Days Of Therapy Research Articles

Antimicrobial Use Rates by Patient Care Units using NHSN Antimicrobial Use Option in TN Reporting Facilities, 2015–2023

Background: Tracking antimicrobial use (AU) is a Core Element of Hospital Antimicrobial Stewardship Programs and important to help curb the public health threat of antimicrobial resistance. The National Healthcare Safety Network’s (NHSN) AU Option serves as a way for facilities, healthcare systems, and health departments to track and report AU rates within their jurisdictions. Many analyses at the state and national levels do not assess unit-level AU rates. This study investigates AU rates among patient care units in Tennessee reporting facilities from 2015 to 2023 and the most frequently used antimicrobial agents based on AU rates within select unit types. Methods: A retrospective analysis was conducted utilizing data obtained from the NHSN AU Option for inpatient units in Tennessee acute care hospitals. Units were defined as critical care (including neonatal), ward, oncology ward, stepdown, operating room (OR), and mixed acuity and specialty care areas, termed ‘other’. Unit types with fewer than five facilities represented were excluded. AU rates were determined by Antimicrobial Days of Therapy (DOT) per 1000 Days Present (DP). Statistical analyses , including descriptive statistics and comparison among the units by ANOVA test , were calculated using SAS Version 9.4. Results: Eighty-three facilities reported at least one month of data into the NHSN AU Option between 2015–2023. Among 70 facilities reporting inpatient units, the highest AU rate was observed in oncology ward units (n=12, 1114.6 DOT/1000 DP). A significant difference in AU rates was observed between oncology ward units compared to different unit types (p < 0 .001). Vancomycin, ceftriaxone, and piperacillin/tazobactam were the most used antimicrobials with AU rates of 83, 76, and 65 DOT/1000 DP, respectively. Vancomycin AU rates were significantly higher in oncology ward units compared to stepdown, ward, other, and OR units (p < 0 .0001). Ceftriaxone AU rate was significantly higher in stepdown units compared to oncology ward, other, and OR units (p < 0 .0001). Piperacillin/tazobactam AU rate was significantly higher in critical care units compared to different unit types (p < 0 .0001). Conclusion: During the study period, the AU rate varied across hospital inpatient units in Tennessee, with the highest AU rate in oncology wards. This unit-specific approach is critical to address the diverse antimicrobial prescribing behaviors observed, indicating that interventions should be customized to each unit’s distinct antimicrobial usage patterns for successful stewardship efforts. Targeted strategies focused on individual wards rather than facility-wide initiatives appear essential for effective reduction in antibiotic usage.

Real-World Situation of Eradication Regimens and Risk Factors for Helicobacter pylori Treatment in China: A Retrospective Single-Center Study.

The success rate of Helicobacter pylori (H. pylori) eradication in China is declining. The aim of this study was to evaluate eradication outcomes in clinical practice and identifies factors contributing to treatment failure. A retrospective review was conducted on patients treated for H. pylori infection with 14-day bismuth-containing quadruple therapy at a Beijing medical center from January 2020 to December 2023. We analyzed demographic and clinical data, eradication rates across regimens, and performed multivariate analysis to pinpoint predictors of failure. Out of 3340 participants, 2273 (68.1%) achieved eradication. Amoxicillin-based combinations (69.2%) outperformed other antibiotic regimens (58.9%, p < 0.001), with amoxicillin plus doxycycline reaching a 71.4% success rate. Esomeprazole-based regimens were more effective (73.6%) than other PPI regimens (65.2%, p = 0.001), notably, a rabeprazole, amoxicillin, doxycycline, and bismuth combination had an 80.0% success rate. Age, gender, and smoking and drinking were significant eradication failure predictors. In real-world settings, 14-day amoxicillin and esomeprazole-based quadruple regimens have been demonstrated to be more effective than other regimens. Age, gender, and lifestyle habits are identified as independent risk factors for eradication failure. This study was registered in the Chinese Clinical Trial Registry on 08/01/2024 (clinical trial registration number: ChiCTR2400079647).

A multicenter, phase 1, Adult Brain Tumor Consortium trial of oral terameprocol for patients with recurrent high-grade glioma (GATOR)

Recurrent high-grade gliomas (rHGGs) have a dismal prognosis, where the maximum tolerated dose (MTD) of IV terameprocol (5days/month), a transcriptional inhibitor of specificity protein 1 (Sp1)-regulated proteins, is 1,700mg/day with median area under the plasma concentration-time curve (AUC) of 31.3μg∗h/mL. Given potentially increased efficacy with sustained systemic exposure and challenging logistics of daily IV therapy, here we investigate oral terameprocol for rHGGs in a multicenter, phase 1 trial (GATOR). Using a 3+ 3 dose-escalation design, we enroll 20 patients, with median age 60 years (range 31-80), 70% male, and median one relapse (range 1-3). Fasting patients tolerate 1,200mg/day (n= 3), 2,400mg/day (n= 6), 3,600mg/day (n= 3), and 6,000mg/day (n= 2) oral doses without major toxicities. However, increased dosage does not lead to increased systemic exposure, including in fed state (6,000mg/day, n= 4), with maximal AUC <5μg∗h/mL. These findings warrant trials investigating approaches that provide sustained systemic levels of transcription inhibitors to exploit their therapeutic potential. This study was registered at ClinicalTrials.gov (NCT02575794).

Fixed dose combination of aspirin and pantoprazole: Results of a multicenter, comparative, randomized, double-blind, double dummy, phase III study in Indian patients

ObjectiveTo compare the efficacy and safety of a fixed-dose combination of aspirin and pantoprazole with that of aspirin alone for the prevention of gastro duodenal mucosal damage in patients taking aspirin for secondary prevention of cardiovascular disease or cerebrovascular disease. MethodsThis was a comparative, double-blind, double-dummy, randomized, multicenter, phase III study conducted in patients taking aspirin ≤150 mg daily for ≥3 to ≤6 months and expected to require daily aspirin therapy for at least 6 months for the secondary prevention of cardiovascular disease or cerebrovascular disease. ResultsA total of 240 patients were randomized to receive either a fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg or aspirin 150 mg alone in a 2:1 ratio. The proportion of non-responders (patients experiencing gastroduodenal events) was 9.7 % in the test group (fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg) compared to 19.7 % in the comparator group (aspirin 150 mg) at week 12, while the proportions were 11.0 % in the test group and 22.4 % in the comparator group at the end of 24 weeks of treatment (p-value was <0.05 at week 12 and 24). GI injuries were significantly less in test group as compared to comparator group. Both drugs were well tolerated by all patients. ConclusionThe fixed-dose combination of aspirin 150 mg and pantoprazole 20 mg was found to be more efficacious and safer compared to aspirin 150 mg alone for the prevention of gastroduodenal mucosal damage in patients receiving aspirin.

High-frequency repetitive transcranial magnetic stimulation ameliorates memory impairment by inhibiting neuroinflammation in the chronic cerebral hypoperfusion mice.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF-rTMS remain unknown in chronic cerebral hypoperfusion (CCH). To investigate the effects of HF-rTMS on cognitive improvement and its potential mechanisms in CCH mice. Daily HF-rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF-rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP-2, synapsis, Myelin basic protein(MBP), and brain-derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase-3, Bax, and Bcl-2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL-1β, IL-6, and Tumor Necrosis Factor(TNF)-α were detected by qPCR in the hippocampus of mice in each group. Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF-rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP-2, synapsis, MBP, and BDNF, while HF-rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF-rTMS treatment suppressed these changes. HF-rTMS decreased BCAS-induced neuronal apoptosis and the expression of pro-apoptotic protein (Caspase-3 and Bax) and increased the expression of anti-apoptotic protein (Bcl-2). In addition, HF-rTMS inhibited the expression of inflammatory cytokines (IL-1β, IL-6, and TNF-α). HF-rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.

Emerging Therapeutics Targeting Cellular Stress Pathways to Mitigate End-Organ Damage in Type 1 Diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by insulin deficiency and impaired glucose regulation. While daily insulin therapy is life-saving, many patients struggle to achieve optimal glycemic control, leading to microvascular complications affecting various organs, including the kidneys and the liver. This review aims to summarize the current state of knowledge regarding the pathogenesis of hepatic and renal complications in T1D, highlight recent advances in potential therapeutic targets, and provide evidence-based recommendations for mitigating end-organ damage. Chronic hyperglycemia drives diabetic complications through several interrelated mechanisms, including increased polyol pathway flux, advanced glycation end-product (AGE) formation, protein kinase C activation, and mitochondrial reactive oxygen species overproduction. In the liver, these processes contribute to non-alcoholic fatty liver disease, with up to 50% of T1D patients developing hepatic steatosis. Diabetic nephropathy, affecting 25%–40% of long-term T1D patients, is characterized by glomerular basement membrane thickening, mesangial expansion, and tubulointerstitial fibrosis. Recent innovations in T1D management include genomics and precision medicine approaches, gut microbiome modulation, nanomedicine, and artificial intelligence-driven glucose monitoring systems. Emerging immunotherapies aim to fundamentally modify the autoimmune response in T1D. Mitigating T1D complications requires intensive glycemic control, targeted pharmacotherapy, and lifestyle modifications. Emerging therapies and precision medicine approaches offer promising avenues. Ongoing research into molecular mechanisms remains crucial for developing novel interventions and improving long-term outcomes in T1D patients.

Using Real-World Research to Study the Impact of Chronic Daily Therapy Discontinuation in Cystic Fibrosis: The Home-Reported Outcomes in Cystic Fibrosis 2 Study Design

Using Real-World Research to Study the Impact of Chronic Daily Therapy Discontinuation in Cystic Fibrosis: The Home-Reported Outcomes in Cystic Fibrosis 2 Study Design

Blood serum biomarkers in the dynamics of treatment for cerebrovascular pathology in post-COVID-19 patients

Neurological manifestations after COVID-19 infections can be attributed to chronic immune and inflammatory reactions induced by SARS-CoV-2, as well as endothelial dysfunction and other vascular issues. This study included 24 patients with cerebrovascular disease (CVD) who had contracted COVID-19 1 &amp;ndash; 1.5 years before the examination (experimental group) and 20 patients with CVD who had not previously been infected with the coronavirus (comparison group). Both groups were representative in terms of age and gender. Blood serum biomarkers, including interleukin (IL)-6, endothelin-1 (ET-1), and vascular endothelial growth factor A (VEGF-A), were tested before and after a 14-day standard complex therapy in the hospital at our institute using appropriate enzyme-linked immunosorbent assay reagent kits. Increases in the levels of IL-6 (by 20%), ET-1 (by 200%), and VEGF-A (by 100%) were observed in patients with CVD who had contracted COVID-19 1 &amp;ndash; 1.5 years earlier compared to the comparison group. The effectiveness of a 2-week therapeutic intervention in patients with a history of COVID-19 was found only for VEGF-A: its serum level decreased twofold, leading to the normalization of this indicator. The concentrations of IL-6 and ET-1 were not affected by the treatment. In addition, the serum levels of ET-1 and VEGF-A in unvaccinated individuals exceeded those in vaccinated patients.

Structure-activity relationship of pharmacophores and toxicophores: the need for clinical strategy.

Sometimes clinical efficacy and potential risk of therapeutic and toxic agents are difficult to predict over a long period of time. Hence there is need for literature search with a view to assessing cause of toxicity and less efficacy of drugs used in clinical practice. Hence literatures were searched for physicochemical properties, chemical formulas, molecular masses, pH values, ionization, receptor type, agonist and antagonist, therapeutic, toxic and structure-activity relationship of chemical compounds with pharmacophore and toxicophore, with a view to identifying high efficacious and relative low toxic agents. Inclusion criteria were manuscripts published on PubMed, Scopus, Web of Science, PubMed Central, Google Scholar among others, between 1960 and 2023. Keywords such as pharmacophore, toxicophore, structure-activity-relationship and disease where also searched. The exclusion criteria were the chemicals that lack pharmacophore, toxicophore and manuscripts published before 1960. Findings have shown that pharmacophore and toxicophore functional groups determine clinical efficacy and safety of therapeutics, but if they overlap therapeutic and toxicity effects go concurrently. Hence the functional groups, dose, co-administration and concentration of drugs at receptor, drug-receptor binding and duration of receptor binding are the determining factors of pharmacophore and toxicophore activity. Molecular mass, chemical configuration, pH value, receptor affinity and binding capacity, multiple pharmacophores, hydrophilic/lipophilic nature of the chemical contribute greatly to functionality of pharmacophore and toxicophore. Daily single therapy, avoidance of reversible pharmacology, drugs with covalent adduct, maintenance of therapeutic dose, and the use of multiple pharmacophores for terminal diseases will minimize toxicity and improve efficacy.

A Longitudinal Study of Adherence among Cystic Fibrosis Patients: Associations with Gratitude Over the Course of One Year.

Daily airway clearance therapy (ACT) is a critical aspect of treatment in cystic fibrosis (CF), but poor adherence is a prominent concern. Identifying factors that might enhance or diminish adherence is a priority for treatment centers. Gratitude, a generalized tendency to notice and appreciate positive facets of experience, is a psychosocial resource that has commanded growing research interest. This longitudinal study examined whether gratitude at baseline was associated with ongoing or persistent ACT adherence over the course of a year. Trait gratitude was evaluated at baseline using a validated measure, among adults receiving care at a regional CF treatment center. Self-reported adherence to ACT was assessed at baseline, 6months, and 12months using the Cystic Fibrosis Treatment Questionnaire. Average age of participants was 27.2years, 45.5% were women, and 19.7% had severe disease. In multivariable logistic regression models that accounted for disease severity (Forced Expiratory Volume1% predicted) and other clinical and demographic variables, individuals with higher baseline gratitude were significantly more likely to demonstrate persistent adherence over the course of the year. Gratitude remained predictive after additionally adjusting for other well-known psychosocial resource variables (social support and emotional well-being). This is among the first demonstrations that gratitude is associated with persistent self-reported adherence to treatment over time. Findings suggest that gratitude may be important psychosocial resource for adults with CF, as they contend with complex, highly burdensome treatment regimens. Further research is warranted to examine these relationships and their impact on downstream health outcomes.

Frequency of Delayed Puberty in Boys with Contemporary Management of Duchenne Muscular Dystrophy.

Delayed puberty is thought to be common in boys with Duchenne muscular dystrophy (DMD) treated with long term oral glucocorticoid. This study aims to report the frequency of delayed puberty in DMD from examination by a paediatric endocrinologist alongside detailed endocrine investigations. All boys with DMD aged at least 14 years in January 2022 known to the paediatric neuromuscular service (2016-2022) were included in this study. Delayed puberty was defined based on testicular volume and genital staging in comparison to published puberty nomogram. Twenty-four out of 37 boys (65%) had evidence of delayed puberty, 23/24 (96%) of those with delayed puberty were on glucocorticoid therapy all of whom were on daily glucocorticoid. On the other hand, 7/13 (54%) of those with normal timing of puberty were on glucocorticoid; 2/7 (29%) were on the intermittent regimen. Of those who were on daily glucocorticoid therapy at the time of assessment of puberty, 23/28 (82%) had evidence of delayed puberty. In boys with delayed puberty, endocrine investigations showed low luteinizing hormone (LH) with undetectable testosterone levels, a pre-pubertal response with lutenizing hormone releasing hormone test and sub-optimal testosterone levels with prolonged human chorionic gonadotropin stimulation. The frequency of delayed puberty in boys with DMD was 65%. Eighty-two percent of adolescent boys with DMD on daily glucocorticoid had evidence of delayed puberty. Biochemical investigations point to functional central hypogonadism in these adolescents. Our data supports the routine monitoring of puberty in boys with DMD.

Evaluation of antimicrobial stewardship activities using antibiotic spectrum coverage

Recently, the days of antibiotic spectrum coverage (DASC) using the antibiotic spectrum coverage (ASC) score was reported as a new tool for measuring antimicrobial use. The days of therapy (DOT) are required to calculate the DASC, making it impossible to use when patient-level information is unavailable. Therefore, we have defined a new measure of antimicrobial use for antimicrobial spectrum coverage (AUSC) using antimicrobial use density (AUD) and ASC scores. In this study, we have investigated the use of antimicrobial agents retrospectively examined for monthly prescriptions between 2016 and 2022, and whether the AUSC could be used as a new measure. Our data showed that the AUD, AUSC, DOT, and DASC increased, whereas AUSC/AUD and DASC/DOT decreased over the study period. In addition, no correlation was found between DOT and DASC/DOT (ρ = − 0.093, p = 0.399), whereas there was a weak correlation between AUD and AUSC/AUD (ρ = − 0.295, p = 0.006). Therefore, in this study, the use of AUSC is considered less beneficial when DASC can be calculated based on DOT. On the other hand, in institutional settings where DOT cannot be calculated, AUSC may be useful as a new measure to evaluate antimicrobial use.

Automated surveillance of antimicrobial consumption in intensive care, northern Sweden: an observational case study

BackgroundThe digitalization of information systems allows automatic measurement of antimicrobial consumption (AMC), helping address antibiotic resistance from inappropriate drug use without compromising patient safety.ObjectivesDescribe and characterize a new automated AMC surveillance service for intensive care units (ICUs), with data stratified by referral clinic and linked with individual patient risk factors, disease severity, and mortality.MethodsAn automated service collecting data from the electronic medical record was developed, implemented, and validated in a healthcare region in northern Sweden. We performed an observational study from January 1, 2018, to December 31, 2021, encompassing general ICU care for all ≥18-years-olds in a catchment population of 270000 in secondary care and 900000 in tertiary care. We used descriptive analyses to associate ICU population characteristics with AMC outcomes over time, including days of therapy (DOT), length of therapy, defined daily doses, and mortality.ResultsThere were 5608 admissions among 5190 patients with a median age of 65 (IQR 48-75) years, 41.2% females. The 30-day mortality was 18.3%. Total AMC was 1177 DOTs in secondary and 1261 DOTs per 1000 patient days and tertiary care. AMC varied significantly among referral clinics, with the highest total among 810 general surgery admissions in tertiary care at 1486 DOTs per 1000 patient days. Case-mix effects on the AMC were apparent during COVID-19 waves highlighting the need to account for case-mix. Patients exposed to more than three antimicrobial drug classes (N = 242) had a 30-day mortality rate of 40.6%, with significant variability in their expected rates based on admission scores.ConclusionWe introduce a new service and instructions for automating local ICU-AMC data collection. The versatile long-term ICU-AMC metrics presented, covering patient factors, referral clinics and mortality outcomes, are expected to be beneficial in refining antimicrobial drug use.

Effectiveness of Jena DM® Herbal Formulation as Complementary Therapy to Conventional Oral Hypoglycemic Agents in Type-2 Diabetes Mellitus: A Quasi-experimental Study.

There is vast preclinical evidence that indicates that extracts from several Artemisia plant species have significant antidiabetic benefits. However, clinical evidence is limited to this effect. We sought to evaluate the effectiveness ofJena DM® (anArtemisia annua-based poly-herbal formulation) on glycemic control (Hb A1C) and insulin metabolism (HOMA), when administered as a complementary therapy in type-2 diabetes mellitus (T2DM). This study was supported by a research grant (JRD005) from Jena Herbals (U) Ltd, which is a local herbal medicines manufacturing facility in Uganda. We conducted a 12-week quasi-experimental study, involving 118 patients under routine follow-up at a diabetes and endocrinology clinic. Random assignment to either conventional or experimental study groups was done using a random number generator (Microsoft Excel version 16.0). Participant sociodemographic and clinical data as well as whole blood samples (3-5 mL) were obtained at scheduled clinic visits. Medication adherence was assessed using the Hill-Bone Scale, and adverse drug events (ADEs) using the Naranjo causality and the National Institute of Allergy and Infectious Diseases, Division of AIDS (DAIDS) scales. Group differences in glycemic control (HbA1C), fasting serum insulin (FSI) indices (% HOMA2-B, HOMA-IR), and other cardiometabolic parameters were assessed using independent samples t-test, and Pearson chi-square statistical tests were used. A p-value <0.05 was considered statistically significant. Ethical approvals were obtained before the study commencement. 12-week daily complementary therapy withJena DM® showed no significant effect on Hb A1C reduction (0.1 (95% CI: -0.56, 0.80) %;p=0.798); however, we observed a significant reduction in total body weight (2.0 (95% CI: 0.73, 3.28) kg;p=0.002). The overall frequency of self-reported ADEs including dizziness was significantly higher among patients that usedJena DM® (p=0.001).Epigastric pain was the most severe ADE necessitating clinical management. There was no significant difference in the homeostatic model assessment for insulin resistance (HOMA2-IR) between study groups. In contrast to a few studies that previously showed significanthypoglycemic effects ofArtemisia-basedextracts, this study did not show a statistically significant reduction on HbA1C during a 12-week complementary use ofJena DM® in patients withT2DM. Based on the findings of this study, future research should evaluate the long-term effects ofJena DM® on body weight, overall insulin metabolism, and the subsequent effect on glycemic control in T2DM.

Impact of an antimicrobial stewardship programme on antibiotic utilization and resistance burden in patients with acute leukaemia: an 11-year longitudinal cohort study using interrupted time-series analysis.

Antimicrobial resistance (AMR), driven by inappropriate and overuse of antibiotics, poses a significant threat, especially to patients with acute leukaemia. To evaluate the impact of antimicrobial stewardship programmes (ASPs) on antibiotic use and analyse temporal changes in bloodstream infections (BSI) caused by AMR organisms. We performed a retrospective, interventional, longitudinal cohort study spanning an 11-year period. ASPs included optimizing antibiotic use, enhancing tracking and reporting systems and delineating leadership and accountability. A segmented regression model of interrupted time series was used to evaluate the trend of antibiotic consumption and BSI with AMR organisms after the interventions. A total of 3296 BSI episodes with 454 419 days of therapy (DOT) from 7754 patients were obtained. ASPs were significantly associated with an immediate reduction [-70.03 DOT/1000 patient-days (PD), P = 0.036] and a decreasing trend (-11.65 DOT/1000 PD per quarter, P < 0.001) in overall antibiotic use. The increasing incidence of BSI with AMR before ASP intervention was notably curbed and revealed a decreasing trend (slope change: -0.06 BSI/1000 PD per quarter, P = 0.002). The decreasing trend was more significant for Enterobacterales: ciprofloxacin-resistant and ESBL-producing isolates showed a slope change of -0.06 BSI/1000 PD and -0.08 BSI/1000 PD per quarter, respectively (all P < 0.05). However, Pseudomonas aeruginosa BSI increased. Multidimensional ASPs effectively reduced both the immediate and trends in overall antibiotic usage even in patients with acute leukaemia. Additionally, there was a notable decrease in the incidence of BSI caused by AMR organisms, particularly among Enterobacterales.

Comprehensive Analysis of Factors Associated With Helicobacter pylori Eradication Therapy

Objectives: Associated factors for the failure of &lt;i&gt;Helicobacter pylori&lt;/i&gt; (HP) eradication have been evaluated in many studies; however, the different study population of previous studies prevents us from understanding the comparative risk between factors. We aimed to comprehensively investigate factors associated with successful HP eradication based on a single study population.Methods: We retrospectively reviewed the medical records of adults diagnosed with HP infection between March 2021 and October 2022 at Hanyang University Guri Hospital. The study categorized eradication treatment methods based on the type of acid blockers (proton pump inhibitor [PPI] or potassium-competitive acid blocker [P-CAB]), antibiotic combination, and treatment duration. Demographics and clarithromycin-resistance mutation status were also considered as potential factors of HP eradication.Results: A total of 554 patients who received first-line HP eradication therapy were included. In the full-analysis set, the eradication rates according to the regimen were as follows: 7-day tegoprazan-based triple, 61.6%; 14-day tegoprazan-based triple, 77.5%; 14-day rabeprazole-based triple, 71.1%; 10-day rabeprazole-based concomitant, 73.1%; 10-day tegoprazan-based concomitant, 80.5%. The 14-day triple and 10-day concomitant therapies showed a superior eradication rate to the 7-day triple therapy regardless of the type of acid blockers (PPI or P-CAB). Additionally, clarithromycin-resistance mutation was the strongest predictor for eradication failure (hazard ratio 9.86 [95% confidence interval, 2.07–46.97]).Conclusions: The 14-day triple and 10-day concomitant therapy was superior to the 7-day triple therapy regardless of PPI or P-CAB use. However, clarithromycin-resistance mutation status was a more powerful predictor for HP eradication than the type of antibiotics and treatment duration.

Experience of rigorous practice of antimicrobial stewardship program and its impact on antibiotic consumption

Objectives: Antimicrobial resistance (AMR) is the next pandemic with a huge global economic burden. A customized antimicrobial stewardship program (AMSP) is a well-recognized tool for containment of AMR. The current study was undertaken to identify the impact of AMSP measures on the trends of antibiotic consumption rates, e.g., defined daily dose (DDD) and days of therapy (DOT) per 100 patient days in pre-identified areas of the hospital. Materials and Methods: The present study was a case-record-based extended cross-sectional study carried out in a tertiary care institute in central India from January 2021 to September 2021. Time-bound feasible sampling was undertaken, and all cases were included without any exclusion criteria. The study was approved by the Ethics Committee of the Institute and funded by the Indian Council of Medical Research (ICMR). Statistical Analysis: The data was entered into a spreadsheet. The calculation of DDD and DOT was performed individually for each antibiotic as per WHO tool per 100 patient days. Results: In high-priority areas such as intensive care unit and high dependency unit, the top three DDD/100 days were meropenem (77.9), colistin (41.4), and piperacillin-tazobactam (13.5) versus the top 3 DOT/100 patient days were meropenem (40.5), colistin (20.9), and piperacillin-tazobactam (15.7). In low-priority areas such as general wards, the top 3 DDD/100 patient days were meropenem (45.4), piperacillin-tazobactam (22.6), and cefoperazone (5.0) versus the top three DOT/100 patient days were meropenem (45.4), cefoperazone (44.9), and piperacillintazobactam (22.6). There was a downward trend of consumption of almost all these antibiotics when measured at baseline and the next two quarters. DDD and DOT per 100 patient days had a positive linear correlation during the study period. Conclusions: The present study demonstrates about 50% reduction in consumption of ICMR priority antibiotics with a yearlong AMSP. DDD and DOT per 100 patient days can be calculated with minimal effort, even in extremely busy hospitals. DOT tools are less labor-intensive and, hence, should be the pivotal tool for antibiotic exposure measurement.

Daily compared with alternate-day levamisole in pediatric nephrotic syndrome: an open-label randomized controlled study.

Levamisole is less expensive and has a better toxicity profile compared to other steroid sparing agents used in nephrotic syndrome. It has a plasma half-life of 2.0 to 5.6hours, but is conventionally administered on alternate days. We aimed to assess whether daily levamisole is safe and more effective than standard alternate-day therapy in maintaining remission in children with frequently relapsing or steroid-dependent nephrotic syndrome (FR/SDNS). An open-label randomized controlled trial was conducted in children with FR/SDNS. Group A received daily while Group B received alternate-day levamisole (2-3mg/kg/dose) for 12months. Prednisolone was tapered off by 3months. Patients were monitored for relapses, further steroid requirement, and adverse effects. A total of 190 children with FR/SDNS (94 in Group A and 96 in Group B) were analyzed. Sustained remission for 12months was observed in 36% of Group A and 27% of Group B patients (p = 0.18). Numbers completing 12months in the study were 67% in Group A and 56% in Group B (p = 0.13). Time to first relapse, persistent FR/SDNS, and withdrawal due to poor compliance were statistically similar in both groups, while relapse rate and cumulative steroid dosage were significantly lower in Group A compared to Group B (p = 0.03 and p = 0.02, respectively). The incidence of adverse effects was comparable in both groups, with reversible leucopenia and hepatic transaminitis being the commonest. Daily levamisole therapy was not superior to alternate-day therapy in maintaining sustained remission over 12months. Nevertheless, relapse rate and cumulative steroid dosage were significantly lower without increased adverse effects.

Recovery of optimal vitamin D improves responsiveness to phosphodiesterase-5 inhibitors therapy in pulmonary arterial hypertension

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): R.A. has received funding from the European Union’s Horizon 2020 research and innovation programme under Marie-Curie grant agreement Nº 847635. Introduction Vitamin D (vitD) deficiency is highly prevalent in patients with pulmonary arterial hypertension (PAH). Moreover, PAH-patients with lower levels of vitD have worse prognosis. We demonstrated that in animals with PAH and severe deficit of vitD, restoring vitD levels to an optimal range partially improves some pathophysiological features of PAH. Also, recent evidence suggests that vitD deficiency may cause insufficient response to phosphodiesterase-5 inhibitors (PDE5i), such as sildenafil, in some patients with PAH. Thus, in this study, we hypothesize that the recovery of optimal vitD levels in experimental PAH might help to improve responsiveness to PDE5i therapy. Methods Male Wistar rats were fed a vitD-free diet for five weeks and then received a single dose of Su5416 (20 mg/Kg) and were exposed to vitD-free diet and chronic hypoxia (10% O2) for three weeks to induce PAH. Following this, vitD deficient rats with PAH were housed in room air and divided into two groups: (a) daily tadalafil therapy (oral;10mg/kg) + continued vitD-free diet (n=9) or (b) daily tadalafil therapy (oral;10mg/kg) + single oral dose of 50,000 IU/Kg of vitD plus standard diet (n=9) for four weeks. Animals were then used for exercise capacity evaluation, invasive haemodynamic, pulmonary vascular analysis, and sample collection. Evolution of cardiac (dys)function was assessed by echocardiography. Results Recovering optimal vitD levels improved pulmonary endothelial function, measured by an increase in the endothelium-dependent vasodilator response to acetylcholine. It also increased the vasodilator response to sildenafil. Moreover, pulmonary small artery (&amp;lt;55 µm) remodeling was decreased in vitD-restored group, as measured by a decline in mean lumen/total ratio and mean medial thickness. In a morphometric analysis, vitD treatment attenuated increases in both right ventricle (RV) and right atrial hypertrophy, as well as the fulton index. VitD supplementation also improved the exercise capacity with increases seen in distance run, evaluated by endurance tests in a treadmill set. RV catheterization showed that vitD did not decreased the RV dysfunction, evaluated by end-systolic and end-diastolic pressure. Similar to the RV, no alterations were observed in pulmonary artery pressures. However, echocardiographic analysis revealed an improved pulmonary flow in the vitD-restored group, where pulmonary artery acceleration time normalized to ejection time ratio and pulmonary artery velocity-time integral were increased. It also improved tricuspid annular plane systolic excursion (TAPSE). Conclusion Altogether, these data suggest that in animals with PAH treated with tadalafil, restoring vitD levels to an optimal range improves some pathophysiological features of PAH. Therefore, in addition to recovery of optimal vitD status being indicated to restore calcium homeostasis in those PAH patients with severe deficiency, it might help to improve responsiveness to PDE5i.

S2k guideline for the treatment of hidradenitis suppurativa / acne inversa - Short version.

The S2k guideline on hidradenitis suppurativa/acne inversa (HS/AI) aims to provide an accepted decision aid for the selection/implementation of appropriate/sufficient therapy. HS/AI is a chronic recurrent, inflammatory, potentially mutilating skin disease of the terminal hair follicle-glandular apparatus, with painful, inflammatory lesions in the apocrine gland-rich regions of the body. Its point prevalence in Germany is 0.3%, it is diagnosed with a delay of 10.0 ±9.6 years. Abnormal differentiation of the keratinocytes of the hair follicle-gland apparatus and accompanying inflammation form the central pathogenetic basis. Primary HS/AI lesions are inflammatory nodules, abscesses and draining tunnels. Recurrences in the last 6 months with at least 2 lesions at the predilection sites point to HS/AI with a 97% accuracy. HS/AI patients suffer from a significant reduction in quality of life. For correct treatment decisions, classification and activity assessment should be done with a validated tool, such as the International Hidradenitis Suppurativa Severity Scoring System (IHS4). HS/AI is classified into two forms according to the degree of detectable inflammation: active, inflammatory (mild, moderate, and severe according to IHS4) and predominantly inactive, non-inflammatory (Hurley grade I, II and III) HS/AI. Oral tetracyclines or 5-day intravenous therapy with clindamycin are equal to the effectiveness of clindamycin/rifampicin. Subcutaneously administered adalimumab, secukinumab and bimekizumab are approved for the therapy of HS/AI. Various surgical procedures are available for the predominantly non-inflammatory disease form. Drug/surgical combinations are considered a holistic therapy method.