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Rapid Response Antimicrobial Peptide Design Strategy Driven by Meta-Learning for Emerging Drug-Resistant Pathogens.
Authors: Yu Y et al
Abstract
Antimicrobial resistance (AMR) presents a critical global health threat requiring urgent intervention. In order to swiftly respond to and control the spread of emerging drug-resistant bacteria at the onset of their proliferation, our aim is to develop a Rapid Response Antimicrobial Peptide (AMP) design strategy (RR-ADS). This framework addresses the challenge of limited pathogen-specific data by achieving robust generalization from minimal samples by meta-learning and reinforcement learning, optimizing both biocompatibility and efficacy against drug-resistant pathogens. The model has achieved satisfactory results across multiple evaluation metrics, demonstrating the capability to accurately identify and generate AMPs targeted against drug-resistant bacteria with minimal sample sizes. Within 2 weeks, AMPs against multidrug-resistant Acinetobacter baumannii were successfully designed and experimentally verified , achieving a 93.3% positive rate. RR-ADS has effectively demonstrated the potential of meta-learning in tasks involving bioactive peptides and holds promise as an effective alternative measure to address infectious disease public health emergencies.
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Lower urinary tract infection in women: diagnosis, management and prevention.
Authors: Dwyer L et al
Abstract
Urinary tract infection (UTI) is a common condition in women, causing symptoms that can have a detrimental effect on their everyday life and, for some, can result in hospitalisation, sepsis and death. The treatment of UTIs accounts for a significant proportion of antibiotic prescribing, which contributes to the growing issue of antimicrobial resistance. To try to address both of these issues, strategies for UTI prevention, accurate diagnosis and appropriate treatment have become national priorities in the UK. This article discusses current evidence-based guidelines on the diagnosis, management and prevention of lower UTI in women with the aim of enhancing nurses’ awareness of these guidelines and to inform their practice. Nurses should be mindful that this issue may also affect trans men and non-binary people.
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The first report of antibiotic resistance and virulence factor profiles in multidrug-resistant clinical isolates of Klebsiella pneumoniae from Pontianak, Indonesia.
Authors: Mardhia M et al
Abstract
Objectives: Klebsiella pneumoniae is known as one of the most common causes of hospital-acquired infections. Its prevalence poses substantial challenges to both hospital and public health systems, particularly due to the rise of multidrug-resistant strains. Understanding the epidemiology and resistance properties of K. pneumoniae can inform antimicrobial stewardship and infection control programs. A cross-sectional study was employed from November 2021 to November 2023.
Methods: A total of 24 isolates underwent antimicrobial susceptibility testing using the disk diffusion method, an extended-spectrum beta-lactamase (ESBL) production test, and molecular gene detection.
Results: The study found that 95.8% of clinical isolates were classified as multidrug-resistant. All isolates were resistant to ampicillin (100%). A high percentage of isolates were resistant to cefazolin (91.7%), ceftriaxone (87.5%), cefotaxime (87.5%), cefepime (87.5%), ciprofloxacin (83.3%), and sulfamethoxazole-trimethoprim (83.3%). Of the 24 isolates, 87.5% harbored ESBL genes, while the frequencies for GES, NDM, SIM, and OXA-48 were 16.7%, 20.8%, 8.3%, and 41.7%, respectively. Notably, the OXA-23 and OXA-51 genes, which are typically associated with Acinetobacter baumannii, were detected in 16.7% and 20.8% of isolates, respectively. Moreover, the prevalence of virulence genes rmpA, acrAB, and tolC was 0%, 95.8%, and 87.5%, respectively.
Conclusion: This study demonstrated a high level of antibiotic resistance and a significant presence of virulence genes among K. pneumoniae isolates. Consequently, these findings represent a critical public health issue that requires heightened awareness among all stakeholders, including health workers.
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Hand hygiene versus additional non-sterile gloves and gowns use to prevent sepsis in preterm infants colonized with multi-resistant drug bacteria: the study protocol of the cluster-randomized, cross-over, non-inferiority BALTIC trial.
Authors: Faust K et al
Abstract
Background: Infections are highly relevant for neonatal mortality and long-term morbidities in survivors. Therefore, it is an urgent need to optimize and evaluate infection prevention and control (IPC) strategies. Several infection outbreaks in German neonatal intensive care units (NICUs) required rapid responses by hospitals and improved future preparedness. As a consequence, German authorities recommended weekly colonization screening on NICUs. This screening aims to detect multidrug-resistant organisms (MDRO) and bacteria with high transmissibility. According to these guidelines, infants colonized with multiresistant gram-negative (MRGN) bacteria with in-vitro resistance to piperacillin and cephalosporins (2MRGN) should be cared wearing non-sterile gloves and gowns in addition to standard hygiene precautions. Whether these extended IPC measures have an individual benefit for infants or contribute to the prevention of infection outbreaks has not yet been scientifically proven. This study aims to evaluate the effect of hand desinfection as compared to hand desinfection + gloves and gowns (barrier care) for the care of 2MRGN colonized infants in NICUs on infection and transmission rates through a multicenter, cluster randomized controlled trial (BALTIC study, Barrier protection to lower transmission and infection rates with Gram-negative 2-MRGN in preterm children).
Methods: 12 participating NICUs were randomly allocated to two trial arms: receiving the intervention “standard precautions with a special focus on hand desinfection” or control (standard precautions “plus” barrier care) for the care of 2MRGN positive infants. Cross over was performed after 12 months for another 12 months per site. Primary outcome was the rate of healthcare-associated (HA) Gram-negative bloodstream infections. Secondary outcomes included transmission rate with screening relevant bacteria, overall rate of clinical and culture-proven infections, number of antibiotic cycles and desinfectant use. Regular trainings and hygiene audits are standardized co-interventions.
Benchmarking results: According to our single center data, 9.3% of NICU-treated infants are colonized with 2MRGN during their hospital stay. BALTIC randomized the first center in October 2020 and finished data collection including close-out monitoring in January 2024. Data analysis will be completed in May 2025.
Conclusions: BALTIC should contribute to better evidence on the effectiveness of hand desinfection and extended barrier precautions in critically ill newborns. Further benefits include comprehensive multi-center data collection on MDRO colonization dynamics, an improved awareness on IPC strategies and establishment of network platforms including antimicrobial stewardship programs.
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Implementation of hospital antimicrobial stewardship programmes in low- and middle-income countries: a qualitative study from a multi-professional perspective in the Global-PPS network.
Authors: Pauwels I et al
Abstract
Background: Hospitals in low- and middle-income countries (LMIC) face context-specific challenges in implementing antimicrobial stewardship (AMS) programmes. The Global Point Prevalence Survey (Global-PPS) project has established a network of hospitals across 90 countries, using point prevalence surveys to monitor antimicrobial use and guide AMS activities. However, little is known about AMS implementation in these hospitals. Using qualitative research, we aim to explore the implementation process in LMIC hospitals within the Global-PPS network and the factors influencing it, identify potential implementation strategies, and evaluate the role of Global-PPS in this process.
Methods: A qualitative study was conducted using semi-structured online interviews with healthcare workers (HCWs) involved in AMS in LMIC hospitals within the Global-PPS network. Participants were selected using a combination of convenience and purposive sampling and included clinicians, microbiologists, pharmacists, and nurses. Interviews followed a topic guide based on the integrated checklist of determinants of practice (TICD Checklist). Transcripts were analysed using a combination of inductive and deductive thematic analyses.
Findings: Twenty-two HCWs from 16 countries were interviewed. Hospitals were in different stages of the AMS implementation process at the time of the study, from pre-implementation to institutionalisation of AMS as part of the continuous quality improvement process. While the Global-PPS provided a valuable tool for education and implementation, contextual barriers often hindered the translation of findings into targeted interventions. Four themes influenced AMS implementation, “institutional support and resource allocation”, “AMS team functioning, roles, and expertise”, “adoption and integration of AMS recommendations”, and “data-driven decision-making” as a cross-cutting theme. Key determinants included AMS team competencies, multidisciplinary teams, sustainable funding and leadership support, diagnostic capacity, and reliable data to inform interventions. Also the authors identified various strategies employed by local AMS teams to enhance implementation.
Conclusions: This study examines AMS implementation in LMIC hospitals in the Global-PPS network and identifies key determinants. AMS teams address challenges through task shifting, local engagement and ownership. While empirical evidence on the effectiveness of these strategies is limited, these insights can guide future AMS interventions and studies within LMIC hospitals. Strengthening AMS requires bridging the gap between measurement and action and expanding research on behaviour change.
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Dominance of antimicrobial resistance bacteria and risk factors of bacteriuria infection among pregnant women in East Africa: implications for public health
Authors: Molla Getie Mehari
Abstract
Background: Bacterial infections in pregnancy pose significant health risks in East Africa. This study estimates pooled prevalence and identifies key risk factors, addressing limited data to improve maternal health outcomes in the region.
Methods: This study employed a systematic review and meta-analysis, analyzing data from eight East African studies (2016-2021). Searches spanned PubMed, Embase, Scopus, and more, with manual reference checks. Data quality was assessed via the Newcastle-Ottawa Scale. RevMan software with a random-effects model estimated pooled prevalence and hazard ratios for risk factors.
Results: A pooled analysis of antimicrobial resistance (AMR) bacterial isolates from pregnant women in East Africa highlights concerning prevalence rates of various pathogens. Escherichia coli emerged as the most common pathogen, present in 43% (95% CI: 37-48%) of cases, followed by Staphylococcus aureus at 20% (95% CI: 0.12, 0.29) and Corynebacterium, Enterococcus, and Nocardia species (CONs) in 16% (95% CI: 10-23%) and 16% (95% CI: 12-21%) (Prevalence of K. pneumoniae). A very small proportion 6% (95% CI: 2 – 11%) was found to be infected with Pseudomonas aeruginosa. The forest plot highlights risk factors for infections in pregnant women in East Africa: antibiotic use (HR: 2.0, 95% CI: 1.5-2.6), smoking (HR: 1.3, 95% CI: 1.0-1.6), poor sanitation (HR: 1.8, 95% CI: 1.2-2.4), diabetes (HR: 2.1, 95% CI: 1.5-2.8), and age > 30 years (HR: 1.5, 95% CI: 1.1-2.0).
Conclusions: This analysis reveals a significant prevalence of bacterial infections, particularly Escherichia coli, among pregnant women in East Africa, with antimicrobial resistance (AMR) complicating treatment. The study identified several key risk factors, including antibiotic use, smoking, poor sanitation, diabetes, and age over 30, which are associated with higher rates of infection. While these findings emphasize the need for further research, the results suggest that routine bacterial screening, AMR surveillance, improved sanitation, and antibiotic stewardship are important steps in mitigating the impact of these infections. Public health strategies should prioritize high-risk groups, encourage hygiene practices, and continue to guide policy and interventions through ongoing studies.
Keywords: Escherichia coli; Antimicrobial Resistance (AMR); Bacterial infections; Pregnant women; Public Health interventions.
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Impact of all-oral bedaquiline-based shorter regimens in the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis
Authors: Ginenus Fekadu
Abstract
Background: Drug-resistant tuberculosis (DR-TB) presents a significant global obstacle to TB control efforts, necessitating improved intervention strategies. The introduction of potent drugs, such as bedaquiline (Bdq), has led to the development of shorter treatment regimens. This systematic review and meta-analysis aimed to examine the impact of these regimens, synthesising data from recent clinical trials and observational studies.
Methods: We searched multiple databases, including Medline and Scopus, for studies published from 2012 to February 2024. Eligible studies included clinical trials and cohort studies involving adults diagnosed with DR-TB treated with Bdq-based all-oral regimens lasting up to 12 months. Primary outcomes were treatment success rate (TSR) and incidence of serious adverse events (SAEs). We also compared efficacy and safety with longer oral or injectable regimens in control groups. Meta-analyses were conducted to pool event rates and risk ratios (RRs). Subgroup analyses and meta-regression were performed to identify potential sources of heterogeneity.
Results: Data from 12 studies involving 1902 DR-TB patients across 11 countries were analysed. The pooled TSR was 83% (95% CI 77% to 89%), with mortality, treatment failure and loss to follow-up (LTFU) rates of 5% (3-8), 4% (2-6) and 4% (2-6), respectively. Subgroup analyses showed no significant differences in TSR by DR-TB type or HIV status. The incidence rate of SAE was 19% (13-24), with prolonged corrected QT interval (QTc) in 5% (2-8) of cases. Compared with the control regimens, all-oral Bdq-based shorter regimens significantly improved treatment success (RR 1.22, 1.04-1.43) but reduced mortality (RR 0.73, 0.69-0.99), treatment failure (RR 0.33, 0.32-0.62) and QTc prolongation (RR 0.39, 0.21-0.73).
Conclusions: All-oral Bdq-based shorter regimens have improved treatment outcomes and significantly advanced DR-TB management. We urge policymakers, clinicians and stakeholders to expand access to and expedite the implementation of these regimens.
Keywords: Control strategies; Global Health; Public Health; Systematic review; Tuberculosis.
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Therapeutic Outcomes in Patients With Trichophyton indotineae: A Systematic Review and Meta-Analysis of Individual Patient Data
DOI: 10.1111/myc.70048
Authors: Charussri Leeyaphan
Abstract
Background: Trichophyton indotineae has emerged as a significant global dermatophyte, associated with recalcitrant dermatophytosis and increasing antifungal resistance.
Materials and methods: This study evaluates therapeutic outcomes in T. indotineae infections. We conducted a systematic review and meta-analysis of individual patient data adhering to PRISMA guidelines, including studies published before December 2023 from six electronic databases. Only studies with confirmed T. indotineae by rDNA sequencing and therapeutic outcome data were included.
Results: A total of 27 publications with 81 cases were included. T. indotineae infections affected both genders equally, with 25% having prior steroid use, which was significantly associated with non-improvement. Resistance to terbinafine was observed in 85.3% of cases. Oral itraconazole was significantly associated with a cure. The restricted median time to complete clinical cure was 11.50 weeks, with a recurrence rate of 19.7%.
Conclusions: The effective management of T. indotineae infections is essential, given the significant challenges posed by antifungal resistance.
Keywords: Trichophyton indotineae; dermatophytes; dermatophytosis; fungal infection.
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A randomized open label pilot study evaluating the efficacy of two dosing regimens of rifamycin SV MMX in the treatment of small intestinal bacterial overgrowth
Authors: Bradley A Connor
Abstract
Antibiotics have demonstrated efficacy in the eradication of the underlying overgrowth bacteria and improvement of symptoms of small intestinal bacterial overgrowth (SIBO). The use of standard antibiotics may cause intolerable side effects such as development of multidrug-resistant enteric bacteria, Clostridioides difficile infections and dysbiosis. Nonabsorbable antibiotics have the advantage of minimized side effects. Rifaximin, an antibiotic of the ansamycin class has been shown to be effective in the treatment of SIBO. We evaluated the use of another ansamycin antibiotic, rifamycin SV MMX (AEMCOLO) in the treatment of SIBO. One difference from rifaximin is the site of delivery of AEMCOLO which appears to be the distal small intestine and colon. Hence by maintaining the microbial milieu of the proximal small intestine, the clearance of the overgrowth bacteria might be enhanced. The side effect profile of Rifamycin SV MMX has been described elsewhere in the pivotal trials; there were no safety signals noted in this study. This randomized open label pilot study evaluated the efficacy of two dosing regimens of AEMCOLO in treating SIBO. We used a simple randomization method to assign participants into study groups. The participants included 31 patients, split between two treatment arms: one receiving the medication twice daily and the other – three times daily. The outcomes were assessed based on symptom improvement and breath test normalization. The results indicated a beneficial response with both dosing regimens leading to symptom improvement and breath test normalization. Further evaluation revealed that in the three-time daily regimen, greater symptomatic improvement was observed. For clinicians treating SIBO, this study suggests that AEMCOLO is a viable treatment option. A double-blind, placebo-controlled design will probably be necessary to ascertain the true efficacy of different dosing regimens of AEMCOLO in treating SIBO.
Trial registration: ClinicalTrials.gov NCT04501380.
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A Remote Intervention Based on mHealth and Community Health Workers for Antiretroviral Therapy Adherence in People With HIV: Pilot Randomized Controlled Trial
DOI: 10.2196/67997
Authors: Shivesh Shourya
Abstract
Background: Despite the availability of antiretroviral therapy (ART), only 66% of people with HIV in the United States achieve viral suppression, largely due to suboptimal ART adherence. Barriers such as limited access to care and forgetfulness impact adherence rates, which must be maintained at ≥95% to prevent viral load rebound. Combination interventions leveraging community health worker (CHW) support and mobile health (mHealth) technologies have the potential to overcome previously identified barriers and provide cost-effective support for improving adherence and viral suppression outcomes in people with HIV.
Objective: This pilot study aimed to evaluate the feasibility, acceptability, and preliminary efficacy of remote delivery of the Community Health Worker and mHealth to Improve Viral Suppression (CHAMPS) intervention, combining the WiseApp, CHW support, and the CleverCap smart pill bottle. A secondary aim was to gather participants’ feedback on the usability of the app and pill bottle as well as to better understand their experiences with remote study procedures.
Methods: This mixed methods pilot study involved 40 participants with HIV, who were randomly assigned to a control group (n=20, 50%) or the CHAMPS intervention (n=20, 50%) over 3 months. The intervention group participated in up to 12 sessions with CHWs and used the WiseApp, paired with a CleverCap smart pill bottle, to support ART adherence. Remote baseline and follow-up visits were conducted via Zoom and included surveys measuring adherence, self-efficacy, and usability (measured by Health Information Technology Usability Evaluation Scale [Health-ITUES] and Poststudy System Usability Questionnaire [PSSUQ]). Semistructured interviews explored participants’ experiences with the intervention. Thematic analysis was used to identify key facilitators and barriers based on the Mobile Health Technology Acceptance Model.
Results: Remote delivery of the CHAMPS intervention was feasible, with high usability ratings for both the WiseApp and CleverCap (overall scores on Health-ITUES: mean 4.35, SD 0.58 and PSSUQ: mean 2.04, SD 1.03). In the intervention group, there were nonsignificant improvements in self-reported adherence scores (P=.29) and in self-efficacy scores (P=.07). The adjusted odds ratio for achieving undetectable viral load in the intervention group compared to the control group was 3.01 (95% CI -1.59 to 4.12), indicating a medium effect size in favor of the intervention. Overall study retention was 75% (30/40), with higher retention in the control group. Participants valued the flexibility of remote study procedures, particularly Zoom-based study visits and mailed blood sample kits. Qualitative feedback highlighted the intervention’s acceptability and ability to overcome logistical barriers.
Conclusions: The remote CHAMPS pilot study demonstrated the feasibility and acceptability of combining mHealth tools with CHW support to promote medication adherence among people with HIV. While further optimization is needed to enhance its impact, this intervention shows potential for improving health outcomes in diverse underserved populations.
Trial registration: ClinicalTrials.gov NCT05938413; https://clinicaltrials.gov/study/NCT05938413.
Keywords: ART; ART adherence; CHWs; HIV; antiretroviral therapy adherence; community health workers; feasibility evaluation; mHealth technology; mobile health technology; mobile health technology acceptance model; smart pill bottle.
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Bedaquiline and linezolid regimens for multidrug-resistant tuberculosis: a systematic review and meta-analysis
Authors: Mahdis Cheraghi
Abstract
Objective: Multidrug-resistant tuberculosis (MDR-TB) remains a global public health challenge, complicating treatment strategies and requiring advanced therapeutic approaches. The persistence of MDR-TB has led to a demand for regimens that are more effective in improving treatment outcomes and controlling transmission. This systematic review and meta-analysis sought to examine the efficacy of linezolid (LZD) and bedaquiline (BDQ) in MDR-TB treatment regimens, evaluating their roles in enhancing therapeutic success and informing optimized management of MDR-TB.
Methods: A comprehensive search was conducted across MEDLINE (PubMed), EMBASE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials assessing the efficacy of LZD and BDQ in MDR-TB patients up to September 14, 2024. We analyzed treatment outcomes, reporting favorable outcomes (cured and treatment completed) and unfavorable outcomes (death, treatment failure, and loss to follow-up) with a 95% confidence interval.
Results: Our analysis included 11 trials, with a total of 1,999 participants. The findings indicate that BDQ+LZD-containing regimens yield significantly higher favorable treatment outcomes (84.5%; 95% CI, 79.8%-88.2%) and lower unfavorable outcomes (15.4%; 95% CI, 11.6%-20.2%). In contrast, regimens lacking either LZD or BDQ show lower efficacy, with favorable outcomes at 66.8% (95% CI, 59.5%-73.4%) and unfavorable outcomes at 33.0% (95% CI, 25.6%-41.4%).
Conclusions: MDR-TB treatment regimens including BDQ and LZD lead to significantly better patient outcomes. The combined bactericidal and protein synthesis-inhibiting effects of BDQ and LZD create a powerful therapeutic synergy. Adding pretomanid further enhances this effectiveness, highlighting its value in complex cases. Future research should focus on optimizing these regimens for safety and efficacy and explore adjunctive therapies to improve MDR-TB outcomes even further.
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Efficacy and metabolomic analysis of the pneumonia compound formulation against community-acquired pneumonia: an observational controlled before-after clinical trial
Authors: Ying Zhou
Abstract
Background: Pneumonia Compound Formulation (PCF) is a traditional Chinese medicine (TCM) formula used for the clinical treatment of novel coronavirus pneumonia. However, its efficacy and mechanism of action for community-acquired pneumonia (CAP) are unknown. Therefore, the aim of this study was to evaluate the efficacy of PCF combined with antibiotics in the treatment of CAP and to explore its mechanism based on metabolomics.
Patients and methods: This prospective controlled study included 100 CAP patients from June to December 2023. Patients were randomized into an antibiotics-only group (NCM, n = 50) and a combined antibiotics and PCF treatment group (CM, n = 50). Clinical data were collected for all participants. The efficacy of the treatments was assessed by comparing traditional Chinese medicine syndrome scores and clinical parameters before and after treatment. Levels of inflammatory mediators (CRP, IL-6, TNF-α) and immunoglobulins (IgA, IgG, IgM) in the plasma were measured using ELISA. Plasma metabolomics analysis was conducted using ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS).
Results: Both the NCM and CM group improved the clinical symptoms of CAP patients, with the CM group showing more significant improvements. Both groups effectively reduced the levels of the inflammatory mediators CRP, but had no significant impact on immunoglobulin levels. CM group using additional PCF significantly altered glycerophospholipid metabolism in patients, primarily characterized by increased levels of phosphatidylinositol, phosphatidylglycerol, and 1-acyl-sn-glycero-3-phosphoethanolamine, and decreased levels of phosphatidylcholine and phosphatidylethanolamine.
Conclusions: PCF is an effective adjunct therapy to antibiotics for the treatment of CAP, enhancing clinical symptom improvement. Its mechanism may involve the regulation of glycerophospholipid metabolism levels in patients, providing a new theoretical basis for the application of PCF in the treatment of CAP.
Trial registration: ChiCTR2400086283 (2024-06-27).
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Enhanced support for adherence to rheumatic heart disease prophylaxis for children in the public health system in Uganda (CAMPS): a pragmatic randomised trial
Authors: Sarah de Loizaga
Abstract
Background: Secondary antibiotic prophylaxis is the only intervention known to prevent rheumatic heart disease progression, yet delivery of prophylaxis at scale in low-resource settings has proven challenging, undermining many global programmes. We sought to assess whether enhanced prophylaxis support for rheumatic heart disease, administered through community health workers in the public health system, was feasible and a scalable model.
Methods: The CAMPS trial was a pragmatic randomised trial of prophylaxis supports integrated into routine care in Eastern Uganda. Children and adolescents with rheumatic heart disease who were aged 5-17 years were randomly assigned (1:1) using permuted block randomisation to either usual care or enhanced support. Enhanced support consisted of case managers and peer groups. Participants and providers were not masked to treatment assignment due to the study design. Children were followed up for 12 months to compare the primary outcome of prophylaxis adherence, measured as a continuous variable of days covered, using a modified intention-to-treat analysis principle. Secondary outcomes were treatment satisfaction, and patient and caregiver health-related quality of life scores. This trial is registered at ClinicalTrials.gov, NCT05502042, and has been completed.
Findings: Between Aug 9, 2022, and Aug 9, 2023, 208 individuals were enrolled in the study and included in the analysis. 104 (50%) individuals were randomly assigned to the usual care group and 105 (50%) to the enhanced support group; one participant in the usual care group was excluded from the primary analysis as they died before the first injection, meaning that 103 participants were analysed in the usual care group. 121 (58%) participants were female and 87 (42%) were male. After 12 months, mean adherence was 80·0% (SD 19·0) for those receiving usual care, compared with 98·2% (7·1) for those receiving enhanced support (estimated mean difference in adherence of 18·2%, 95% CI 14·4-22·1; p<0·0001). No significant differences were found between groups in treatment satisfaction (mean between-group difference of 0·1 points [95% CI -1·9 to 2·1] at 12 months) or quality of life (2·3 [-1·1 to 5·8] for patient score; 1·3 [-1·6 to 4·1] for caregiver score).
Interpretation: The integration of community health workers into rheumatic heart disease supports within the public health system provides an effective and likely scalable model to improve outcomes for children with rheumatic heart disease in low-resource settings. Further research should examine scale-up and scale-out of these strategies, formally explore cost, and rigorously partner with diverse groups of patients to shape adaptations to this design and ensure appropriateness for all groups affected by rheumatic heart disease.
Funding: Thrasher Research Fund Early Career Award and Edwards LifeSciences Foundation.
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External Validation of a Pharmacokinetic Model Developed for Vancomycin Administration via Target-Controlled Infusion
DOI: 10.2147/DDDT.S507377
Authors: Jung-Min Yi
Abstract
Purpose: Target-controlled infusion (TCI) could provide a patient-tailored approach for vancomycin dosing. This study aimed to externally evaluate the predictive performance of a previously constructed pharmacokinetic model of vancomycin (Choi model) specifically optimized for TCI administration of vancomycin differing from the existing model, and to assess the feasibility of administering vancomycin via TCI in clinical practice. Additionally, clinical outcomes were exploratively compared between the TCI and intermittent infusion (standard) methods for vancomycin administration.
Patients and methods: Clinically ill patients were randomly assigned in a 1:1 ratio to either the TCI or standard group. In the TCI group, vancomycin was administered using the Choi model, targeting an initial concentration of 25 mg/L, adjusted to maintain therapeutic levels (20-30 mg/L). The standard group received a loading dose of 25 mg/kg, then 15 mg/kg every 12 hours. Vancomycin concentrations for analysis were obtained from three blood samples per patient at set times, along with routine therapeutic drug monitoring data. Predictive performance was assessed using four parameters: inaccuracy, divergence, bias, and wobble. The occurrence of acute kidney injury (AKI) during and up to 7 days after vancomycin was investigated.
Results: The study was terminated early due to challenges in enrolling subjects (TCI: n=12, standard: n=13). Thirty-seven serum concentration measurements from the TCI group were analyzed. Pooled median bias and inaccuracy (95% confidence interval) were -2.7 (-7.3 to 1.9) and 17.0 (13.9 to 20.2), respectively. AKI incidence was similar between groups (TCI: n=0, standard: n=1) in this exploratory analysis, but caution is warranted in interpreting these outcomes as the planned sample size was not met.
Conclusion: The predictive performance of the TCI system integrated with the Choi model was suitable for clinical use. Further studies with a large cohort should be performed to determine the clinical effectiveness of vancomycin administered via the TCI method.
Trial registration: This study was registered at the Clinical Research Information Service of the Korean National Institute of Health (CRIS, http://cris.nih.go.kr), with registration number KCT0003462, on January 31, 2019).
Keywords: concentration; model; pharmacokinetics; predictive performance; target-concentration controlled infusion; vancomycin.