PUFAs possibly lower dosage of amitriptyline, subsequently reduce its AEs. CyA was superior to PPS but possessed greater AEs. Further studies focusing on etiopathology and phenotype differentiation of this syndrome will greatly contribute to the development of effective therapy. [ABSTRACT FROM AUTHOR]

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Introduction: Patient adherence is a major challenge for the successful management of any chronic disease, and ulcerative colitis (UC) is no exception. Patient adherence is closely related to patient preference of medication and formulation used. Aim: The aim of this study was to investigate patient and physician perspectives around UC treatment preference. Methods: This study was conducted in France, Germany, Spain, and the UK. Physicians and UK inflammatory bowel disease (IBD) nurses answered an online questionnaire. In addition, adult mild-to-moderate UC patients, treated with oral mesalazine, were invited to answer a 30-min online survey which included a conjoint exercise. Results: 400 patients, 160 physicians, and 20 IBD nurses participated in the survey. 68% of patients were taking tablets and 32% granules. Physicians stated that from their perspective patients are more adherent to tablets than granules (76% vs. 24%), patients tended to have better relief of symptoms with tablets (69% vs. 31%), and patients found tablets to be the most convenient formulation (61% vs. 39%). From the patients’ perspective, when questioned which formulation they prefer, 58% answered tablets, 37% granules, and 5% none of these. When patients were asked about some negative attributes of tablets, the highest agreement was for “I would like to take fewer each day” (6.1/10) and “I wish I could take fewer at a time” (5.4/10). Conclusions: The majority of UC patients in this survey prefer the tablet formulation. A high strength tablet overcoming the high pill burden could be a good solution to address patient expectations.

Introduction: The development of oral therapies impacts the management of acute myeloid leukemia and myelodysplastic syndromes, especially for targetable mutations including IDH1/2 ., Areas Covered: We discuss IDH1/2 activity and inhibitor therapy in various settings, including monotherapy, combination therapy with hypomethylating agents, and other approaches., Expert Opinion: Olutasidenib, enasidenib, and ivosidenib are approved for relapsed AML. Ivosidenib is approved for relapsed MDS and alone or with azacitidine in newly diagnosed AML. However, unanswered questions exist. In newly diagnosed AML, ivosidenib + azacitidine shows a survival benefit compared to azacitidine, but it is unknown whether ivosidenib + azacitidine demonstrates improved survival compared to ivosidenib. Ivosidenib + azacitidine demonstrated a survival benefit not seen with enasidenib + azacitidine. It is unclear whether newly diagnosed AML should be treated with azacitidine + ivosidenib or azacitidine + venetoclax. Azacitidine + venetoclax shows excellent response rates in IDH mutated disease. Retrospective data show low response rates of IDH inhibitor therapy post-venetoclax whereas HMA + venetoclax retains activity post IDH inhibition. The role of IDH inhibition post-transplant is unclear. Single-arm studies show post-transplant maintenance is safe; however, randomized trials are needed. Similarly, IDH inhibitors can be combined with chemotherapy however randomized studies are needed.

Objectives: The present study aimed to investigate the susceptibility profiles of vancomycin-resistant Enterococcus isolates in urine culture to create an antibiogram to guide selection of oral antimicrobials in British Columbia (BC), Canada., Methods: An audit was conducted on all urine cultures reported from January 1, 2021, to December 31, 2023, in LifeLabs BC microbiology laboratories. Enterococcus species in urine were routinely tested with ampicillin, ciprofloxacin, nitrofurantoin, tetracycline, and vancomycin. Linezolid and fosfomycin were tested in selected cases., Results: Three hundred and thirty-five vancomycin-resistant Enterococcus faecium , 47 vancomycin-resistant Enterococcus faecalis , 48 Enterococcus gallinarum , 25 Enterococcus casseliflavus , and no Enterococcus flavescens isolates were reported in urine culture. Vancomycin-resistant E. faecium isolates were >90% susceptible to linezolid, but <15% susceptible to ampicillin, ciprofloxacin, nitrofurantoin, and tetracycline. Vancomycin-resistant E. faecalis isolates were >90% susceptible to ampicillin, linezolid, and nitrofurantoin, but <10% susceptible to ciprofloxacin and tetracycline. E. casseliflavus isolates were >90% susceptible to ampicillin, nitrofurantoin, and tetracycline. E. gallinarum isolates were >90% susceptible to ampicillin and nitrofurantoin. In the seven and 263 selected cases of vancomycin-resistant E. faecium and E. faecalis , respectively, fosfomycin susceptibility rates were 57% and 86%, respectively., Conclusions: Ampicillin and nitrofurantoin may be considered for urinary tract infections secondary to vancomycin-resistant E. faecalis , E. casseliflavus , and E. gallinarum . Tetracycline may also be considered for E. casseliflavus . Linezolid remained to be the only reliable oral antimicrobial for vancomycin-resistant E. faecium ., Competing Interests: Eugene Y.H. Yeung is working as a microbiologist, physician, pharmacist, and clinical assistant professor. The views and opinions expressed are those of the authors and do not necessarily reflect the views or positions of their employers., (© 2024 Bladder, All rights reserved.)

Background Streptococcus anginosus group is a common cause of pediatric intracranial infections but treatment recommendations, including use of oral therapy, are poorly defined. Methods We performed a retrospective review from 2004 to 2019 of all patients with S anginosus group pyogenic intracranial infections at Children's Hospital Colorado, highlighting patients transitioned to oral therapy. The primary endpoint was worsening infection necessitating intravenous antibiotics or a source control procedure after transition to oral therapy. Results Of 107 patients with S anginosus intracranial infections, 61 were transitioned to exclusive oral therapy after a median intravenous duration of 37 days, overwhelmingly with a levofloxacin-based regimen. Only 1 treatment failure was noted in a patient who did not fill their prescription. Patients with epidural infections were more likely to be transitioned to oral therapy within the first 28 days of treatment (defined as "early"). Patients with parenchymal infections, bacteremia, co-pathogens, higher inflammatory markers, and requiring >1 source control procedure were less likely to be transitioned early to oral therapy. Complications of a central catheter and/or intravenous medications contributed to 56% of oral transitions. Conclusions Levofloxacin-based oral regimens were effective and well tolerated. Patients with less severe infections were more likely to be transitioned early to oral therapy. Criteria for transitioning patients to oral antibiotics for intracranial infections should be established to minimize risks inherent with central catheters. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a type of inflammatory bowel disease (IBD) characterized by chronic gastrointestinal inflammation. In most patients, the disease cycles through periods of remission and exacerbations. The complex etiology involves multiple factors including environmental, genetic, and immune causal elements. Janus Kinase (JAK) family is an essential component of a cytokine-signaling cascade partially responsible for the pathogenesis of UC. Treating UC presents difficulties despite various therapeutic options. Medications that block the JAK-signaling pathway can interfere with the inflammatory pathway of UC and possibly reduce symptoms and frequency of exacerbations. Tofacitinib is an oral pan-JAK inhibitor, primarily of JAK1 and JAK3, that was recently approved by the Food and Drug Administration (FDA) for the chronic treatment of UC in 2018. The following review describes the newly approved Janus kinase inhibitor, tofacitinib, including its pharmacokinetic properties, efficacy and safety data, and potential place in therapy. [ABSTRACT FROM AUTHOR]

Background: People with cystic fibrosis are susceptible to pulmonary infection with Pseudomonas aeruginosa. This may become chronic and lead to increased mortality and morbidity. If treatment is commenced promptly, infection may be eradicated through prolonged antibiotic treatment. Objective: To compare the clinical effectiveness, cost-effectiveness and safety of two eradication regimens. Design: This was a Phase IV, multicentre, parallel-group, randomised controlled trial. Setting: Seventy UK and two Italian cystic fibrosis centres. Participants: Participants were individuals with cystic fibrosis aged > 28 days old who had never had a P. aeruginosa infection or who had been infection free for 1 year. Interventions: Fourteen days of intravenous ceftazidime and tobramycin or 3 months of oral ciprofloxacin. Inhaled colistimethate sodium was included in both regimens over 3 months. Consenting patients were randomly allocated to either treatment arm in a 1 : 1 ratio using simple block randomisation with random variable block length. Main outcome measures: The primary outcome was eradication of P. aeruginosa at 3 months and remaining free of infection to 15 months. Secondary outcomes included time to reoccurrence, spirometry, anthropometrics, pulmonary exacerbations and hospitalisations. Primary analysis used intention to treat (powered for superiority). Safety analysis included patients who had received at least one dose of any of the study drugs. Cost-effectiveness analysis explored the cost per successful eradication and the cost per quality-adjusted life-year. Results: Between 5 October 2010 and 27 January 2017, 286 patients were randomised: 137 patients to intravenous antibiotics and 149 patients to oral antibiotics. The numbers of participants achieving the primary outcome were 55 out of 125 (44%) in the intravenous group and 68 out of 130 (52%) in the oral group. Participants randomised to the intravenous group were less likely to achieve the primary outcome; although the difference between groups was not statistically significant, the clinically important difference that the trial aimed to detect was not contained within the confidence interval (relative risk 0.84, 95% confidence interval 0.65 to 1.09; p = 0.184). Significantly fewer patients in the intravenous group (40/129, 31%) than in the oral group (61/136, 44.9%) were hospitalised in the 12 months following eradication treatment (relative risk 0.69, 95% confidence interval 0.5 to 0.95; p = 0.02). There were no clinically important differences in other secondary outcomes. There were 32 serious adverse events in 24 participants [intravenous: 10/126 (7.9%); oral: 14/146 (9.6%)]. Oral therapy led to reductions in costs compared with intravenous therapy (–£5938.50, 95% confidence interval –£7190.30 to –£4686.70). Intravenous therapy usually necessitated hospital admission, which accounted for a large part of this cost. Limitations: Only 15 out of the 286 participants recruited were adults – partly because of the smaller number of adult centres participating in the trial. The possibility that the trial participants may be different from the rest of the cystic fibrosis population and may have had a better clinical status, and so be more likely to agree to the uncertainty of trial participation, cannot be ruled out. Conclusions: Intravenous antibiotics did not achieve sustained eradication of P. aeruginosa in a greater proportion of cystic fibrosis patients. Although there were fewer hospitalisations in the intravenous group during follow-up, this confers no advantage over the oral therapy group, as intravenous eradication frequently requires hospitalisation. These results do not support the use of intravenous antibiotics to eradicate P. aeruginosa in cystic fibrosis. Future work: Future research studies should combine long-term follow-up with regimens to reduce reoccurrence after eradication. Trial registration: Current Controlled Trials ISRCTN02734162 and EudraCT 2009-012575-10. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 65. See the NIHR Journals Library website for further project information.

Activated charcoal was microencapsulated with Lactobacillus acidophilus 314 previously adapted for urea uptake. The creatinine removal capacity of this combination microcapsule was evaluated in-vitro in media simulating the small intestine. Results show that microcapsules containing both activated charcoal and L. acidophilus 314 demonstrated potential for decreasing creatinine. Interestingly, when co-encapsulating both activated charcoal and L. acidophilus 314 a smaller decrease in creatinine was observed than when encapsulating them separately. However, co-encapsulated microcapsules were more stable in various parts of the gastrointestinal system and survived longer in storage. These results suggest the feasibility of using microcapsules containing activated charcoal and probiotic bacteria as oral adjuvants for creatinine removal and provides a theoretical model for the use of these microcapsules to remove any unwanted metabolite.

Objective: This study aimed to compare the efficacy of Low-Intensity Extracorporeal Shockwave Therapy (Li-ESWT) and oral therapy combination compared to sole oral therapy for reducing symptoms in CP/CPPS patients. Material & Methods: A systematic search was conducted from the electronic database including PubMed, Clinicaltrial.gov, and Cochrane Library, published up to July 2020 following the PRISMA guideline. We screened RCTs with the inclusion criteria and assessed the quality with the Cochrane Risk of Bias tool. The primary outcome was the National Institute of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and subgroup analysis for triple therapy users was conducted to improve interpretability. The analysis was performed using Review Manager 5.3. Results: A total of 2 RCTs consisted of 91 CP/CPPS patients were analyzed. Pooled analysis showed that compared to the oral therapy only group, combination therapy had a significant lower NIH-CPSI total score at the endpoint of the treatment (MD -7.46, 95% CI -9.85 to -5.07, p

To assess preferences of women with ovarian cancer regarding features of available anti-cancer regimens for platinum-resistant, biomarker-positive disease, with an emphasis on oral PARP inhibitor and standard intravenous (IV) chemotherapy regimens. A discrete-choice-experiment preferences survey was designed, tested, and administered to women with ovarian cancer, with 11 pairs of treatment profiles defined using seven attributes (levels/ranges): regimen (oral daily, IV weekly, IV monthly); probability of progression-free (PFS) at 6 months (40%–60%); probability of PFS at 2 years (10%–20%); nausea (none, moderate); peripheral neuropathy (none, mild, moderate); memory problems (none, mild); and total out-of-pocket cost ($0 to $10,000). Of 123 participants, 38% had experienced recurrence, 25% were currently receiving chemotherapy, and 18% were currently taking a PARP inhibitor. Given attributes and levels, the relative importance weights (sum 100) were: 2-year PFS, 28; cost, 27; 6-month PFS, 19; neuropathy,14; memory problems, nausea, and regimen, all ≤5. To accept moderate neuropathy, participants required a 49% (versus 40%) chance of PFS at 6 months or 14% (versus 10%) chance at 2 years. Given a 3-way choice where PFS and cost were equal, 49% preferred a monthly IV regimen causing mild memory problems, 47% preferred an oral regimen causing moderate nausea, and 4% preferred a weekly IV regimen causing mild memory and mild neuropathy. These findings challenge the assumption that oral anti-cancer therapies are universally preferred by patients and demonstrate that there is no "one size fits all" regimen that is preferable to women with ovarian cancer when considering recurrence treatment regimens. • A survey of patient preferences for ovarian cancer recurrence regimens. • Progression-free survival (PFS) and personal cost drove treatment choice. • Patients did not prefer oral over intravenous recurrence regimens. [ABSTRACT FROM AUTHOR]

Opinion Statement: Intravenous administration of fluoropyrimidine-based chemotherapy has been the backbone of treatment in colorectal cancer (CRC) for decades. The availability of oral capecitabine has improved the tolerability and simplified combination schedules. In addition to capecitabine, several other oral drugs have proven efficacy, particularly in palliative treatment lines. Clinical guidelines describe several available third-line treatment options for metastatic CRC (mCRC), but few insights are provided to guide the selection and sequence. In this review, we describe the available evidence and most recent data concerning oral drugs with proven efficacy in CRC, including antiangiogenetic tyrosine kinase inhibitors (VEGFR TKIs), inhibitors blocking EGFR/Raf/MEK/ERK signaling pathway and modified fluoropyrimidine, and share recommendations and insights on selecting third-line oral therapies for mCRC in China. In general, third-line treatment options for mCRC are mainly regorafenib, fruquintinib, and chemo/targeted therapy reintroduction, while FTD/TPI was rarely used in China probably due to poor accessibility. Fruquintinib is preferred in patients with poor performance status (PS), elder age, and severe organ dysfunction, compared to regorafenib. New drugs of clinical trials were more recommended for the patients with BRAF mutant tumor, and those with good previous treatment efficacy tended to be recommended for chemo/targeted therapy reintroduction. The management of mCRC is evolving, and it must be emphasized that the consideration and recommendations presented here reflect current treatment practices in China and thus might change according to new clinical data as well as the availability of new oral drugs. [ABSTRACT FROM AUTHOR]

Inflammatory bowel diseases (IBDs) are chronic and disabling conditions that, uncontrolled, lead to irreversible bowel damage and associated comorbidities. Despite the new era of biological therapies, IBDs remain not curative. The treatment purpose is to induce endoscopic remission, reduce the progression of the disease and improve the quality of life. Optimal and early treatment could enable the prevention of their complications. Small molecules, administrated as oral agents, have the capacity of overcoming the limitations of biologic agents (i.e., parenteral administration, rapidity of action and primary and secondary non-responsiveness). Of special interest are results from the use of oral sphingosine 1-phosphate (S1P) receptor modulators (ozanimod, etrasimod, fingolimod and laquinimod), based on S1P activities to target lymphocyte recirculation in the mucosa, acting as immunosuppressive agents. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks. Cost-effectiveness studies and head-to-head trials are needed to better define their place in therapy. This review summarizes these emerging data published by PubMed and EMBASE databases and from ongoing clinical trials on the safety and efficacy of selectivity of S1P modulators in the treatment of IBD.