Daily Regimen Research Articles

A novice perspective on exercise as a cause of diseases in contra-indication with Vyayama mentioned in Ayurveda

Fitness is the most crucial parts of everyones life, in current era each human being is very well known to the fact of being fit and healthy with various means namely adopting moderation food habits, maintaining 24 hrs cycle and amongst all the attempts most trendy is physical exercise. In Ayurveda every detail of life is mentioned according to its need in one’s life, its indication, contra-indication and importance, but often we humans tend to violate the ground rules in quest of achieving great. Ayurveda emphasizes maintaining health through structured daily routines, including dinacharya (daily regimen), ratricharya (night regimen), and ritucharya (seasonal routine), which are essential for disease prevention and overall well-being. A key component of dinacharya is vyayama (physical exercise), considered fundamental for health maintenance and disease prevention. Ayurvedic texts highlight that appropriate physical activity positively impacts not only the body but also the mind (Mana), emotions, senses (Indriyas), and spirit (Aatma). When practiced correctly, vyayama enhances overall well-being and maximizes health benefits. However, improper execution can lead to health issues. This review article aims to provide an overview of vyayama according to Ayurvedic principles, detailing its effects on the body and necessary precautions for safe practice.

South African Parents' and Grandparents' Perspectives on the Acceptability of Implant Delivery of Treatment to Young Children with HIV.

Children living with HIV (CLWH) face unique challenges with adherence to antiretroviral therapy. In South Africa, just over a third of children receiving antiretroviral therapy are virally suppressed. Long-acting, subcutaneous implants may improve outcomes in CLWH compared to current daily oral dosing regimens. Qualitative in-depth interviews and focus group discussions (FGD) were conducted with 50 caregivers of CLHW in Johannesburg, South Africa. Interviews and FGDs were audio-recorded and transcribed. Data were coded and analyzed using Dedoose v9 software and a thematic approach. Caregivers had generally positive impressions of the pediatric HIV treatment implant. They emphasized the advantages of a long-acting and discreet treatment option for CLWH. Cited advantages were perceived to have widespread impact on CLWH, their caregivers, and other social dynamics. Caregivers raised some concerns or uncertainties about the potential efficacy, side effects and safety of the implant. Future clinical testing and outreach efforts may address such concerns and mitigate potential misinformation about implants. This study indicates the need to develop long-acting, discreet, safe, and efficacious HIV treatment options for young children.

Azacitidine in combination with shortened venetoclax treatment cycles in patients with acute myeloid leukemia.

The combination of venetoclax with hypomethylating agents is currently the standard of care for elderly patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Despite its favorable efficacy, clinical use is often associated with post-remission cytopenia, frequently necessitating treatment delays and dose modifications. This study aims to evaluate the efficacy and safety of shortened venetoclax treatment durations. A multicenter analysis was conducted involving 20 adult AML patients receiving venetoclax (7 or 14 days with 9 and 11 patients, respectively) combined with 5-azacitidine (5-7 days) between 2021 and 2024. The cohort included patients from four German academic centers all treated in first line. Outcome measures included bone marrow response, transfusion dependence, overall survival (OS) and progression-free survival (PFS). Median age was 73.5 years, with 70% of patients having secondary AML. Adverse molecular risk was observed in 75% of patients. The overall response rate (ORR) was 100%, with a composite complete remission rate of 78%. No significant differences in response rates were observed between the 7-day and 14-day venetoclax regimens. Median OS for the cohort was 15 months. Infection-related complications were observed in 55% of patients, with severe sepsis in 20% of cases. In this cohort, shortened venetoclax regimens demonstrated efficacy comparable to standard treatment protocols, with a potential reduction in hematologic toxicity. These findings support the individualization of treatment regimens to optimize clinical outcomes while potentially minimizing adverse effects.

Real-world analysis of safety, tolerability, and adherence to nirmatrelvir-ritonavir (paxlovid) in primary care COVID-19 outpatients.

This retrospective cross-sectional study aims to evaluate the safety, tolerability, and adherence of patients prescribed Nirmatrelvir-ritonavir (Paxlovid) in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Data were collected from the Paxlovid pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. This study analysed data from 415 category 2 COVID-19 patients aged ≥ 18years. The primary and secondary outcomes included the assessment of patient demographics, Paxlovid dosing, current medication, changes in drug regimen, adherence, and adverse drug reactions (ADR). Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite this, the ADRs were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not to comply with the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Paxlovid demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

6778 Visual Presentations for Adherence Risk Management In Patients Receiving Recombinant Human Growth Hormone Therapy

Abstract Disclosure: P. van Dommelen: Consulting Fee; Self; PvD has a consultancy agreement with Merck KGaA, Darmstadt, Germany. F. Michelis: Employee; Self; FL is an employee of Ares Trading SA, an affiliate of Merck KGaA. L. Arnaud: Employee; Self; LA is an employee of Ares Trading SA, an affiliate of Merck KGaA. S. Loche: Advisory Board Member; Self; SL has received advisory board fees from Merck KGaA, Darmstadt, Germany. Consulting Fee; Self; SL has received consultancy fees from Merck KGaA, Darmstadt, Germany. Speaker; Self; SL has received lecture fees from Merck KGaA, Darmstadt, Germany. E. Koledova: Employee; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Stock Owner; Self; EK holds shares in Merck KGaA, Darmstadt, Germany. Background: A data-driven clinical decision support system based on visual presentations for adherence risk management can support patients receiving recombinant human growth hormone (r-hGH) treatment. Our focus is on examining adherence patterns during the first 6 weeks of treatment, with a particular emphasis on the days of the week, the variability in injection timings and the summer holiday. Our aim is to assess whether these early patterns can serve as indicators for predicting adherence in the subsequent 7-12 weeks of treatment. Data and Methods: Adherence data between March-November 2023 were extracted from the newly launched third generation of easypod™ device (EP3) and GrowZen Connect Next ecosystem. EP3 is the only connected device that delivers r-hGH and monitors real-time adherence to therapy. EP3 was perceived by health care professionals as more intuitive, comfortable, user-friendly, simpler, and easier to use than previous EP2. Patients with age 2-18 years at treatment start, a 7-day regimen and complete adherence data available between 1-12 weeks of treatment were selected. Data about sex, age at start treatment, as well as adherence, classified as high (≥95%) versus low/medium <95%), standard deviation (SD) of adherence (%), log (to adjust for skewness) of the interquartile range (IQR) of the timing of injection throughout the day, median timing of the injection after midnight, and ≥50% versus <50% of the injections fall in the summer period (July-August) aggregated by day over the first 6 weeks of treatment were included in a generalized linear mixed model with adherence between 7-12 weeks as outcome. Results: In total, data for 232 patients (124 boys and 108 girls, median (Q25-Q75) age at treatment start was 10.5 (7.6-12.3)) were available. The model showed no difference in effect of adherence rates during Monday-Thursday. We, therefore, aggregated the data by weekday (Monday-Thursday) versus weekend day (Friday-Sunday, Friday was included due to the common practice of administering injections during the evening). Adherence, SD of adherence, IQR of timing of injections, and injections falling in summer were significant (p<0.05) predictors of adherence during a weekday and weekend between 7-12 weeks. Areas under the curves were both 0.96 during the weekday and weekend. Conclusions: Our research shows that adherence and timing of injections, as well as taking into account the summer holidays, can predict future adherence accurately. Visual presentations showing aggregated adherence rates and variation of timing of injections by days of the week, as well as highlighting the summer periods may improve adherence risk management and timely support. Presentation: 6/3/2024

6818 Adherence Risk Management in Patients on Recombinant Human Growth Hormone Therapy, With Traffic Light Alerting Systems Tailored for Both Weekday and Weekend Adherence

Abstract Disclosure: S. Loche: Advisory Board Member; Self; SL has received advisory board fees from Merck KGaA, Darmstadt, Germany. Consulting Fee; Self; SL has received consultancy fees from Merck KGaA, Darmstadt, Germany. Speaker; Self; SL has received lecture fees from Merck KGaA, Darmstadt, Germany. P. van Dommelen: Consulting Fee; Self; PvD has a consultancy agreement with Merck KGaA, Darmstadt, Germany. V. Tornincasa: Employee; Self; VT is an employee of Ares Trading SA, an affiliate of Merck KGaA. L. Arnaud: Employee; Self; LA is an employee of Ares Trading SA, an affiliate of Merck KGaA. E. Koledova: Employee; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Stock Owner; Self; EK is an employee of Merck KGaA,Darmstadt, Germany. Background: The integration of data-driven strategies, such as clustering analysis with an alerting system, empowers healthcare professionals with actionable insights. In this study, we focused on clustering adherence patterns during the weekdays and weekends in the first 12 weeks of treatment. Our aim is to develop a data-driven clinical decision support system based on "traffic light" visualizations addressing adherence challenges during both weekdays and weekends in patients receiving Recombinant Human Growth Hormone Therapy. Data and Methods: Adherence data between March-November 2023 were extracted from the newly launched third generation of easypod™ device (EP3) and GrowZen Connect Next ecosystem. EP3 is the only connected device that delivers r-hGH and monitors real-time adherence to therapy. EP3 was perceived by health care professionals as more intuitive, comfortable, user-friendly, simpler, and easier to use than previous EP2. Patients with age 2-18 years at treatment start, a 7-day regimen and complete adherence data available between 1-12 weeks of treatment were selected. Patients’ adherence to therapy was represented using mean and standard deviation (SD) of adherence (%) and the interquartile range (IQR) of the timing of injections throughout the day in minutes aggregated by weekday (Monday-Thursday) and weekend day (Friday-Sunday). Cluster analysis was used to categorize adherence patterns using a Gaussian mixture model. Following a traffic lights-inspired visualization approach, the algorithm was set to create three clusters: high (green), medium (yellow), and low adherence (red). The area under the receiver operating characteristic curve (AUC-ROC) was used to find optimum thresholds for independent traffic lights. Results: Data for 232 patients (124 boys and 108 girls, median (Q25-Q75) age at treatment start was 10.5 (7.6-12.3)) were available. The most appropriate traffic light used the SD of adherence during the weekend, with an AUC-ROC value of 0.87. For the weekday, adherence-based traffic lights using optimum thresholds were >98% (SD<10.2), 88-98% (SD:10.2-22.8) and <88% (SD>22.8) for high, medium, and low adherence, respectively. For IQR of the timing of injections throughout the weekday, optimum thresholds were <38, 38-70 and >70 (min). For the weekend, optimum thresholds were >96% (SD<7.7), 86-96% (SD:7.7-21.5) and <86% (SD>21.5). For IQR of the timing of injections throughout the weekend, optimum thresholds were <56, 56-84 and >84 (min). Conclusions: Our research indicates that implementing a practical data-driven alert system, utilizing our proposed traffic-light coding, would empower healthcare practitioners to monitor patients' adherence to growth hormone therapy comprehensively. By understanding patient behavior during the weekdays and weekend, healthcare practitioners can tailor interventions for improved treatment outcomes. Presentation: 6/3/2024

12438 Developing A Natural Language Processing Algorithm To Identify Insulin Pump Users Using Unstructured Clinical Notes From The Electronic Health Record

Abstract Disclosure: E.M. Everett: None. R. Tiu: None. B. Zhu: None. T. Moin: None. A.T. Bui: None. Background: Insulin pumps (pump) have many benefits to patients with type 1 diabetes compared to management with multiple daily injection regimens. Unfortunately, disparities exist in pump therapy access and use, particularly in racial-ethnic minoritized groups, those of lower socioeconomic status or limited English proficiency. Given that these groups are underrepresented in pump clinical trials, evaluating data from real-world populations such as those from large health systems is critical to improve technology use in these groups that also experience disparities in diabetes outcomes. Unfortunately, it is very challenging to identify diabetes technology users using electronic health record data due to the underutilization of ICD and procedure codes for pump use and the documentation of pump use in unstructured form in clinical notes, which is more difficult to extract outside of manual chart review. Consequently, a novel approach is needed to capture this population on a large scale. We aim to develop an algorithm using the machine learning method natural language processing (NLP), to identify these technology users and non-users in health systems, which would allow us to study pump use in real-world settings. Methods: To develop the algorithm, we performed chart review and cataloged documentation styles (keywords, phrases) indicating pump use from 88 clinical notes of adults with type 1 diabetes, authored by physicians and nurse educators in UCLA endocrinology clinics from 2014-2022. After reaching saturation for documentation styles, we used a series of regular expressions (Regex) to encode the algorithm, including code to negate phrases that may lead to false positives. Results: We tested the algorithm performance in an 85 note sample that included 59 pump users and 26 non-users. The algorithm detected 56/59 pump users and 26/26 non-pump users, yielding a sensitivity of 95% (95%CI 87-99%), a specificity of 100% (95%CI 86-100%) specificity, a positive predictive value of 100% (95%CI 94-100%), and a negative predictive value of 90% (95%CI 74-96%). Conversely, an approach using ICD and procedure codes only identified 17/59 pump users with a sensitivity of 28% (95%CI 18-42%), specificity of 100% (95%CI 87-00%), positive predictive value of 100% (95%CI 81-100%), and negative predictive value of 38% (95%CI 35-42%). Incrementally, the NLP algorithm identified ∼70% more pump users than the approach using billing codes. Conclusion: NLP is a promising approach to identify pump users using unstructured electronic health record data. Next steps include testing the current algorithm in a larger sample of clinical notes, revising the algorithm as needed. The final algorithm will be used to understand patterns and disparities of pump prescribing over time and will be leveraged as a recruitment tool to identify potentially eligible patients for future studies aimed at addressing pump disparities. Presentation: 6/3/2024

12564 A Rare Case Of Pembrolizumab Induced Secondary Adrenal Insufficiency

Abstract Disclosure: L. Escano Volquez: None. P. Desai: None. Pembrolizumab is an immune check-point inhibitor that blocks the PD1 receptor and is currently used in the treatment of a vast variety of malignancies. Despite adrenal insufficiency (AI) already being documented as a rare but potential side effect, its diagnosis is usually delayed due to vague presentation, increasing the risk of deleterious outcomes. We present a case of secondary AI while on pembrolizumab in which diagnosis was delayed due to unspecific clinical picture.This is a 66-year-old male who presented to the hospital with decreased appetite, nausea and generalized weakness. Patient was seen a month prior with similar symptoms which were thought to be secondary to poor oral intake in the setting of underlying malignancy. Medical history remarkable for squamous cell carcinoma of the skin with recent lung metastasis for which he was started on pembrolizumab a year ago. On arrival to the emergency department, patient was hypertensive with BP 144/68 mmHg, HR 88, and RR 15. Orthostatic vitals were positive. Physical examination otherwise unremarkable. Laboratory tests revealed mild hypernatremia of 147, potassium of 4.7, chloride 108, HCO3 18, anion gap 21, BUN 33, elevated creatinine 1.62 and elevated beta-hydroxybutyrate 5.4. EKG revealed sinus rhythm. Patient was admitted for further evaluation of orthostasis and starvation ketosis. Initial management included IV fluids and Midodrine. However, patient continued to have episodes of orthostatic hypotension. Lack of improvement of symptoms led to further workup which revealed low AM cortisol of 1.0 and a low ACTH level <3.0 pg/ml, concerning for secondary adrenal insufficiency. Patient was administered Solu-Medrol 40 mg IV before being transitioned to a daily hydrocortisone regimen with subsequent improvement of symptoms. Pembrolizumab induced AI is a very rare event. It is estimated that the incidence approaches 1% and symptoms can develop at any time throughout treatment. Despite its low incidence, it can be life-threatening if not diagnosed and treated promptly. However, given its very heterogeneous and vague clinical presentation, a prompt diagnosis can be difficult. The clinical course of our patient and subsequent resolution of symptoms after appropriate treatment was started, supports the diagnosis of pembrolizumab induced adrenal insufficiency after a year of initiating treatment. This patient had prior hospitalizations and office visits with symptoms that are usually already present in individuals with underlying malignancy, which resulted in underestimation of his symptoms. This case highlights the importance of always considering AI as a potential adverse effect of immune check-point inhibitors. This will ensure a prompt diagnosis and treatment of an endocrine disorder that could otherwise lead to deleterious outcomes if left untreated. Presentation: 6/1/2024

Natural Skin Care Regimen Improves Clinical Parameters and Quality of Life in Children with Atopic Dermatitis

Background: Atopic dermatitis (AD) is a prevalent, chronic inflammatory skin disorder, characterized by xerosis, itching and recurrent eczematous lesions. The condition also has major psychosocial implications for patients and their families. A daily skincare regimen of gentle cleansing and moisturization is an important part of atopic dermatitis therapy. Objective: This study evaluated the tolerability and efficacy of a nature-based shampoo/wash and moisturizer in children with mild to moderate atopic dermatitis Methods: This open-label study involved 23 children (6 months – 13 years) with atopic dermatitis. A daily skin care regimen of nature-based shampoo/wash and moisturizer was used for 4 weeks. The primary endpoint was tolerability assessed through clinical grading of erythema, dryness and roughness. The study pediatrician graded the eczema condition using the Eczema Area and Severity Index (EASI), and assessments of stratum corneum hydration and transepidermal water loss were performed before and after treatment. Parent/guardian completed two validated quality of life questionnaires. Results: Twenty children completed the study. Clinical evaluations showed significant improvement in subjects’ atopic disease with daily use of nature-based regimen. Significant reduction in dryness and roughness was observed, indicating that both products were well-tolerated. Moisture content and transepidermal water loss measurements showed directional improvements in skin barrier function. Parent/guardian reported significant improvements in quality-of-life assessments. Conclusions: The study demonstrated that nature-based skin care regimen was well tolerated and improved quality of life and skin condition in children with atopic dermatitis and can be used either alone or in adjunction with traditional treatment for disease control.

Dietary astragalin confers protection against lipopolysaccharide-induced intestinal mucosal barrier damage through mitigating inflammation and modulating intestinal microbiota.

The intestinal mucosal barrier (IMB) damage is intricately linked with the onset of numerous intestinal diseases. Astragalin (AS), a flavonoid present in numerous edible plants, exhibits notable antioxidant and anti-inflammatory properties, demonstrating a promising impact on certain intestinal ailments. In this study, our objective was to investigate the protective effects of AS and elucidate the underlying mechanisms by which it mitigates lipopolysaccharide (LPS)-induced damage to the IMB in mice. During the experimental period, mice were subjected to a 7-day regimen of AS treatment, followed by LPS injection to induce IMB damage. Subsequently, a comprehensive evaluation of relevant biological indicators was conducted, including intestinal pathological analysis, serum inflammatory factors, intestinal tight junction proteins, and intestinal microbiota composition. Our results suggested that AS treatment significantly bolstered IMB function. This was evidenced by the enhanced morphology of the small intestine and the elevated expression of tight junction proteins, including ZO-1 and Claudin-1, in addition to increased levels of MUC2 mucin. Moreover, the administration of AS demonstrated a mitigating effect on intestinal inflammation, as indicated by the reduced plasma concentrations of pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α. Furthermore, AS treatment exerted a positive influence on the composition of the gut microbiota, primarily by augmenting the relative abundance of beneficial bacteria (including Lachnospiracea and Lactobacillus murinus), while simultaneously reducing the prevalence of the harmful bacterium Mucispirillum schaedleri. AS mitigates LPS-induced IMB damage via mitigating inflammation and modulating intestinal microbiota.

The Effectiveness and Safety of Remdesivir Use in COVID-19 Patients with Neutropenia: A Retrospective Cohort Study

Background: The COVID-19 pandemic poses severe risks for immunocompromised patients, especially those with neutropenia due to chemotherapy. This study evaluates the safety and effectiveness of remdesivir use in COVID-19 patients with neutropenia. Methods: This retrospective study used the Chang Gung Research Database (CGRD) and extracted data from 98,763 patients with COVID-19 diagnosed between April 2021 and September 2022. The patients were divided into groups based on their remdesivir use and the presence of neutropenia. The adverse effects of remdesivir and their outcomes were analyzed after propensity score matching. Results: We compared common adverse effects of remdesivir in neutropenic patients before and after a 5-day regimen. A slight decrease in heart rate was observed but lacked clinical significance. There were no significant differences observed in hemoglobin, liver function tests, and blood glucose levels. After propensity score matching of COVID-19 patients with neutropenia according to gender, age, dexamethasone use, oxygen use, MASCC score, and WHO ordinal scale, no significant differences were found in length of stay, intubation rate, or ICU admission rate between the matched patients. Conclusions: Our study found remdesivir to be safe for COVID-19 patients with neutropenia, with no common adverse reactions observed. However, its effectiveness for these patients remains uncertain.

Comparing laboratory and online settings: equivalence in training and transfer effects for training task-order coordination processes.

The literature on dual-task training suggests reductions in task-coordination costs with extensive practice, yet such regimens are resource-intensive. This study investigates the feasibility of online assessments for cognitive training studies by comparing training and transfer effects on task-order coordination (TOC) skills in laboratory versus online settings. We conducted a 5-day training regimen including pre-and post-test. Sixty-two participants completed training either in our laboratory or online via Pavlovia. They were assigned to one of two training order conditions, either practicing two visual-manual tasks in a dual-task situation with fixed task order or with random task order. Performance metrics included reaction time (RT) and error rates for trained and untrained tasks to assess TOC costs before and after the training. Data from both setting conditions (laboratory vs. online) were compared. Firstly, data of both settings revealed training-order specific training and transfer effects for TOC costs on RT level. Random task order training improved TOC for trained and untrained tasks, whereas fixed order training did not. Secondly, cross-setting analyses, both frequentists and Bayesian, confirmed these effects and revealed no reliable impact of setting on outcomes. This research carries two significant implications. Our findings demonstrate the acquisition of task-order coordination skills, extending prior research on improving task-coordination in dual-task situations. Additionally, the robust effects for such improvements were independent of specific tasks and setting (whether investigated online or in the laboratory), supporting the use of online testing in cognitive training regimens for resource savings without compromising quality.

The effects of AG1® supplementation on the gut microbiome of healthy adults: a randomized, double-blind, placebo-controlled clinical trial.

This study aimed to examine the effect of a commercially available multi-ingredient powder (AG1Ⓡ) on the gut microbiome and assess the impact of AG1Ⓡ on GI tolerability and other clinical safety markers in healthy men and women. Using a double-blind, randomized, two-arm, placebo-controlled, parallel design, we examined a 4-week daily supplementation regimen of AG1Ⓡ vs. placebo (PL). Fifteen men and 15 women provided stool samples for microbiome analysis, questionnaires for digestive quality of life (DQLQ), and completed visual analog scales (VAS) and Bristol stool charts to assess stool consistency and bowel frequency before and after the 4-week intervention. Participant's blood work (CBC, CMP, and lipid panel) was also assessed before and after the 4-week intervention. Alpha diversity was determined by Shannon and Chao1 index scores and evaluated by a two-way ANOVA, beta diversity in taxonomic abundances and functional pathways was visualized using partial least squares-discriminant analyses and statistically evaluated by PERMANOVA. To identify key biomarkers, specific feature differences in taxonomic relative abundance and normalized functional pathway counts were analyzed by linear discriminant analysis (LDA) effect size (LEfSe). Questionnaires, clinical safety markers, and hemodynamics were evaluated by mixed factorial ANOVAs with repeated measures. This study was registered on clinicaltrials.gov (NCT06181214). AG1Ⓡ supplementation enriched two probiotic taxa (Lactobacillus acidophilus and Bifidobacterium bifidum) that likely stem from the probiotics species that exist in the product, as well as L. lactis CH_LC01 and Acetatifactor sp900066565 ASM1486575v1 while reducing Clostridium sp000435835. Regarding community function, AG1Ⓡ showed an enrichment of two functional pathways while diminishing none. Alternatively, the PL enriched six, but diminished five functional pathways. Neither treatment negatively impacted the digestive quality of life via DQLQ, bowel frequency via VAS, or stool consistency via VAS and Bristol. However, there may have been a greater improvement in the DQLQ score (+62.5%, p = 0.058, d = 0.73) after four weeks of AG1Ⓡ supplementation compared to a reduction (-50%) in PL. Furthermore, AG1Ⓡ did not significantly alter clinical safety markers following supplementation providing evidence for its safety profile. AG1Ⓡ can be consumed safely by healthy adults over four weeks with a potential beneficial impact in their digestive symptom quality of life.

Diagnostic Challenges and Management of Non-Odontogenic Toothache: A Case of Unilateral Pansinusitis Mimicking Dental Pain

This case report details the diagnostic challenge and subsequent management of a 38-year-old male patient who presented with severe, sharp, and non-localized pain in the right maxillary distal area. Initial¬ly unresponsive to non-steroidal anti-inflammatory drugs and antibiotics, the patient’s symptoms deviat¬ed from typical odontogenic pain characteristics. Comprehensive dental examinations revealed minimal pathologies, challenging initial assumptions of dental-origin pain. Advanced diagnostic imaging, including Orthopantomography and Cone Beam Computed Tomography (CBCT), was pivotal in identifying unilat¬eral pansinusitis, with notable obstruction in the maxillary, ethmoid, and frontal sinuses. Further microbi¬ological analysis confirmed a Staphylococcus aureus and anaerobic infection, refocusing the diagnosis to a non-odontogenic source. The patient underwent a targeted 14-day complex antibiotic regimen, supple¬mented with local treatments including Nasonex nasal spray and saline nasal irrigations. This integrative approach resulted in marked symptom improvement and was instrumental in the patient’s recovery. This case highlights the critical need for thorough evaluation in distinguishing between odontogenic and non-od¬ontogenic sources of orofacial pain, ensuring accurate diagnosis and effective treatment.

Intraperitoneal daptomycin dosing for peritonitis may be inadequate: a Monte Carlo simulation approach to optimize dosing and outcomes

A two-compartmental mathematical pharmacokinetic model with first-order elimination of patients receiving CAPD of 4 exchanges for 6 h with 2 L of dialysate used in each cycle was developed to predict daptomycin disposition in 120 h of therapy. The pharmacodynamic target was plasma AUC/MIC equal to or greater than 666. The dose that achieved at least 90% of the probability of target attainment was defined as an optimal dose. Administering intraperitoneal 300 mg daily for 1 exchange daily regimen would be sufficient to treat peritonitis with S. aureus infection with MICs of 0.25 mg/L in patients undergoing CAPD. A higher dosage may be required for infections with a higher minimum inhibitory concentration. Pharmacodynamic targets and MICs significantly contributed to daptomycin doses in this setting. Clinical validation of our recommendations is recommended.

Exploring perspectives of children and young people with type 1 diabetes in laos: moving beyond twice daily insulin to multiple daily regimens"

Exploring perspectives of children and young people with type 1 diabetes in laos: moving beyond twice daily insulin to multiple daily regimens"

Study on the clinical efficacy of 14-day vonoprazan-based triple regimen in obese patients with Helicobacter pylori infection

The effectiveness of vonoprazan (VPZ)-based regimens in enhancing Helicobacter pylori (HP) eradication rates is promising. This study evaluated the clinical efficacy of 14-day VPZ-based triple therapy in obese patients infected with HP. A total of 200 obese patients with gastric disorders, confirmed to be HP-positive via gastroscopy and the 13C urea breath test, were retrospectively analyzed. Among them, 118 patients received the 14-day VPZ-based triple regimen (Study group), while 82 patients were treated with the traditional 14-day bismuth-containing proton pump inhibitor-based quadruple regimen (Control group). Baseline characteristics, pretreatment inflammatory indicators, lipid profiles, and gastrointestinal function indicators recorded. The two groups were compared for treatment efficacy, HP eradication rate, gastrointestinal function improvement, and incidence of adverse reactions. The Study group demonstrated a higher overall effective rate compared to the Control group, particularly in HP-strong positive obese patients. No significant differences were observed between the two groups for HP-positive obese patients in terms of total effective rate, HP eradication rate, gastrointestinal function improvement, or adverse reactions incidence. In conclusion, the 14-day VPZ-based triple regimen exhibited superior therapeutic efficacy, higher HP eradication rates, enhanced gastrointestinal function, and reduced adverse reactions in HP-strong positive obese patients, indicating improved overall efficacy and safety.

Fluoxetine attenuates the anxiolytic effects of the probiotic VSL#3 in a stress-vulnerable genetic line of aves in the chick social-separation stress test, a dual screening assay

Anxiety disorders represent one of the most common and debilitating illnesses worldwide. However, the development of novel therapeutics for anxiety disorders has lagged compared to other mental illnesses. A growing body of research suggests the gut microbiota plays a role in the etiopathology of anxiety disorders and may, therefore, serve as a novel target for their treatment through the use of probiotics. The use of dietary supplements like probiotics is increasing and their interaction with pharmacotherapies is not well understood. Utilizing the chick social-separation stress test, the primary aim of this study was to evaluate the commercially-available multi-strain probiotic found in VSL#3 for potential anxiolytic-like and/or antidepressant-like effects in the stress-vulnerable Black Australorp genetic line. A secondary aim was to evaluate the interaction between probiotics and the SSRI fluoxetine. Animals were treated with either saline, probiotics, fluoxetine, or probiotics + fluoxetine for 8 days prior to exposure to a 90-min isolation stressor that produces both a panic-like (i.e., anxiety-like) state followed by a state of behavioral despair (i.e., depression-like). The 8-day probiotic regimen produced anxiolytic-like effects but did not attenuate behavioral despair. Fluoxetine failed to significantly alter behavior in either of the two phases. Moreover, the combination of fluoxetine with probiotics attenuated the anxiolytic-like effects of probiotics. The fluoxetine + probiotics combination had no effect on behavioral despair. The results of the current study align with other preclinical studies and some clinical trials suggesting probiotics may offer beneficial effects on anxiety. Investigations examining the anxiolytic-like mechanism of probiotics are needed before any conclusions can be made. Additionally, as the use of probiotics becomes more popular, research on the interactions between probiotic-microbiota and psychotropic medications is necessary.

Efficacy and safety of Vonoprazan-based treatment of Helicobacter pylori infection: a systematic review and network meta-analysis

ObjectiveThe aim of this study was to evaluate the effectiveness and safety of the nine most widely studied Vonoprazan (VPZ)-based treatment regimens along with traditional Proton pump inhibitor (PPI)-based treatment regimens in eradicating Helicobacter pylori (H. pylori) infection.DesignThrough searching PubMed, Embase, Cochrane Library, Web of Science, we exclusively included randomized controlled trials (RCTs) to investigate the efficacy of VPZ-based and PPI-based therapies for H. pylori infection. The included studies were evaluated for methodological quality using the Cochrane bias risk assessment tool, and the data analysis software was used to analyze the data accordingly.ResultsThe RCTs were collected from the earliest available date up to August 2023. Twenty-one RCTs were included, with a total sample size of 5481. The results of the network meta-analysis showed that the eradication rate of the VPZ-based quadruple 14-day (VPZ-Q14) treatment regimen in Intention-to-treat (ITT) analysis was the highest (SUCRA: 0.874); The eradication rate of the VPZ-based quadruple 10-day (VPZ-Q10) treatment plan in Per-protocol (PP) analysis was the highest (SUCRA: 0.849). All regimens were well tolerated without significant differences. According to the probability ranking of safety, high-dose VPZ-based dual 14-day therapy (H-VPZ-D14) ranked first in SUCRA, reaching 0.952. This indicates that H-VPZ-D14 treatment is the safest with a relatively low incidence of adverse effect. Therefore, VPZ-based therapies not only have a higher eradication rate, but also possess satisfactory safety.ConclusionCompared with traditional PPI-based therapies, VPZ-based therapies have shown superior eradication effects. Based on the Ranking Plot of the Network, the VPZ-Q14 or VPZ-Q10 treatment regimen for H. pylori has a higher eradication rate and acceptable differences compared to other treatment regimens. In addition, for regions with high antibiotic resistance rates, we recommend a 14-day quadruple therapy with bismuth based on VPZ.

Mosquitocidal efficacy and pharmacokinetics of single-dose ivermectin versus three-day dose regimen for malaria vector control compared with albendazole and no treatment: An open-label randomized controlled trial

ObjectivesWhen malaria vectors consume ivermectin in a blood meal, their survival probability decreases, potentially reducing malaria transmission during mass drug administrations. However, questions remain regarding the optimal dosing. This study aimed to compare the mosquitocidal effect and pharmacokinetics of two-dose regimens of ivermectin for malaria vector control. DesignWe conducted an open-label randomized control trial in Kenya, staggered in blocks with sequential intervention groups and parallel controls. Participants were randomly assigned (2:1:1:1) using computer random-sequence generation, unstratified, with one block of six pharmacokinetics-only participants (single-dose ivermectin) and six blocks of four participants (3:1 intervention vs control), to receive single-dose ivermectin (400 mcg/kg, n = 12), three daily doses (3-day regimen 300 mcg/kg, n = 6), albendazole (400 mg, n = 6), or no treatment (negative control, n = 6). Our primary outcome was Anopheles gambiae survival (time-to-event [days]) after blood feeding up to 10 days after drug administration. We also evaluated pharmacokinetics (peak plasma and capillary blood concentration, areas under the plasma and capillary blood concentration-time curve from time of last administration to time of last observation, time to reach peak plasma and capillary blood concentration, terminal elimination half-life) up to 7 days after treatment. ResultsA total of 36 healthy volunteers aged 21-32 years were recruited into the study and followed up to completion, with two participants not attending the visit on day 28. All drug regimens were well-tolerated. Both regimens showed significant mosquitocidal effect in the first 7 days. At 10 days after treatment, the single dose presented superior longevity of effect (adjusted hazard ratio = 3.91; 95% confidence interval = 1.93-7.93; P <0.001) compared with the triple dose (adjusted hazard ratio = 1.79; 95% confidence interval = 0.88-3.62; P = 0.0.11). Albendazole had, overall, no mosquitocidal effect. ConclusionsIt is unclear why a single dose led to increased bio-efficacy compared with a triple dose. We recommend trials investigating ivermectin mass drug administrations for malaria control to consider single-dose ivermectin. A single-dose regimen is also expected to present additional operational advantages compared with a 3-day regimen, leading to improved programmatic suitability.