Self-controlled Study Research Articles

Enhancing nutritional management in peritoneal dialysis patients through a generative pre-trained transformers-based recipe generation tool: a pilot study

BackgroundPatients undergoing peritoneal dialysis (PD) often face nutritional deficiencies due to inadequate intake, nutrient loss, insufficient dialysis, and a state of micro-inflammatory. Traditional nutritional management methods have not fully met personalized needs. Therefore, this study aimed to develop and evaluate an application for generating recipes based on Generative Pre-trained Transformers to improve the nutritional status of these patients.MethodsThis self-controlled prospective study included 35 patients undergoing PD from January to February 2024. The study was divided into two phases: the initial phase involved conventional dietary education under PD management, followed by a second phase where a new GPT-based dietary guidance tool was introduced. Patients adhered to the diets recommended by the tool. Nutritional intervention effects were assessed by comparing serum prealbumin, albumin, and phosphate levels before and after the intervention.ResultsAfter the intervention, the mean prealbumin levels significantly improved from 289.04 ± 74.60 mg/L to 326.72 ± 78.89 mg/L (p = 0.001). Although there was no statistical significance, the serum albumin levels in patients increased from 34.70 ± 5.94 g/L to 35.66 ± 5.14 g/L (p = 0.153). Serum phosphate levels remained stable and within safe limits (p = 0.241).ConclusionThe AI-based recipe generation application significantly improved serum prealbumin levels in PD patients without causing adverse changes in phosphate levels, confirming its efficacy and safety in nutritional management for these patients. This study highlights the potential and practical value of AI technology in nutritional management for patients with chronic disease, providing important evidence for future clinical applications.

SSA-ZP on Scalp Seborrheic Dermatitis: Regulating Sebum Levels and Scalp Barrier.

The occurrence of scalp seborrheic dermatitis (SD) is closely related to the production of sebum and scalp barrier function. Supramolecular salicylic acid has the keratolytic and anti-inflammatory properties, and zinc pyrithione is an antifungal drug delivered as a microparticle to skin epithelia. This study aimed to assess the efficacy and safety of 2% supramolecular salicylic acid (SSA) combined with 0.8% zinc pyrithione conditioner (SSA-ZP) in treating scalp SD focusing on key outcome measures including sebum levels and scalp barrier function. Five patients with mild to moderate scalp SD were included in the 2-week self-controlled prospective study, receiving daily SSA-ZP treatment. Evaluation on days 0, 7, and 14 included dermoscopy, the adherent scalp flaking scale (ASFS), sebum level, transepidermal water loss (TEWL), pH, and stratum corneum hydration. We also performed the fungal count across specific scalp regions, such as the left and right sides of the forehead, the top of the head, and the occiput. Five patients with mild to moderate scalp SD participated in this study. After 2 weeks of SSA-ZP treatment, significant reductions in ASFS scores, sebum levels, and fungal count were observed, alongside improvements in TEWL and pH values across multiple scalp regions. Moreover, there was no difference in the hydration of stratum corneum. SSA-ZP demonstrated efficacy in treating scalp SD without adverse effects, suggesting its potential as a first-line treatment option. Further research with larger sample sizes and longer follow-up periods is warranted to validate these findings.

Self-control study of multi-omics in identification of microenvironment characteristics in urine of uric acid stone

AbstractThe aim of this study is to perform proteomic and metabolomic analyses in bilateral renal pelvis urine of patients with unilateral uric acid kidney stones to identify the specific urinary environment associated with uric acid stone formation. Using cystoscopy-guided insertion of ureteral catheters, bilateral renal pelvis urine samples are collected. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is employed to identify differentially expressed proteins and metabolites in the urine environment. Differentially expressed proteins and metabolites are further analyzed for their biological functions and potential metabolic pathways through Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. In the urine from the stone-affected side, eight differential proteins were significantly upregulated, and six metabolites were dysregulated. The uric acid stone urinary environment showed an excess of α-ketoisovaleric acid and 3-methyl-2-oxovaleric acid, which may contribute to the acidification of the urine. Functional and pathway analyses indicate that the dysregulated metabolites are mainly associated with insulin resistance and branched chain amino acid metabolism.

Risk of major adverse cerebro-cardiovascular events following BNT162b2, CoronaVac, and ChAdOx1 vaccination and SARS-CoV-2 infection: A self-controlled case-series study

ObjectiveTo assess the potential risk of major adverse cerebro-cardiovascular events (MACCE) associated with COVID-19 vaccination and SARS-CoV-2 infection. MethodsThis self-controlled case series study used nationwide health database from Malaysia. The study included individuals aged ≥18 years who were hospitalised between 24 February 2021 and 30 June 2022. Outcomes were composite of MACCE: stroke, acute ischaemic heart disease, and cardiovascular death. Exposures were COVID-19 vaccination and SARS-CoV-2 infection. The risk period was day 1 to day 21 following exposure. Conditional Poisson regression model was used to estimate the incidence rate ratios (IRRs) and 95 % confidence interval (CI) comparing the outcomes in the risk and control periods. ResultsThe risk of MACCE within 21 days after vaccination per 100,000 doses administered were 12.0 (95% CI 11.9–12.1) (BNT162b2), 9.2 (95% CI 9.1–9.3) (CoronaVac), and 6.8 (95% CI 6.6–7.0) (ChAdOx1). The incidence rate ratios showed no increased risk of MACCE associated with the first, second, or third doses of BNT162b2, CoronaVac, and ChAdOx1 vaccines for individuals without prior cardiovascular disease (CVD). This finding was consistent for individuals with CVD. Vaccine booster dose, whether in a homologous or heterologous schedule, did not show increased risk of MACCE. Analysis by ethnic groups detected a slightly elevated risk of MACCE in Indian after the first dose of ChAdOx1 (IRR 1.64; 95% CI 1.08–2.48) in those without CVD. No significant association were observed in other subgroup analyses. SARS-CoV-2 infection was associated with significantly increased risk of MACCE in individuals without CVD (IRR 3.54; 95% CI 3.32–3.76) and with CVD (IRR 1.98; 95% CI 1.61–2.34). ConclusionsOur findings support the favourable safety profile of these COVID-19 vaccines and indicate that the overall benefit-risk ratio of the COVID-19 vaccines remains positive.

Immediate modulatory effects of transcutaneous vagus nerve stimulation on patients with Parkinson's disease: a crossover self-controlled fMRI study.

Previous studies have evaluated the safety and efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) for the treatment of Parkinson's disease (PD). However, the mechanism underlying the effect of taVNS on PD remains to be elucidated. This study aimed to investigate the immediate effects of taVNS in PD patients. This crossover self-controlled study included 50 PD patients. Each patient underwent three sessions of resting-state functional magnetic resonance imaging (rs-fMRI) under three conditions: real taVNS, sham taVNS, and no taVNS intervention. We analyzed whole-brain amplitude of low-frequency fluctuations (ALFF) from preprocessed fMRI data across different intervention conditions. ALFF values in altered brain regions were correlated with clinical symptoms in PD patients. Forty-seven participants completed the study and were included in the final analysis. Real taVNS was associated with a widespread decrease in ALFF in the right hemisphere, including the superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus (voxel p < 0.001, GRF corrected). The ALFF value in the right superior parietal lobule during real taVNS was negatively correlated with the Unified Parkinson's Disease Rating Scale Part III (r = -0.417, p = 0.004, Bonferroni corrected). TaVNS could immediately modulate the functional activity of brain regions involved in superior parietal lobule, precentral gyrus, postcentral gyrus, middle occipital gyrus, and cuneus. These findings offer preliminary insights into the mechanism of taVNS in treating PD and bolster confidence in its long-term therapeutic potential. TaVNS appears to reduce ALFF values in specific brain regions, suggesting a potential modulation mechanism for treating PD.

Epidemiological study of the relationship between meteorological factors and onset of acute aortic dissection in Japan.

Several factors influence the onset of acute aortic dissection (AAD). However, few studies have examined AAD onset, weather conditions, and meteorological factors in Japan. This study aimed to identify meteorological factors associated with the onset of AAD in Japan. In this self-controlled study, patients diagnosed with AAD onset from May 1, 2012, to April 30, 2021, at Shizuoka City Shizuoka Hospital (Shizuoka, Japan) were included. Meteorological data from the Shizuoka District Meteorological Office were used. Control days were randomly selected from a 29-day period centered on the day of onset. Conditional logistic regression models were used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) for the onset of AAD relative to the control day due to changes in meteorological factors. In total, 538 patients were included. The meteorological factors associated with the onset of AAD were identified as the daily mean temperature (OR = 1.10; 95% CI = 1.04-1.16), daily minimum temperature (OR = 1.09; 95% CI = 1.03-1.14), daily maximum temperature (OR = 1.05; 95% CI = 1.00-1.10), and the mean of the daily mean temperatures for the previous 7 days (OR = 1.17; 95% CI = 1.07-1.28) with a 1°C decrease in the temperature. The results of this study are expected to help raise awareness in clinical practice and among the general public about the increased risk of AAD associated with a drop in temperature.

Salivary microbiota composition before and after use of proton pump inhibitors in patients with laryngopharyngeal reflux: a self-control study

BackgroundIssues associated with proton pump inhibitor (PPI) usage have been documented. PPIs affect the gastrointestinal microbiome, as well as the saliva microbiota of healthy individuals. However, the alterations in the saliva microbiota of laryngopharyngeal reflux (LPR) patients remain unclear. This study aims to examine the composition of saliva microbiota in LPR patients before and after PPI usage through a self-controlled study.MethodsThirty-two adult LPR patients participated in the study. Saliva samples were collected before and after an 8-week regimen of twice-daily administration of 20-mg esomeprazole. The impact of PPI administration on bacterial communities was assessed using 16 S rRNA gene sequencing. The functional and metabolic changes in saliva microbial communities after PPI usage were analyzed using PICRUSt2 based on our 16 S rRNA gene sequencing results.ResultsThe alpha diversity within the salivary microbiota, as measured by the PD-whole-tree index, exhibited a significant difference between samples collected before and after PPI application (P = 0.038). Additionally, PCoA analysis of unweighted UniFrac distances (beta diversity) revealed distinct separation of saliva sample microbiota structures before and after PPI application in LPR patients, with statistical significance (Adonis test, R2 = 0.063, P< 0.010). Taxon-based analysis indicated that PPI administration increased the abundance of Epsilonproteobacteria, Campylobacterales, Campylobacteraceae, Campylobacter, and Campylobacter_gracilis, while reducing the abundance of Lactobacillaceae and Lactobacillus in salivary samples ( P< 0.050). Using LEfSe to compare bacterial abundances, Bacillaceae and Anoxybacillus were found to be enriched before PPI usage in LPR patients. Furthermore, the proportion of genes responsible for indole alkaloid biosynthesis in the salivary microbiota of LPR patients significantly increased after PPI therapy (P< 0.050).ConclusionsThese findings indicate that PPIs induce alterations in the salivary microbiota of LPR patients.Chinese clinical trial registryNo. ChiCTR2300067507. Registered on January 10,2023 retrospectively.Level of evidence4.

Risk for Facial Palsy after COVID-19 Vaccination, South Korea, 2021-2022.

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

CHIEF: A retrospective self-control study of children with severe hemophilia A without inhibitors comparing emicizumab to FVIII prophylaxis.

Hemophilia A (HA) is an X-linked bleeding disorder diagnosed by a deficiency in factor VIII (FVIII). For severe HA (SHA), prophylaxis clotting factor concentrates (CFC) has become the standard of care; however, it imparts a high treatment burden and typically results in an annualized bleeding rate (ABR) of 2-6. Emicizumab, a subcutaneously administered FVIII substitute, has become the de facto standard-of-care prophylaxis for children with SHA in many countries. Previous clinical trials of emicizumab have assessed ABR in patients greater than 12years without inhibitors, and in children less than 12years with inhibitors; however, there is little information published regarding the ABR of emicizumab compared to CFC in non-inhibitor SHA children. Using a retrospective electronic medical record chart review, we conducted a self-control analysis of 15 patients less than 12years of age during equivalent periods of CFC versus emicizumab prophylaxis. The mean ABR on CFC and emicizumab was 1.79 and 1.13 (p=.092), respectively, with a substantially decreased rate of joint bleeds (CFC 0.94; emicizumab 0.33; p=.001) and spontaneous bleeds (CFC 0.79; emicizumab 0.23; p=.008). No safety events were recorded for patients while administering emicizumab. The mean annual cost of CFC prophylaxis was $515,340 (SD $199,540), compared to $328,410 (SD $137,230) for emicizumab prophylaxis (p<.001). Emicizumab resulted in an improved ABR compared to CFC, especially for joint and spontaneous bleeds, had fewer administration complications, and was substantially less expensive compared to CFC prophylaxis; however, more research is necessary for a complete understanding of the effect of emicizumab on joint health and muscle bleeds.

Relationship between proton pump inhibitor prescription and asthma exacerbation among adult patients: a self-controlled case series study.

Proton-pump inhibitors (PPI) are empirically used to treat asthma symptoms such as cough; however, the effectiveness of PPI on asthma exacerbation has not been well studied. We aimed to evaluate the relationship between PPI use and asthma exacerbation using a large administrative claims database in Japan. We conducted a self-controlled case series using the JMDC Claims Database (JMDC, Inc., Tokyo, Japan). The cases included adult patients with asthma who were prescribed PPI and experienced at least one outcome event between January 2015 and December 2019. The primary outcome was the composite outcome of hospital admissions and unscheduled outpatient clinic visits due to asthma exacerbation. We also conducted stratified analyses based on PPI generation, the presence of gastroesophageal reflux disease (GERD), asthma severity, and the number of allergic comorbidities. A total of 7379 eligible patients were included in the study. PPI prescription was associated with a decrease in the composite outcomes (incidence rate ratio, 0.90; 95% confidence interval, 0.87-0.93). However, PPI prescriptions did not affect the outcomes of hospital admissions (incidence rate ratio, 1.34; 95% confidence interval, 0.86-2.10). Stratified analyses based on PPI generation, the presence of GERD, asthma severity (except for severe asthma), and the number of allergic comorbidities yielded consistent results. PPI use was associated with a moderate decrease in asthma exacerbation, regardless of the patient profile. However, this effect was not as strong as the prevention of hospital admissions, and outcome events were not prevented in patients with severe asthma.

Human papillomavirus nonavalent (HPV9) vaccination and risk of immune mediated diseases, myocarditis, pericarditis, and thromboembolic outcomes in Denmark: self-controlled case series study

ObjectiveTo assess the associations between vaccination with the nonavalent human papillomavirus (HPV9) vaccine and immune mediated diseases, myocarditis, pericarditis, arterial thromboembolism, and venous thromboembolism with or without thrombocytopenia, in adolescent...

Can combined tomosynthesis with unenhanced MRI be used as a predictive tool for lymphovascular invasion?

BackgroundThe presence of lymphovascular invasion (LVI) in cases with breast cancer is considered a bad prognostic sign. The purpose of this study is to compare the efficacy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) versus unenhanced magnetic resonance imaging (UE-MRI + DBT) in predicting LVI in women with pathologically confirmed breast cancer.MethodsThis prospective self-controlled study enrolled a total of 70 cases of pathologically proven breast cancer. All the patients underwent tomosynthesis, non-contrast, and post-contrast MRI. Depending on the broken halo sign seen in tomosynthesis, peritumoral edema, dark rim diffusion at diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) values evaluated in MRI.ResultsThe accuracy of LVI detection by tomosynthesis was 58%; unenhanced and enhanced MRI had the same results at 60%. The accuracy of detecting LVI was raised to 64% by combining the tomosynthesis results with unenhanced MRI.ConclusionsTomosynthesis parameters are promising tools in detecting LVI in breast cancer with better diagnostic accuracy in combination with unenhanced MRI.

Correction of Presbyopia by Monocular Bi-Aspheric Ablation Profile.

The study aims to evaluate visual acuity and objective visual quality before and after the monocular bi-aspheric ablation profile for correction of presbyopia surgery. This prospective self-control study included 20 cases and 38 eyes of patients who underwent monocular bi-aspheric ablation profile correction of myopia with presbyopia at the Eye Hospital of Shandong University of Traditional Chinese Medicine from January 2023 to January 2024. These patients were selected for observation, and each patient's preoperative and postoperative uncorrected distance visual acuity (UDVA), uncorrected near visual acuity (UNVA), corrected distance visual acuity (CDVA), spherical aberration (SA) (within 6 mm), horizontal and vertical coma (within 6 mm), and corneal aspheric index (Q-value) (within 6 mm) were evaluated. Statistical data analysis was performed at different time points before and after the operation. There were statistically significant differences in UDVA between dominant and non-dominant eyes before and after surgery (Z = -3.784, p < 0.001; Z = -3.817, p < 0.001). Post-operatively, 90% of the non-dominant eyes achieved UNVA of J1 and above, and 95% of the bilateral eyes achieved UNVA of J1 and above. Significant differences were found in the SA of the dominant eyes, which showed a positive increase (Z= -3.784, p < 0.001); however, compared with the dominant eye, the SA of the non-dominant eye was negatively increased, but the difference was not statistically significant (p = 0.08). There was a significant difference in the vertical coma of the dominant eye before and after the operation, but there was no significant difference in non-dominant eyes. There was no significant difference in the change of binocular horizontal coma before and after the operation. There were significant changes in the Q value of both eyes before and after the operation (Z = -3.923, p < 0.001; Z = -3.51, p < 0.001). After the monocular bi-aspheric ablation profile, the cornea of the non-dominant eye showed a prolate shape, negative SA increased, and the UDVA and UNVA improved after the operation.

Foundational model aided automatic high-throughput drug screening using self-controlled cohort study.

Developing medicine from scratch to governmental authorization and detecting adverse drug reactions (ADR) have barely been economical, expeditious, and risk-averse investments. The availability of large-scale observational healthcare databases and the popularity of large language models offer an unparalleled opportunity to enable automatic high-throughput drug screening for both repurposing and pharmacovigilance. To demonstrate a general workflow for automatic high-throughput drug screening with the following advantages: (i) the association of various exposure on diseases can be estimated; (ii) both repurposing and pharmacovigilance are integrated; (iii) accurate exposure length for each prescription is parsed from clinical texts; (iv) intrinsic relationship between drugs and diseases are removed jointly by bioinformatic mapping and large language model - ChatGPT; (v) causal-wise interpretations for incidence rate contrasts are provided. Using a self-controlled cohort study design where subjects serve as their own control group, we tested the intention-to-treat association between medications on the incidence of diseases. Exposure length for each prescription is determined by parsing common dosages in English free text into a structured format. Exposure period starts from initial prescription to treatment discontinuation. A same exposure length preceding initial treatment is the control period. Clinical outcomes and categories are identified using existing phenotyping algorithms. Incident rate ratios (IRR) are tested using uniformly most powerful (UMP) unbiased tests. We assessed 3,444 medications on 276 diseases on 6,613,198 patients from the Clinical Practice Research Datalink (CPRD), an UK primary care electronic health records (EHR) spanning from 1987 to 2018. Due to the built-in selection bias of self-controlled cohort studies, ingredients-disease pairs confounded by deterministic medical relationships are removed by existing map from RxNorm and nonexistent maps by calling ChatGPT. A total of 16,901 drug-disease pairs reveals significant risk reduction, which can be considered as candidates for repurposing, while a total of 11,089 pairs showed significant risk increase, where drug safety might be of a concern instead. This work developed a data-driven, nonparametric, hypothesis generating, and automatic high-throughput workflow, which reveals the potential of natural language processing in pharmacoepidemiology. We demonstrate the paradigm to a large observational health dataset to help discover potential novel therapies and adverse drug effects. The framework of this study can be extended to other observational medical databases.

Achieving sub-millisievert CT colonography for accurate colorectal tumor detection using smart examination protocols: a prospective self-controlled study.

To assess the feasibility of combining Auto-kVp selection technique, higher preset ASIR-V and noise index (NI) to realize individualized sub-mSv CT colonography (CTC) for accurate colorectal tumor detection and localization. Ninety patients with suspected colorectal cancer (CRC) were prospectively enrolled to undergo standard dose CTC (SDCTC) in the prone and ultra-low dose CTC (ULDCTC) in the supine position. SDCTC used 120 kVp, preset ASIR-V of 30%, SmartmA for a NI of 13; ULDCTC used Auto-kVp selection technique with 80 or 100 kVp, preset ASIR-V of 60%, SmartmA for a NI of 13 for 80 kVp, and NI of 15 for 100 kVp. The effective dose (ED), image quality [signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of colorectal neoplasms] between the two protocols were compared and the accuracies of tumor locations were evaluated for CTC in comparison with the surgery results. The mean ED of the ULDCTC-80 kVp subgroup was 0.70 mSv, 71.43% lower than the 2.45mSv for the 120 kVp group, while that of the ULDCTC-100 kVp subgroup was 0.98mSv, 73.00% lower than the 3.63mSv for the 120 kVp group (P < 0.001). The tumor SNR and CNR of the ULDCTC were higher than those of SDCTC (P < 0.05), while there was no difference in the subjective image quality between them with good inter-observer agreement (Kappa: 0.805-0.923). Both SDCTC and ULDCTC groups had high detection rate of colorectal tumors, along with good consistency in determining tumor location compared with surgery reports (Kappa: 0.718-0.989). The combination of Auto-kVp selection, higher preset ASIR-V and NI achieves individualized sub-mSv CTC with good performance in detecting and locating CRC with surgery and consistent results between SDCTC and ULDCTC.

The effectiveness of a disaster preparedness educational intervention for wheelchair users: A pilot study

ObjectiveThis pilot study aimed to test the effectiveness of disaster preparedness education for wheelchair users and improve their self-management skills during emergencies. MethodsA pre-post self-controlled experimental study was conducted. The intervention included one educational session covering the following: (1) Knowledge about local frequent disasters,. (2) Development of a tailored disaster preparedness plan for wheelchair users. (3) Preparation of a disaster kit. The methods included lectures, discussions, and scenario responses to disasters. Disaster preparedness knowledge, attitudes, and behaviors were assessed before, after and one month follw-up intervention. Results20 wheelchair users with average age of 41.2 ± 7.68. Most of them reported proficiency in wheelchair using. The educational intervention significantly improved knowledge and attitude scores post-intervention, with knowledge scores rising from 8.00 ± 2.25 to 13.85 ± 0.37 and attitude scores from 47.05 ± 6.45 to 52.30 ± 3.87. At the one-month follow-up, there was a slight regression in knowledge(11.00 ± 1.65) and attitude scores(50.70 ± 3.94) but still significantly higher than pre-intervention levels. Behavior scores were assessed only at pre and follow-up measurement points, with an increasing trend from 3.60 ± 1.93 to 8.60 ± 2.89, indicating sustained improvement in disaster preparedness behaviors. The study highlights the need for sustainable intervention methods due to the observed decline in knowledge retention and attitude over time. ConclusionThe tailored disaster preparedness education for wheelchair users significantly improved their knowledge, fostered positive attitudes, and encouraged proactive behaviors in response to disasters. To sustain these positive outcomes, ongoing educational reinforcement and periodic updates are essential, especially for vulnerable populations like wheelchair users.

An investigation into the correlation between intraperitoneal teicoplanin concentrations and treatment outcomes in peritoneal dialysis-associated peritonitis.

Peritoneal dialysis-associated peritonitis (PDAP) is a frequent complication of peritoneal dialysis. The guidelines from the International Society for Peritoneal Dialysis (ISPD) suggest administering teicoplanin through the peritoneal route to treat PDAP, but do not specify the ideal concentration for peritoneal dialysis effluent (PDE). Patients meeting the trial criteria for PDAP in our hospital between July 2022 and December 2023 were enrolled. Data on PDE white blood cell count, PDE neutrophil percentage, clinical symptoms, CRP, and PCT were gathered pre- and post-treatment. Incidences of adverse drug reaction (ADR) and case numbers during treatment were recorded. Subsequently, patients were categorized into cured and uncured groups for evaluating the relationship between PDE teicoplanin concentration and treatment effectiveness. The self-control study results on teicoplanin efficacy indicated intraperitoneal teicoplanin administration achieved an efficacy rate of 88.9% and an ADR incidence of 5.5% in treating PDAP patients. There was no observed correlation between teicoplanin blood concentration and PDE concentration. PDE teicoplanin concentrations on days 1, 3, 5, and 7 post-dosing were higher inthe cured group, with a significant contrast in PDE concentration on day 5 between the 18.98 ± 2.43mg/L of the cured group and the 12.07 ± 2.68mg/L of the uncured group. ROC curve revealed a higher likelihood of cure in patients when PDE teicoplanin concentration exceeded 15.138mg/L on day 5 post-dosing. Univariate and multifactorial studies identified 24-h urine volume and the number of daily abdominal dialysis sessions as influential factors in PDE teicoplanin concentration on day 5. A positive correlation was found between 24-h urine volume and PDE teicoplanin concentration, with PDAP patients having urine volume over 537mL showing significantly higher drug concentrations. Conversely, the number of daily PDAP sessions was negatively correlated with PDE teicoplanin concentrations, indicating that patients with 1∼3 daily PDAP sessions had notably higher PDE teicoplanin concentrations compared to those with 4∼6 sessions. Therefore, PDAP patients who use intraperitoneal teicoplanin could effectively control infection by monitoring the PDE teicoplanin concentration (>15.138mg/L) on day 5 after dosing.

Drug-drug interaction between diltiazem and tacrolimus in relation to CYP3A5 genotype status in Chinese pediatric patients with nephrotic range proteinuria: a retrospective study.

Tacrolimus is widely used to treat pediatric nephrotic range proteinuria (NRP). Diltiazem, a CYP3A4/5 inhibitor, is often administered with tacrolimus, affecting its pharmacokinetic profile. The impact of this combination on tacrolimus exposure, particularly in CYP3A5*3 genetic polymorphism, remains unclear in pediatric NRP patients. This study aimed to evaluate the effects of diltiazem on tacrolimus pharmacokinetics, focusing on the CYP3A5*3 polymorphism. We conducted a retrospective clinical study involving pediatric NRP patients, divided into two groups: those receiving tacrolimus with diltiazem and those receiving tacrolimus alone. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. We compared daily dose-adjusted trough concentrations (C0/D) of tacrolimus in both the original and PSM cohorts. The influence of diltiazem on tacrolimus C0/D, stratified by CYP3A5*3 genetic polymorphism, was assessed in a self-controlled case series study. Before PSM, the tacrolimus C0/D in patients taking diltiazem was significantly higher compared to those with tacrolimus alone (75.84 vs. 56.86ng/mL per mg/kg, P = 0.034). This finding persisted after PSM (75.84 vs. 46.93ng/mL per mg/kg, P= 0.028). In the self-controlled case study, tacrolimus C0/D elevated about twofold (75.84 vs. 34.76ng/mL per mg/kg, P < 0.001) after diltiazem administration. CYP3A5 expressers (CYP3A5*1/*1 and *1/*3) and CYP3A5 non-expressers (CYP3A5*3/*3) experienced a 1.8-fold and 1.3-fold increase in tacrolimus C0/D when combined with diltiazem, respectively. Diltiazem significantly increased tacrolimus C0/D, with CYP3A5*3 expressers showing higher elevations than non-expressers among pediatric NRP patients. These findings highlight the importance of personalized tacrolimus therapy based on CYP3A5*3 genotypes in pediatric patients taking diltiazem.

Ocular Adverse Events After Influenza Vaccination in Older Adults: Self-Controlled Case Series Using a Large Database in Japan

ABSTRACT Background To clarify the risk of adverse ocular events following influenza vaccination. Methods This self-controlled case series study used a claims database linked to vaccination records of a large city in Japan between April 2014 and September 2021. Individuals aged ≥ 65 years who developed adverse ocular events during the follow-up period were included. The exposure was influenza vaccination. The primary outcome was defined as the occurrence of at least one of the following five eye diseases: uveitis, scleritis, retinal vein occlusion, retinal artery occlusion, or optic neuritis. Conditional Poisson regression was used to estimate the within-subject incidence rate ratio of ocular adverse events during the risk period (0–56 days after vaccination) compared to the control period. Results A total of 4,527 cases were eligible for the study (median age, 74 years; male, 42%). The incidence rate ratio for the outcome during the risk period was 0.99 (95% confidence interval, 0.87 to 1.14). No increased risk was observed for individual components of the outcome either; the incidence rate ratio was 0.94 (0.78 to 1.13) for uveitis, 1.17 (0.86 to 1.59) for scleritis, 0.98 (0.76 to 1.27) for retinal vein occlusion, 0.89 (0.42 to 1.87) for retinal artery occlusion, and 0.87 (0.44 to 1.70) for optic neuritis. Conclusions This self-controlled case series showed no apparent increase in the risk of adverse ocular events after influenza vaccination among older adults. These results mitigate the concerns of older adults who may hesitate to receive influenza vaccination for fear of adverse ocular events. Abbreviation HR = hazard ratio; CI = confidence interval; RVO = retinal vein occlusion; SCCS = self-controlled case series

Umbilical cord mesenchymal stem cells in ulcerative colitis treatment: efficacy and possible mechanisms

BackgroundMesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms.MethodsThis prospective, self-controlled clinical study was conducted at Henan Provincial People’s Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 106 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation.ResultsForty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy.ConclusionUMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines.Trial registrationThe study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019.