Extended Treatment Duration Research Articles

Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition.

The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.

Modernizing the assessment and reporting of adverse events in oncology clinical trials using complementary statistical approaches: a case study of the MOTIVATE trial.

The reporting of adverse events (AEs) is fundamental to characterize safety profiles of novel therapeutic drug classes, however, conventional analysis strategies are suboptimal tools for this task. We therefore attempted to contribute to the modernization of AE analysis by encompassing the dimension of time, the duration and the recurrent nature of AEs induced by these extended treatment durations. This paper presents and highlights the benefits of alternative approaches to modernize AE analysis based on the MOTIVATE prospective study modeling immune-related AEs (irAEs) in patients with solid tumors (regardless of the primary site) treated with immune checkpoint inhibitor irrespective of disease stage. The probability of presenting an irAE over time was estimated using the prevalence function. The time-to-onset (TTO) and the mean number of recurrent irAEs were also assessed. Among the 147 patients analyzed, 39.7% had a melanoma, 37.7% a non-small cell lung cancer (NSCLC) and 74.8% were treated for metastatic disease. Despite a higher proportion of melanoma patients presenting at least one irAE, the prevalence of irAEs was lower in melanoma than in NSCLC patients over time. TTO analysis showed that irAEs occurred earlier in NSCLC patients whereas melanoma patients experienced more recurrent irAEs over the long-term. The prevalence function of non-metastatic and metastatic patients revealed different long-term toxicity profiles. These alternative methodologies capture different toxicity patterns (time-to-onset, recurrent, acute episodic or long-term moderate AEs) and provide a more consistent safety assessment for new therapeutics, thereby assisting clinicians and health authorities in their therapeutic decision-making processes.

QSAR Modeling, Molecular Docking and ADMET Study of Aryl Fluorosulfate Derivatives as Potential Anti-TB Agents

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, stands as a global infectious disease presenting substantial public health challenges due to its high incidence and mortality rates. The prolonged use of conventional anti-TB therapies has led to the emergence of severe drug resistance in Mtb, resulting in extended treatment durations, increased costs, poor patient compliance, and reduced cure rates. This phenomenon has posed a significant burden on global TB prevention and control efforts, necessitating a shift in research focus toward the exploration of novel anti-TB drugs. In this context, utilizing QSAR modeling methods, our study systematically investigated the relationship between the chemical structures of 36 aryl fluorosulfate derivatives and their inhibitory activity against Mtb. Robust and predictive Topomer CoMFA and HQSAR models were developed, featuring Topomer CoMFA model parameters: q 2 = 0.659, r 2 = 0.969, F = 102.877, N = 6, SEE = 0.138; HQSAR model parameters: q 2 = 0.705, r 2 = 0.873, SEE = 0.264, HL = 199, N = 4. Leveraging these models, structural modifications were applied to the compounds using the ZINC15 database, leading to the successful design and screening of three novel compounds with desirable inhibitory activity. Molecular docking and ADMET performance prediction results indicated that these three new compounds exhibit strong binding capabilities and promising pharmaceutical potential. This study provides valuable insights and research directions for the development of aryl fluorosulfate derivatives as potential agents for tuberculosis treatment and as novel drugs.

Deacidification of concentrated cranberry juice by electrodialysis with bipolar membranes: A feasibility and comprehensive study

Electrodialysis with bipolar membranes (EDBM) recently shown promising outcomes as a novel green technology to deacidify cranberry juice without altering its polyphenolic compounds, responsible for many health benefits. The performance of EDBM depends on many factors, including the concentration of the treated solution. While previous research only deacidified cranberry juice by EDBM with concentration of 8°B, the present study aimed to assess the physicochemical attributes of more concentrated juices and the effect of using specific ones (5°B, 15°B, 25°B and 35°B) during EDBM on deacidification and electrodialytic parameters evolution. Optimal juice characteristics for EDBM use (viscosity, conductivity) were exhibited at 25°B. The 4 selected juice concentrations were successfully deacidified by 39.0 ± 2.5 % but with significantly different process times (from 46 ± 2 min to 471 ± 16 min). Extended treatment duration led to a slight loss in anthocyanins and proanthocyanidins, likely due to increased polyphenols-membranes interactions, which contributed to system resistance growth. However, the reduction in citric (32 ± 3 %) and malic (61 ± 4 %) acids remained consistent, regardless of the juice concentration. This work confirmed the feasibility of producing a concentrated and deacidified cranberry juice by EDBM, that can represent a great potential to the functional food market.

Predictors and Management of Inadequate Response to JAK Inhibitors in Alopecia Areata.

Alopecia areata is a common autoimmune disorder characterized by non-scarring hair loss on the scalp or other hair-bearing surface. In recent years, Janus kinase (JAK) inhibitors have shown promise in the treatment of alopecia areata by disrupting the signaling pathways involved in immune-mediated hair follicle damage. However, some patients with alopecia areata exhibit insufficient responses to JAK inhibitors. This review aims to explore the predictive factors for poor responses to JAK inhibitors in patients with alopecia areata and to discuss alternative treatment strategies in such cases. Patients with a longer duration of the current episode and higher baseline severity are at an increased risk of inadequate JAK inhibitor responses. Oral administration rather than topical application, and extended treatment durations, correlate with a favorable response. Notably, the poor response to JAK inhibitors in alopecia areata may be related to the amount and functional depletion of regulatory T cells resulting from an augmented T helper-2-type immune response. For patients with poor responses to JAK inhibitors, treatment adjustments may include increasing the dosage, extending the treatment duration, combination therapies, or switching to alternative JAK inhibitors. For patients with atopic comorbidities or psychological problems, it is important to select corresponding treatment options to optimize patient outcomes. Further research is needed to establish more reliable predictors and improve overall patient care.

Clinical Benefits of DaxibotulinumtoxinA for Injection: Beyond Glabellar Line Effacement?

Botulinum toxin type A (BoNTA) is standard of care for glabellar lines ameliorization. DaxibotulinumtoxinA for Injection (DAXI) is a new BoNTA with a unique formulation representing the latest advancement in BoNTA technology. There is an unmet need for patients to understand the full potential of BoNTA treatment and new technologies. To update clinical data supporting the use of DAXI for glabellar lines within the context of clinical experience. A narrative review of the literature and summary of clinical experience with DAXI. The DAXI clinical trial program reflects clinical experience post-FDA approval, with DAXI demonstrating rapid onset, high patient response rates, and extended treatment duration versus conventional BoNTAs. Clinical observations suggest that DAXI has limited diffusion from the injection site, enabling more localized control of muscle activity and greater improvements in wrinkle severity. DAXI enables practitioners to exert greater finesse in their injections and in predicting changes to eyebrow shape and position and achieve improvement in skin quality. Advances in BoNTA technology can provide patients with greater options for treatment outcomes. The potential for enhanced localized effects with DAXI may contribute to more precise and targeted effects on muscle activity and additional aesthetic benefits to patients.

Enhancing spatial memory and pattern separation: Long-term effects of stimulant treatment in individuals with ADHD

This study explores the under-researched domain of long-term stimulant treatment in children and adolescents diagnosed with attention deficit hyperactivity disorder (ADHD). The necessity for extended treatment duration, often accompanied by safety concerns and side effects leading to treatment discontinuation, underscores the significance of this investigation. Concurrently, comparative studies have revealed adverse impacts on vulnerable regions within the hippocampal formation, accompanied by behavioral perturbations. We employed computerized tests and virtual reality to assess spatial memory, pattern separation, and object recognition memory in a cohort of children diagnosed with ADHD receiving stimulant treatment. We compared their performance to a group of neurotypical peers. Our findings indicate that the ADHD group exhibited a lower performance in spatial memory, pattern separation, and object recognition memory than ND group. Intriguingly, a positive relationship emerged between the duration of stimulant treatment and performance in these variables. Notably, this improvement was not immediate to MPH treatment but becomes significant after 24 months of treatment. In contrast to previous comparative investigations, our study did not reveal a detrimental impact on spatial navigation, object recognition memory, or pattern separation, despite the known interplay of these cognitive processes with the hippocampal formation. These results shed new light on the nuanced effects of stimulant treatment in ADHD, underscoring the need for a more comprehensive understanding of long-term treatment outcomes.

The prognosis of pancreatic neuroendocrine tumors according to the WHO 2017 classification: The multi-center experience in Taiwan.

87 Background: The occurrence of pancreatic neuroendocrine tumors (PanNETs) remains infrequent, there is an upward trend in their diagnosis. Our retrospective study, conducted in Taiwan, focuses on exploring the interplay between clinical characteristics, treatment modalities, and prognosis in PanNET cases. Particularly, we aim to assess the implications of the updated WHO classification system on prognosis. Methods: We conducted a retrospective analysis of 176 PanNET cases from Chang Gung Medical Foundation, encompassing Linkou, Taoyuan, and Tucheng Hospitals, spanning the years 2009 to 2022. Pathology reports for all cases were reevaluated by pathologists according to the WHO 2017 classifications. Clinical features and overall survival outcomes were documented. Additionally, we examined the prognosis of distinct subgroups categorized by the WHO 2017 classification and their respective treatments. Results: The 5-year survival rate for all patients in the cohort stood at 58.7%. Among these, individuals diagnosed with NET G1 exhibited the highest survival rate (n = 78, 83.1%), followed by those with NET G2 (n = 57, 55.0%), NET G3 (n = 25, 14.6%), and NEC (n = 16, 9.4%). Univariate analysis highlighted several significant prognostic factors, including age, absence of symptoms at diagnosis, tumor size, lymph node involvement, distant metastasis, higher Ki-67 index, and cellular morphology. Comparative analysis between the WHO 2017 and WHO 2010 classifications revealed both systems as significant independent predictors of overall survival in PanNET cases. Notably, the 95% confidence interval for the WHO 2017 classification (2.892–9.703) showed a slight improvement in prognostic precision compared to the WHO 2010 classification (3.696–10.067). Under the WHO 2010 classification, NET G3 and NEC were combined, with NEC presenting higher rates of distant metastases, lymph node involvement, and Ki-67 index. Further investigation revealed that patients receiving somatostatin analogs, chemotherapy, or targeted therapy exhibited improved survival rates, particularly notable in NET G3 and NEC subgroups. Furthermore, NEC patients displayed extended treatment durations and higher objective response rates to first-line chemotherapy compared to the NET G3 group. Conclusions: Our retrospective analysis has illuminated the interrelation between prognostic factors and the overall survival rate. Furthermore, the updated WHO 2017 classification elucidates the distinctions between G3 and NEC, thus influencing the selection of clinical interventions.

Pulsed corona discharge: an advanced treatment method for antibiotic-contaminated water

Water pollution is one of the most significant problems of the current century. With the increase in medicine availability and use, pharmaceutical pollutants such as antibiotics become more prevalent in natural environments with potentially negative impact. In this study, a pulsed corona discharge was investigated as a possible treatment method of water contaminated with amoxicillin (AMX). Two system configurations were used: plasma and plasma-ozonation. In order to better grasp the effect of system and water matrix on degradation, different pulse widths, solutions pH and conductivity values, as well as the nature of the dissolved salts were investigated. Decreasing the pulse width from 300 ns to 106 ns (full width at half maximum) led to almost a two-fold increase in energy yield at 50% pollutant removal, and the addition of the ozonation reactor resulted six times enhancement in efficiency. While the water matrix had little impact on AMX degradation, the buffering capacity of carbonates has proven beneficial by preventing pH decrease during treatment. Under optimum conditions, the energy yield was 57 g kWh−1 at 93% removal of AMX in tap water. A number of 26 potential degradation products have been identified, resulting from hydroxylation of the benzene ring, oxidation of the thioester and amine groups, hydrolysis, and cleavage of the benzene, β-lactam and thiazole rings, along with fragmentation of the resulting compounds. All but seven degradation intermediates are completely removed by extending treatment duration to 60 min and the persistent ones are less toxic than the parent compound.

Long COVID and lung thromboembolism in young adults

Long-term COVID-19 (Long COVID) and pulmonary thromboembolism (PTE) significantly challenge healthcare, especially in young adults who are typically at lower risk for such severe outcomes. This review explores the complex relationship between long-term COVID and PTE, focusing on the pathophysiological mechanisms, diagnostic challenges, and therapeutic approaches. Persistent inflammation and immune dysregulation associated with long-term COVID-19 contribute to this demographic's increased thrombotic risk. The symptom overlaps between long-term COVID and PTE complicate the accuracy and timeliness of diagnoses, highlighting the necessity for improved diagnostic strategies. Findings emphasize the need for anticoagulation protocols tailored to the specific clinical presentations of Long COVID patients and suggest that extended treatment durations may be beneficial. The potential of genetic and biomarker research to identify individuals at heightened risk of thrombotic complications is discussed. The review calls for a multidisciplinary approach that integrates medical and psychosocial interventions to manage the long-term effects of COVID-19 effectively. As the pandemic evolves, advancing our understanding and adapting healthcare strategies to these insights are crucial for developing effective clinical practices. This is essential for addressing the immediate health impacts and reducing the broader socioeconomic burdens associated with long-term COVID and PTE in young adults.

Cognitive Analytic Therapy (CAT) in borderline personality disorder: a case report on the efficacy of longer treatment duration

ABSTRACT This article presents a case report on the use of Cognitive Analytic Therapy (CAT) in treating a patient with features of Borderline Personality Disorder (BPD) over an extended treatment duration. The case report highlights the effectiveness of CAT in addressing complex and entrenched issues and emphasises the use of the Sequential Diagrammatic Reformulation (SDR) and Multiple Self State model as key therapeutic tools. The findings demonstrate the benefits of longer treatment duration in CAT for individuals with features of BPD and underscore the importance of tailoring treatment to individual needs.

Assessment and Treatment of Vaginitis.

Vaginitis is the presenting symptom at millions of office visits each year in the United States. Although treatment of sporadic cases is often straightforward, recurrent cases present both diagnostic and treatment challenges. Molecular diagnostic tests are likely superior to in-office microscopy for most clinicians and most cases. In both recurrent bacterial vaginosis and recurrent vulvovaginal candidiasis, national treatment guidelines recommend an extended treatment duration with one of the first-line agents. In cases in which such treatment is not successful, vaginal boric acid is likely the cheapest and easiest alternative option. New antifungal medications offer additional but limited treatment options. Probiotics are not recommended for prevention of vulvovaginal candidiasis; however, vaginal products containing Lactobacillus crispatus may have promise for recurrent bacterial vaginosis. Trichomoniasis should be treated with a 1-week course of metronidazole; this is the only sexually transmitted infection for which treatment recommendations vary by sex. In cases in which patients do not respond to initial treatment, the diagnosis should be reconsidered, and other potential causes such as desquamative inflammatory vaginitis, genitourinary syndrome of menopause, or vulvodynia should be considered.

Efficacies of omadacycline + amikacin + imipenem and an all-oral regimen omadacycline + clofazimine + linezolid in a mouse model of M. abscessus lung disease.

Treatment outcomes for Mycobacteroides abscessus (Mab, also known as Mycobacterium abscessus) disease are still unsatisfactory, mainly due to issues with drug toxicity, tolerability, and efficacy. Treating Mab disease is challenging due to its high baseline antibiotic resistance, initial requirement for intravenous therapy, and poor medication tolerance. Omadacycline, a new tetracycline, is active against Mab. Since any new antibiotic effective against Mab is expected to be used in combination with other antibiotics, we evaluated the efficacy of two triple-drug combinations comprising omadacycline, omadacycline + amikacin + imipenem, and omadacycline + clofazimine + linezolid against two contemporary Mab clinical isolates in a mouse model of Mab lung disease. Antibiotic administration was initiated 1-week post-infection and was given daily, with Mab burden in the lungs at treatment completion serving as the endpoint. Omadacycline alone moderately reduced Mab levels and maintained better health in mice compared to untreated ones, which typically suffered from the infection. The omadacycline + clofazimine + linezolid combination showed immediate bactericidal activity and enhanced efficacy over 6 weeks, particularly against the more resistant strain (M9507). However, the clofazimine + linezolid combination lacked early bactericidal activity. When combined with amikacin and imipenem, omadacycline did not improve the regimen's effectiveness over 4 weeks of treatment. Our study showed that omadacycline + clofazimine + linezolid exhibited significant bactericidal activity over an extended treatment duration. However, adding omadacycline to amikacin and imipenem did not improve regimen effectiveness against the evaluated clinical isolates within 4 weeks. Further research in Mab disease patients is needed to determine the most effective omadacycline-containing regimen.IMPORTANCEMycobacteroides abscessus is a common environmental bacterium that causes infections in people with compromised lung function, including those with bronchiectasis, cystic fibrosis, chronic obstructive pulmonary disease, and weakened immune systems, especially among older individuals. Treating M. abscessus disease is challenging due to the limited effectiveness and toxicity of current antibiotics, which often require prolonged use. Omadacycline, a new antibiotic, shows promise against M. abscessus. Using a mouse model that mimics M. abscessus disease in humans, we studied the effectiveness of including omadacycline with recommended antibiotics. Adding omadacycline to clofazimine and linezolid significantly improved treatment outcomes, rapidly clearing the bacteria from the lungs and maintaining effectiveness throughout. This oral combination is convenient for patients. However, adding omadacycline to amikacin and imipenem did not improve treatment effectiveness within 4 weeks. Further study with M. abscessus patients is necessary to optimize omadacycline-based treatment strategies for this disease.

Comparative Evaluation of Activated and Nonactivated Microbubbles on the Efficacy of Bleaching Agents.

Intracoronal bleaching serves as a conservative option for nonvital teeth that exhibit discoloration.Hydrogen peroxide (H2O2) is frequently utilized in bleaching processes owing to its capability to produce free radicals.The main drawbacks of the currently available bleaching agents are the occurrence of cervical resorption and the multiple dental visits to achieve the desired result. Therefore, in our study, to address the limitations associated with cervical resorption and extended treatment duration for badly stained teeth, an attempt was made to incorporate a whitening agent (35% H2O2) with microbubbles. This study aimed tocompareandevaluatetheeffect ofactivated and nonactivated microbubbles on the efficacy of bleaching agents. Forty-five human central incisors were collected and divided into three groups:Group I (HP), H2O2 plain(n= 15) (Control); Group II (HPM), H2O2-infused microbubbles without ultrasonic activation (n= 15) (experimental group); and Group III (HPMU), H2O2-infused microbubbles with ultrasonic activation (n= 15) (experimental group).The crowns were artificially stained. Microbubbles containing 35% H2O2were generated using the probe sonication method.The bleaching agent H2O2 plain (0.04 mL) was syringed into the pulp chamber in group I, while H2O2-infused microbubbles (0.04 mL) were syringed into group II and group III. Group III was further activated ultrasonically. The evaluation of color shade differences was conducted using the Vita Lumin shade guide at three time points: baseline, day 7, and day 14. Data regarding color change using Vita shade were investigated for normality using theKolmogorov Smirnov test and assessed a non-normal distribution.Intergroup comparisons at each particular time interval (baseline, day 7, and day 14) were analyzed using the Kruskal-Wallis H test followed by multiple pairwise comparisons using the Adjusted Bonferroni post hoc test. Intragroup comparisons between different time intervals were analyzed using related samples from Friedman's test followed by multiple pairwise comparisons using the post hoc Dunn test. The level of statistical significance was determined at P< 0.05. There was no statistical difference in the baseline values of all three groups. Group I (HP) exhibited an average increase of three Vita Lumin shade tabs on day 7 and day 14, respectively, whereasGroup II (HPM)exhibited an average increase of six and four Vita Lumin shade tabs on day 7 and day 14, respectively, and Group III (HPMU)exhibited an average increase of 10 and 3 Vita Lumin shade tabs on day 7 and day 14, respectively. Microbubbles containing H2O2 were more efficient and faster than plain H2O2 for bleaching, and the efficacy of bleaching was enhanced when activated using ultrasonic technology.

Discrepancy index, treatment complexity index and objective Grading system: correlation between parameters, indices and implications for treatment

Abstract Objectives An assessment of orthodontic treatment duration and results allows for measurable outcomes, goal-setting, and the establishment of patient management standards. It is important information that can be utilised for educational purposes in an orthodontic postgraduate program. The aim of this study was to determine correlations of the parameters within and between the Objective Grading System (OGS), Discrepancy Index (DI) and Treatment Complexity Index (TCI) and identify those factors associated with treatment outcomes and duration. Materials and methods This retrospective cohort study involved a consecutive sampling of 242 pre- and post-treatment patient records from the postgraduate orthodontic clinic between 2013 and 2017. The cases were assessed using the DI, OGS, and TCI pre-treatment. Treatment outcomes were assessed using the OGS. Spearman’s Rank Correlation Coefficients were computed within and between the indices. Multiple and logistic regressions were used to evaluate associations between treatment outcomes and duration, respectively. Results Within DI, significant correlations (p &lt; 0.05) were observed between overjet-overbite, overjet-occlusal relationship, overjet-crowding, overbite-anterior open bite, overbite-crowding, anterior open bite-lateral open bite, anterior open bite-crowding, lingual posterior cross bite-crowding. Within pre-OGS, significant correlations (p &lt; 0.05) were observed between alignment-marginal ridge, alignment-occlusal relationship, alignment-root angulation, overjet-interproximal contact, marginal ridge-buccolingual inclination, marginal ridge-overjet, marginal ridge-occlusal contact, marginal ridge-occlusal relationship, overjet-occlusal contact, overjet-occlusal relationship, overjet-root angulation, occlusal relationship-root angulation, interproximal contact-root angulation. Within TCI, functional appliance correlated with orthognathic surgery (p &lt; 0.001), rapid palatal expansion (RPE) (p = 0.005) and multidisciplinary collaboration (p = 0.001). Pre-OGS correlated with DI (p &lt; 0.001) and TCI (p = 0.026). Cephalometric (p = 0.002) and other conditions (p = 0.031) were associated with treatment outcomes. RPE was associated with extended treatment duration (p = 0.014). Conclusions DI, OGS, and TCI exhibited weak correlations within and between indices. Cephalometric values, clinical conditions, and RPE use should be carefully considered during treatment planning.

Antimicrobial susceptibility and virulence gene analysis of Shigella species causing dysentery in Iranian children: Implications for fluroquinolone resistance

Shigella species significantly impact global health due to their role in diarrheal diseases. A 2019–2022 cross-sectional study on 432 stool samples from pediatric patients in Mashhad, Iran, identified Shigella spp. and tested their susceptibility to 12 antimicrobials by the disk diffusion method. The presence of virulence factors, namely ipaH, virA, stx1, and stx2, as well as plasmid-mediated quinolone resistance (PMQR) genes, including qnrA, qnrB, qnrC, qnrD, and qnrS, were ascertained through the utilization of polymerase chain reaction techniques. Sequencing of 15 isolates detected mutations within quinolone resistance-determining regions (QRDRs) at the gyrA and parC genes, indicating fluoroquinolone (FQ) resistance. 19.2 % (83/432) of stool samples contained Shigella, primarily S. sonnei (77.1 %), followed by S. flexneri (21.6 %) and S. boydii (1.2 %). Most isolates were from children under five (55.4 %). All strains had the ipaH gene, lacked stx1 and stx2, and 86.7 % had virA. High resistance was noted for ampicillin and tetracycline (84.3 % each), trimethoprim-sulfamethoxazole (81.9 %), and azithromycin (60.2 %). 87.1 % of isolates were multidrug-resistant (MDR). The most common PMQR genes were qnrA and qnrS (41 % each). The qnrD gene, prevalent in 36.1 % of cases, is reported in Iran for the first time. The most common PMQR profile was qnrADS (15.7 %). Resistance to nalidixic acid and ciprofloxacin was 45.8 % and 12 %, respectively. The Shigella isolates exhibited mutations in the gyrA (at codons 83, 87, and 211) and parC (at codons 80, 84, 93, 126, 128, 129, and 132) genes. The D87Y mutation in the gyrA gene was the most common in Shigella isolates, occurring in 73 % of cases. The F93S and L132T mutations in the parC gene were unique to this study. Empirical FQ therapy in patients infected with MDR Shigella, possessing PMQR determinants and/or mutations in the QRDRs of gyrA and parC, may escalate the risks of secondary diseases, extended treatment duration, therapeutic failure, and resistance spread. Consequently, the necessity for continuous surveillance and genetic testing to detect FQ-resistant Shigella strains is of paramount importance.

Outcome measures of brainwave entrainment using delta wave stimulation in individuals with tinnitus having normal hearing sensitivity.

The current study aimed to evaluate the efficacy of delta frequency binaural beats stimulation in treatment of individuals with tinnitus having normal hearing sensitivity. Twenty-four individuals who reported bothersome tinnitus in the presence of clinically normal hearing were grouped into two (I and II). The group was provided with delta frequency binaural beats and II was provided with white noise stimulation (both of 20min duration) for 30days. Post 30days, the re-assessment of tinnitus handicap, depression, anxiety, and quality of life parameters were performed and compared with that of pre-treatment scores. A considerable reduction of tinnitus handicap scores, depression and anxiety levels were observed for both the groups, except for the quality-of-life parameters. However, few of the participants showed limited or negligible improvement post-treatment. On comparison of reduction of scores observed across the groups, there was a higher reduction of scores observed for group I when compared to group II. The current study was an initial attempt to study the efficacy of binaural beats in treatment of individuals with tinnitus having normal hearing. Apart from a few individuals, the delta wave stimulation acted as a helpful tool in improving tinnitus borne distress symptoms in such patients with normal hearing.The results of the present study put forward the scope of adapting binaural beats stimulation for the treatment of individuals presenting with tinnitus having normal hearing sensitivity. This technique could be adopted into clinical practice after extensive research involving an extended treatment duration on a larger population.

Permeable Reactive Barrier Remediation Technique Using Carbonized Food Waste in Ground Contaminated with Combined Cu and Pb

In recent years, with the escalation of food waste generation, stringent legal constraints on landfill usage and incineration have necessitated the exploration of alternative disposal methods, augmenting interest in diverse recycling strategies. Notably, carbonized food waste (CFW), a byproduct of food waste carbonization, has emerged as an efficacious adsorbent for pollutant removal. This study focuses on the application of in situ remediation techniques, specifically electrokinetic (EK) remediation combined with enhancers, to decontaminate soil afflicted with single or multiple heavy metals. The utilization of a permeable reactive barrier (PRB) infused with CFW aims to mitigate secondary environmental repercussions, including the propagation of contaminants in soil and groundwater. Experiments were conducted on clay samples contaminated with copper, lead, or a combination thereof. Observations revealed that the current density peaked during the initial 1–2 days of the experiment, experienced a resurgence post-electrode exchange, and subsequently diminished. The efficacy of metal removal was predominantly pronounced for copper, with remediation rates ranging from 85% to 92% in singly contaminated samples and 75% to 89% in dually contaminated samples after a 10-day treatment period, incorporating an electrode exchange on the eighth day. Conversely, the efficacy of lead removal was markedly lower, with rates of 0.6% to 33% in singly contaminated samples and 14% to 25% in combined contamination scenarios, suggesting the necessity for extended treatment durations. The post-experimental moisture content indicated successful enhancer injection. Additionally, pH measurements affirmed that heavy metals migrated effectively within the sample matrix, facilitated by the EK phenomenon after the electrode exchange. This study highlights the potential of CFW within PRBs for the remediation of heavy metal-contaminated soils, although the removal efficiencies between different metals is variable, emphasizing the need for tailored approaches in the treatment of lead-contaminated environments.

Gastrointestinal safety evaluation of semaglutide for the treatment of type 2 diabetes mellitus: A meta-analysis.

Semaglutide, as an innovative weekly formulation, has attracted much attention. Nevertheless, the predominant occurrence of gastrointestinal adverse events (GIAEs) poses a noteworthy challenge linked to the use of this medication, substantially affecting its clinical applicability and the overall well-being of patients. Therefore, this systematic review aims to comprehensively discuss the GIAEs, providing a basis for clinical therapeutic decisions. We systematically searched 4 independent databases for randomized controlled trials investigating the application of semaglutide in managing type 2 diabetes mellitus. The search period spanned from the inception of the databases to December 2023. We conducted a comprehensive meta-analysis, employing Review Manager 5.4.1 software, to systematically analyze and evaluate potential biases. Our primary emphasis was on assessing the gastrointestinal safety profile of semaglutide. The outcomes unveiled a noteworthy rise in the collective occurrence of GIAEs across all dosage groups of semaglutide in comparison with the control group (P < .05). Upon further analysis, it was observed that semaglutide showed a heightened occurrence of GIAEs in contrast to the placebo. However, statistically significant distinction was not observed when compared to the reduction of conventional doses or the transition to other types of glucagon-like peptide-1 receptor agonist. Additionally, an extended treatment duration with semaglutide (>30 weeks) demonstrated an association with a certain degree of decrease in the incidence of gastrointestinal events. Funnel plot assessment for publication bias demonstrated high-quality inclusion of studies with no apparent publication bias. The frequency of GIAEs in using semaglutide was observed to be elevated in comparison to the control group. However, it was comparable to other glucagon-like peptide-1 receptor agonist or low-dose treatment regimens. Additionally, an extended treatment duration played a role in decreasing the frequency of GIAEs. These findings provide valuable insights for clinical practice. Nonetheless, further research is crucial to explore supplementary data indicators, informing clinical practices and better serving the interests of patients.

Amikacin Liposome Inhalation Suspension (ALIS) as part of the initial regimen in the treatment of non-tuberculous mycobacteria (NTM) treatment

Managing non-tuberculous mycobacterial (NTM) lung disease poses challenges due to the extended treatment duration and frequent occurrence of adverse effects. Amikacin Liposome Inhalation Suspension (ALIS) is a liposomal form of amikacin, delivered through inhalation directly to the lungs. Recently published guidelines now recommend the use of (ALIS) as a component of the treatment regimen for Mycobacterium avium complex (MAC) lung disease in cases of refractory disease. However, no data exist supporting its inclusion in the initial regimen. In this case report, we present a patient with a newly diagnosed M. intracellulare infection and extensive bilateral disease who received ALIS due to the precarious use of parenteral amikacin. A 64-year-old female patient, with impaired kidney function due to kidney cancer and nephrectomy presented with cough and malaise over the last three months. The CT scan performed demonstrated multiple bilateral nodules and infiltrates, as well as bronchiectasis. A bronchoscopy was conducted and M.intracellulare was isolated from the bronchoalveolar lavage. Given the extensive nature of the disease, even in the absence of a cavity and given the impaired kidney function, the patient was administered a therapy regimen including azithromycin, rifampicin, ethambutol, and ALIS. The patient benefited the most of the treatment in terms of clinical, microbiological and imaging aspects while avoiding serious adverse effects due to amikacin. It is necessary to always consider the best treatment for the patient even beyond established guidelines in order to achieve the best outcome. ALIS is a promising new treatment that needs to be studied further.