Microbial regulation of serotonin: A boost for drug delivery.

Nanoparticle drug carriers play an important role in facilitating efficient targeted drug delivery, i.e., improving treatment success and reducing drug costs and side effects. However, the mobility of nanoparticle drug carriers poses a challenge in designing drug delivery systems. Moreover, healing results critically depend on the rate and time duration of drug absorption. Therefore, in this paper, we aim to design a controlled-release drug delivery system with a mobile drug carrier that minimizes the total amount of released drugs while ensuring a desired rate of drug absorption during a prescribed time period. We model the mobile drug carrier as a mobile transmitter, the targeted diseased cells as an absorbing receiver, and the channel between the transceivers as a time-variant channel since the carrier mobility results in a time-variant absorption rate of the drug molecules. Based on this, we develop a molecular communication (MC) framework to design the controlled-release drug delivery system. In particular, we develop new analytical expressions for the mean, variance, probability density function, and cumulative distribution function of the channel impulse response (CIR). Equipped with the statistical analysis of the CIR, we design and evaluate the performance of the controlled-release drug delivery system. Numerical results show significant savings in the amount of released drugs compared to a constant-release rate design and reveal the necessity of accounting for drug carrier mobility for reliable drug delivery.

INTRODUCTION: Diabetes Mellitus (DM) often leads to diabetic neuropathy (DN), particularly Diabetic Peripheral Neuropathy (DPN), causing significant pain and discomfort. Despite available pharmacological treatments, many patients remain untreated or experience intolerable side effects. METHODS: A comprehensive search strategy was implemented through March 26, 2024, across five databases (PubMed, Scopus, WOS, Embase, and Cochrane CENTRAL), identifying studies relevant to SCC and PDN. Eligibility criteria included all clinical trials reporting teh safey and efficacy of SCS in PDN patients. The screening and data extraction were done by two independent reviewers. Risk of bias assessment was done by ROBINS-I or RoB 2.0 tool. Statistical analysis involved narrative synthesis and meta-analysis. Subgroup analyses and leave-one-out analyses were performed. RESULTS: The mean difference (MD) in pain intensity between the SCS and best medical therapy (BMT) groups after six months was -4.82 (95% CI: [-6.42, -3.22], p < 0.00001), favoring the SCS group. Treatment success, defined as achieving =50% pain relief, was significantly higher in the SCS group with a risk difference (RD) of 0.59 (95% CI: [0.33, 0.85], p < 0.00001) compared to BMT group. Additionally, SCS led to a significant improvement in quality of life measures compared to BMT group, with an MD of 0.16 (95% CI: [0.10, 0.23], p < 0.00001) for EQ-5D utility index and an MD of 15.29 (95% CI: [4.51, 26.07], p = 0.005) for self-reported health. Adverse events related to SCS implantation were generally low. CONCLUSIONS: SCS shows promise as an effective treatment option for painful PDN, offering significant pain relief, improved treatment success, and enhanced quality of life. Despite some heterogeneity and limitations in the current evidence. Further high-quality trials, including comparisons between different SCS modalities, are recommended to validate these findings and optimize treatment approaches for painful PDN patients.

0019 NUTRITION AND SCHIZOPHRENIA

Pharmacological treatment of eating disorders, comorbid mental health problems, malnutrition and physical health consequences

Dry eye disease (DED) is a multifactorial disease of the ocular surface characterized by loss of homeostasis of the tear film and accompanied by ocular signs and symptoms such as corneal and conjunctival damage, patient discomfort, and visual disturbance. The prevalence of DED ranges from 5%−33%. Patients with DED may have a reduced quality of life due to their discomfort and visual disturbances. The multifactorial nature of DED requires a multi-targeted treatment approach to address the signs and symptoms. Treatment for DED should follow a step-wise approach beginning with education, dietary modification, and lid and lash hygiene, and progressing to pharmacologic and nonpharmacologic interventions. Ocular lubricants, a mainstay of DED therapy, provide temporary symptomatic relief for the patient, but do not address the underlying pathophysiology. Some currently available pharmacologic treatments that address the underlying pathophysiology of DED may have a delay of 3−6 months in the onset of therapeutic effect; however, these treatment options may also have tolerability issues. These challenges highlight the need for newer pharmacologic treatments with an earlier onset of observable clinical effect and the potential for improved tolerability profile. Patient education is vital to DED management and should convey the complex and chronic nature of DED. It is important for the eye care practitioner to set realistic expectations with the patient when managing DED to help improve treatment success. This helps the patient understand the need for ongoing treatment and that results will likely not be seen immediately. This review covers the current management of DED, focusing on pharmacologic management, and offers recommendations for the practitioner to help facilitate realistic patient expectations for the treatment of DED.

Medical treatment for multidrug-resistant (MDR)-tuberculosis is complex, toxic, and associated with poor outcomes. Surgical lung resection may be used as an adjunct to medical therapy, with the intent of reducing bacterial burden and improving cure rates. We conducted an individual patient data metaanalysis to evaluate the effectiveness of surgery as adjunctive therapy for MDR-tuberculosis. Individual patient data, was obtained from the authors of 26 cohort studies, identified from 3 systematic reviews of MDR-tuberculosis treatment. Data included the clinical characteristics and medical and surgical therapy of each patient. Primary analyses compared treatment success (cure and completion) to a combined outcome of failure, relapse, or death. The effects of all forms of resection surgery, pneumonectomy, and partial lung resection were evaluated. A total of 4238 patients from 18 surgical studies and 2193 patients from 8 nonsurgical studies were included. Pulmonary resection surgery was performed on 478 patients. Partial lung resection surgery was associated with improved treatment success (adjusted odds ratio [aOR], 3.0; 95% confidence interval [CI], 1.5-5.9; I(2)R, 11.8%), but pneumonectomy was not (aOR, 1.1; 95% CI, .6-2.3; I(2)R, 13.2%). Treatment success was more likely when surgery was performed after culture conversion than before conversion (aOR, 2.6; 95% CI, 0.9-7.1; I(2)R, 0.2%). Partial lung resection, but not pneumonectomy, was associated with improved treatment success among patients with MDR-tuberculosis. Although improved outcomes may reflect patient selection, partial lung resection surgery after culture conversion may improve treatment outcomes in patients who receive optimal medical therapy.

Recent studies have expanded the evidence on novel and existing non-pharmacological treatments for paediatric functional constipation (FC). This study aimed to systematically review the efficacy and safety of non-pharmacological therapies for FC in children. PubMed, MEDLINE, Embase, PsycINFO, Cochrane Library and trial registries were searched from inception to March 2025. Randomised controlled trials (RCTs), including children (0-18 years) with FC treated with non-pharmacological interventions compared with placebo, no treatment or other interventions, were included. Primary outcomes were treatment success, defecation frequency and withdrawals due to adverse events. Dual data extraction and appraisal was conducted. Certainty was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). 93 RCTs comprising 7787 children (50.4% female) were included investigating dietary, psycho-educational, physiotherapeutic interventions, various complementary and complementary medicine interventions, and electrical stimulation. A substantial part of the therapies provided evidence that was of very low certainty, meaning no conclusions could be drawn. Abdominal transcutaneous electrical stimulation plus pelvic floor muscle exercises (PFME) may improve treatment success and defecation frequency compared with PFME alone (risk ratio (RR): 1.75 (95%CI 1.25 to 2.44) and mean differences (MD): 1.85 (95%CI 1.28 to 2.43), moderate certainty). Percutaneous tibial nerve stimulation plus PFME leads to more treatment success (RR: 1.73 (95%CI 1.08 to 2.77), low certainty) and greater defecation frequency (MD: 1.82 (95%CI 0.82 to 2.82), moderate certainty). Behavioural therapy plus polyethylene glycol may not improve treatment success (RR: 0.83 (95%CI 0.62 to 1.12), low certainty) and probably reduces defecation frequency (MD: -1.80 (95%CI -2.88 to -0.72), moderate certainty). Imprecise data, poor reporting and substantial heterogeneity led to downgrading in GRADE assessments. Some non-pharmacological treatment options for children with FC show beneficial effects, and these may be considered in the management of children. Future trials should aim to improve methodological rigour. CRD42023416891.

Fellowship Training in Arthroplasty Improves Treatment Success of Debridement, Antibiotics, and Implant Retention for Periprosthetic Knee Infections

Crossing Barriers From blood-to-brain and academia-to-industry

Techniques that increase the permeability of the cell membrane and transfer drugs or genes to cells have been actively developed as effective therapeutic modalities. Also, in line with the development of these drug delivery techniques, the establishment of tools to verify the techniques at the cellular level is strongly required. In this study, we demonstrated an optical imaging platform integrated with an ultrasound application system to verify the feasibility of safe and efficient drug delivery through the cell membrane using ultrasound-microbubble cavitation. To examine the potential of the platform, fluorescence images of both Fura-2 AM and propidium iodide (PI) to measure calcium flux changes and intracellular PI delivery, respectively, during and after the ultrasound-microbubble cavitation in the cervical cancer cell were acquired. Using the optical imaging platform, we determined that calcium flux increased immediately after the ultrasound-microbubble cavitation and were restored to normal levels, and fluorescence signals from intracellular PI increased gradually after the cavitation. The results acquired by the platform indicated that ultrasound-microbubble cavitation can deliver PI into the cervical cancer cell without irreversible damage of the cell membrane. The application of an additional fluorescent imaging module and high-speed imaging modalities can provide further improvement of the performance of this platform. Also, as additional studies in ultrasound instrumentations to measure real-time cavitation signals progress, we believe that the ultrasound-microbubble cavitation-based sonoporation can be employed for safe and efficient drug and gene delivery to various cancer cells.

ObjectivesBehaviour management strategies involving pharmacological or non-pharmacological interventions during dental procedures should be considered to attain safe and successful treatment outcomes. This study compared the frequencies of use and the completeness of treatment with these interventions.MethodsA total of 1725 dental records of patients up to 18 years old, who were treated in the King Abdulaziz Medical City in Jeddah City from October 2018 to June 2019, were used in this retrospective, cross-sectional study. Inferential analysis, Chi-square test, Kruskal–Wallis test, and regression model were used in the data analysis.ResultsAbout two-thirds of the patients were treated with attendant non-pharmacological interventions, while one-third, with pharmacological interventions. The application of General Anesthesia (GA) was the most frequently used intervention. Restorative procedures and extractions were done in higher frequencies with pharmacological interventions. Treatments with space maintainers and orthodontic appliances were carried out in higher frequencies with non-pharmacological strategies. The choice of intervention was significantly influenced by the systemic conditions of the patients. Patients treated with non-pharmacological intervention comprised the dominant type of patients, because they required treatments with less pain. Those treated with GA needed restorative treatments and extractions, or treatments that involve pain, but these treatments had higher frequencies of being completed.ConclusionsThe treatments with pharmacological intervention through GA have higher frequencies of being completed, compared to those with non-pharmacological interventions. Factors, such as age, potential to complete the treatment, and the type of dental treatment applied, influence the choice of treatment intervention.

BACKGROUND: TB notifications in Latin American prisons have more than doubled over the past two decades; however, treatment outcomes and their determinants among incarcerated individuals in this region are not well understood.METHODS: Newly diagnosed drug-susceptible TB cases reported to Brazil´s Information System for Notifiable Diseases (Sistema de Informação de Agravos de Notificação, SINAN) between January 2015 and December 2017 were included. Multivariate logistic regression was used to assess socio-economic and clinical factors associated with treatment success among incarcerated individuals.RESULTS: Incarcerated individuals (n = 17,776) had greater treatment success than non-incarcerated individuals (n = 160,728; 82.2% vs. 75.1%; P < 0.0001), including after adjusting for demographic and clinical risk factors (adjusted odds ratio aOR 1.27, 95% CI 1.19-1.34). These differences were partially mediated by increased use of directly observed therapy among incarcerated individuals (DOT) (61% vs. 47%; P < 0.001), which was associated with greater efficacy in the incarcerated population (aOR 2.56 vs. aOR 2.17; P < 0.001). DOT was associated with improved treatment success among incarcerated subpopulations at elevated risk of poor outcomes.CONCLUSION: TB treatment success among incarcerated individuals in Brazil is higher than non-incarcerated individuals, but both fall below WHO targets. Expanding the use of DOT and services for socially and medically vulnerable individuals may improve outcomes in carceral settings.

BackgroundUndernutrition is associated with unfavourable treatment outcomes among people with drug-resistant tuberculosis (DRTB). Factors influencing the treatment outcomes among undernourished people with DRTB are not well characterised. The aim of this study was to determine factors associated with treatment success among undernourished people with DRTB in Uganda.MethodsWe analysed data from a retrospective cohort of people with DRTB from 16 treatment sites in Uganda. We included participants with a pre-treatment body mass index (BMI) of <18.5 kilograms/meters2 (kg/m2). Participants were categorised as having mild (BMI of 18.5–17 kg/m2), moderate (BMI of 16.9–16.0 kg/m2) or severe (BMI of <16.0 kg/m2) undernutrition. We performed logistic regression analysis to determine factors associated with treatment success.ResultsAmong 473 people with DRTB, 276 (58.4%) were undernourished (BMI < 18.5 Kg/m2) and were included in the study. Of these, 92 (33.3%) had mild, 69 (25.0%) had moderate and 115 (41.7%) had severe undernutrition. The overall treatment success rate (TSR) for the undernourished was 71.4% (n = 197). Although the TSR was similar among participants with mild (71.7%), moderate (78.3%) and severe (67.0%) undernutrition (p = 0.258), all treatment failure cases (n =6) were among participants with severe undernutrition (p = 0.010). Cigarette smoking (odds ratio (OR) = 0.19, 95% CI 0.07–0.47, p < 0.001), urban residence (OR = 0.31, 95% CI 0.14–0.70, p = 0.005) and moderate (OR = 0.14, 95% CI 0.06–0.35, p < 0.001) and severe anaemia (OR = 0.06, 95% CI 0.01–0.29, p = 0.001) were associated with lower odds of treatment success.ConclusionMost undernourished people with DRTB have severe undernutrition. Smoking and anaemia are modifiable factors which upon appropriate intervention could improve treatment success. The effect of urban residence on the TSR needs to be evaluated further.

Chapter 11 - Carbon dots as carriers for the development of controlled drug and gene delivery systems

Drug delivery is defined as mechanisms to introduce pharmaceutical compounds to human in order to achieve therapeutic effects. We have come a long way since chewing medicinal plants and inhaling soot from medicinal substance were the only form of drug delivery. These approaches lacked consistency and uniformity of drug delivery. Since then there has been a continuous effort to discover and improve drug delivery routes and drug delivery systems. Conventional drug delivery system includes drug delivery via oral route as solutions, suspensions, emulsions, and tablets. Some are delivered systemically via injections and intravenous application. Medications are applied topically as lotions and gels. Nasal route is used for drug delivery to lungs by inhalers and nebulizers. Apart from antibiotics, vaccines, and chemical compounds, modern medicine includes recombinant DNA, insulin, interferon, interleukin, erythropoietin, tissue plasminogen activator, and other peptides and macromolecules as drugs that require efficient drug delivery systems. Traditional drug delivery systems suffer from various limitations such as low bioavailability, intolerance, toxic side effects, reduced plasma half-life, higher concentration, and low efficacy. The hydrophilic drugs have difficulty in passing through the cell membrane. Systemically delivered drugs reach all the organs irrespective of the affected organ. This causes toxic side effects on the healthy cells. The drugs tend to degrade fast in the plasma so higher doses of drug are required and hence it becomes toxic with reduced efficacy and are expensive. The biological barriers exclude the drug from reaching the affected cells and tissues. Efficient drug targeting can improve drug delivery efficacy, reduce side effects, and lower treatment cost. Hence, much effort is given on the development of novel carriers that would meet the requirement of drug delivery systems. The main areas of research are to increase bioavailability of the drugs, increase plasma half-life, and target to specific organs or cells. This would result in lowering the dose, which would also lower drug-induced toxicity, protect bystander cells and organs from adverse side effects, and reduce medical expenses. In this chapter, we will discuss the biological barriers, advances in drug delivery systems, drug targeting, and their application in diseases.