IgLON5 autoimmunity in a patient with Creutzfeldt-Jakob disease: case report and review of literature.

Objective: We present the case of a patient with clinical and imaging features of sporadic Creutzfeldt-Jakob disease (sCJD) and positive IgLON5 antibodies (Abs) in the serum and CSF. Case report: A 66-year-old Chinese man presented to the hospital with a stroke-like episode, followed by rapidly progressive cognitive decline, mutism, and parkinsonism. The MRI results showed a cortical ribboning sign in diffusion-weighted MRI, periodic triphasic waves with a slow background in EEG, and positive protein 14-3-3 in CSF. There were matching IgLON5 Abs in the serum and CSF. A literature review showed positive autoimmune encephalitis Abs or autoimmune inflammatory disease between 0.5 and 8.6% among patients with clinical suspicion of CJD, most commonly anti-voltage-gated potassium channel (VGKC) complex and anti-N-methyl-D-aspartate receptor (NMDAR) Abs; however, IgLON5 autoimmunity in CJD has been rarely reported. This is an intriguing association as both conditions have been associated with brain deposits of phosphorylated tau protein. Conclusion: IgLON5 Abs may be observed in patients with a diagnosis of CJD; it is unknown whether a synergistic effect of IgLON5 Abs with CJD exists, increasing neurodegenerative changes.

Theory-based interventions aimed at promoting physical activity in pregnant women: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: The objectives were to assess (i) the quality of theory implementation, (ii) the application of behavior change techniques, and (iii) the effectiveness of theory-based interventions in promoting physical activity in pregnant women and improving maternal and neonatal outcomes. METHODS: A systematic search was conducted across 8 databases (Cumulative Index to Nursing and Allied Health Literature, the Cochrane Library, EMBASE, MEDLINE, APA PsycINFO, PubMed, SPORTDiscus, and Web of Science) to identify randomized controlled trials published from database inception to 8 July 2023. The Cochrane risk-of-bias 2.0 tool was used to evaluate the quality of the included studies. The theory coding scheme was used to measure the quality of theory implementation, and behavior change techniques were coded according to behavior change taxonomy (version 1). The meta-analysis was performed using RevMan 5.3. The Grading of Recommendations, Assessment, Development, and Evaluation Approach was used to assess the certainty of evidence. RESULTS: Eleven studies met the study criteria. Nine studies were based on one theory, while two studies were based on a combination of two theories. The quality of theory implementation was generally moderate. A total of 24 unique behavior change techniques were extracted. The most commonly used types of behavior change techniques were 'instruction on how to perform the behavior' (n = 9), 'goal setting' (behavior) (n = 8), 'action planning' (n = 7), and 'information about health consequences' (n = 7). Theory-based interventions significantly improved moderate-to-vigorous physical activity (standardized mean difference (SMD) = 0.17, 95 % confidence interval (CI) [0.04, 0.30], P = 0.01; moderate certainty of evidence), reduced the average gestational weight gain per week (mean difference (MD) = -0.06, 95 % CI [-0.11, -0.01], P = 0.02; moderate certainty of evidence), and decreased the incidence of gestational diabetes mellitus (risk ratio (RR) = 0.64, 95 % CI [0.46, 0.89], P = 0.008; high certainty of evidence). However, the effects of theory-based interventions on total physical activity, total gestational weight gain and the incidence of gestational hypertension and preterm delivery were unclear (P > 0.05). CONCLUSIONS: (i) Most of the studies exhibited a moderate level of theory implementation quality. (ii) The use of theories varies, but common behavior change techniques were found across studies. (iii) Theory-based interventions can improve physical activity and maternal and neonatal outcomes and appear to be safe. Appropriate health behavior theories and behavior change techniques should be fully utilized in future interventions. REGISTRATION: PROSPERO: CRD42023440886. TWEETABLE ABSTRACT: Theory-based interventions can improve physical activity and maternal and neonatal outcomes and appear to be safe. Appropriate health behavior theories and behavior change techniques should be fully utilized in the development of future interventions.

[Evidence mapping of Chinese patent medicines in treatment of premature ventricular contractions].

This study employed evidence mapping to systematically sort out the clinical studies about the treatment of premature ventricular contractions with Chinese patent medicines and to reveal the distribution of evidence in this field. The articles about the treatment of premature ventricular contractions with Chinese patent medicines were searched against PubMed, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP with the time interval from January 2016 to December 2022. Evidence was analyzed and presented by charts and graphs combined with text. According to the inclusion and exclusion criteria, 164 papers were included, including 147 interventional studies, 4 observational studies, and 13 systematic reviews. A total of 27 Chinese patent medicines were involved, in which Shensong Yangxin Capsules and Wenxin Granules had high frequency. There were off-label uses in clinical practice. In recent years, the number of articles published in this field showed a decreasing trend. Eight types of outcome indicators were used in interventional studies. Ambulatory electrocardiography, clinical response rate, safety, and echocardiography had high frequency, while the rate of ß-blocker decompensation, major cardiovascular events, and pharmaceutical economic indicators were rarely reported. The evaluation was one-sided. The low quality of the included articles reduced the reliability of the findings. In the future, the clinical use of medicines should be standardized, and the quality of clinical studies should be improved. Comprehensive clinical evaluation should be carried out to provide a sound scientific basis for the treatment of premature ventricular contractions with Chinese patent medicines.

ConvNeXt-MHC: improving MHC-peptide affinity prediction by structure-derived degenerate coding and the ConvNeXt model.

Peptide binding to major histocompatibility complex (MHC) proteins plays a critical role in T-cell recognition and the specificity of the immune response. Experimental validation such peptides is extremely resource-intensive. As a result, accurate computational prediction of binding peptides is highly important, particularly in the context of cancer immunotherapy applications, such as the identification of neoantigens. In recent years, there is a significant need to continually improve the existing prediction methods to meet the demands of this field. We developed ConvNeXt-MHC, a method for predicting MHC-I-peptide binding affinity. It introduces a degenerate encoding approach to enhance well-established panspecific methods and integrates transfer learning and semi-supervised learning methods into the cutting-edge deep learning framework ConvNeXt. Comprehensive benchmark results demonstrate that ConvNeXt-MHC outperforms state-of-the-art methods in terms of accuracy. We expect that ConvNeXt-MHC will help us foster new discoveries in the field of immunoinformatics in the distant future. We constructed a user-friendly website at http://www.combio-lezhang.online/predict/, where users can access our data and application.

The correlation between iodine and metabolism: a review.

Iodine is involved in the synthesis of thyroid hormones and plays a crucial role in human life. Both iodine deficiency and excess are common issues in certain populations. Iodine also has extrathyroidal effects on organs that can uptake it independently of thyroid hormones. Recently, multiple clinical studies have shown a connection between iodine intake and metabolic disorders, such as metabolic syndrome, obesity, diabetes, hypertension, and dyslipidemia. However, the results of these studies have been inconsistent, and the mechanisms behind these associations are still not well understood. Therefore, in this review, we aim to examine the recent research progress regarding the relationship between iodine and metabolic disorders, along with the relevant mechanisms.

Chemical and linguistic considerations for encoding Chinese characters: an embodiment using chain-end degradable sequence-defined oligourethanes created by consecutive solid phase click chemistry.

Sequence-defined polymers (SDPs) are currently being investigated for use as information storage media. As the number of monomers in the SDPs increases, with a corresponding increase in mathematical base, the use of tandem-MS for de novo sequencing becomes more challenging. In contrast, chain-end degradation routines are truly de novo, potentially allowing very large mathematical bases for encoding. While alphabetic scripts have a few dozen symbols, logographic scripts, such as Chinese, can have several thousand symbols. Using a new in situ consecutive click reaction approach on an oligourethane backbone for writing, and a previously reported chain-end degradation routine for reading, we encoded/decoded a confucius proverb written in Chinese characters using two encoding schemes: Unicode and Zhèng Ma. Unicode is an internationally standardized arbitrary string of hexadecimal (base-16) symbols which efficiently encodes uniquely identifiable symbols but requires complete fidelity of transmission, or context-based inferential strategies to be interpreted. The Zhèng Ma approach encodes with a base-26 system using the visual characteristics and internal composition of Chinese characters themselves, which leads to greater ambiguity of encoded strings, but more robust retrievability of information from partial or corrupted encodings. The application of information-encoded oligourethanes to two different encoding systems allowed us to establish their flexibility and versatility for data storage. We found the oligourethanes immensely adaptable to both encoding schemes for Chinese characters, and we highlight the expected tradeoff between the efficiency and uniqueness of Unicode encoding on the one hand, and the fidelity to a scripts' particular visual characteristics on the other.

Does the Dose of Standard Adjuvant Chemotherapy Affect the Triple-negative Breast Cancer Benefit from Extended Capecitabine Metronomic Therapy? An Exploratory Analysis of the SYSUCC-001 Trial.

Purpose: Results from studies of extended capecitabine after the standard adjuvant chemotherapy in early stage triple-negative breast cancer (TNBC) were inconsistent, and only low-dose capecitabine from the SYSUCC-001 trial improved disease-free survival (DFS). Adjustment of the conventional adjuvant chemotherapy doses affect the prognosis and may affect the efficacy of subsequent treatments. This study investigated whether the survival benefit of the SYSUCC-001 trial was affected by dose adjustment of the standard adjuvant chemotherapy or not. Patients and Methods: We reviewed the adjuvant chemotherapy regimens before the extended capecitabine in the SYSUCC-001 trial. Patients were classified into "consistent" (standard acceptable dose) and "inconsistent" (doses lower than acceptable dose) dose based on the minimum acceptable dose range in the landmark clinical trials. Cox proportional hazards model was used to investigate the impact of dose on the survival outcomes. Results: All 434 patients in SYSUCC-001 trial were enrolled in this study. Most of patients administered the anthracycline-taxane regimen accounted for 88.94%. Among patients in the "inconsistent" dose, 60.8% and 47% received lower doses of anthracycline and taxane separately. In the observation group, the "inconsistent" dose of anthracycline and taxane did not affect DFS compared with the "consistent" dose. Moreover, in the capecitabine group, the "inconsistent" anthracycline dose did not affect DFS compared with the "consistent" dose. However, patients with "consistent" taxane doses benefited significantly from extended capecitabine (P=0.014). The sufficient dose of adjuvant taxane had a positive effect of extended capecitabine (hazard ratio [HR] 2.04; 95% confidence interval [CI] 1.02 to 4.06). Conclusion: This study found the dose reduction of adjuvant taxane might negatively impact the efficacy of capecitabine. Therefore, the reduction of anthracycline dose over paclitaxel should be given priority during conventional adjuvant chemotherapy, if patients need dose reduction and plan for extended capecitabine.

circTADA2A inhibited SLC38A1 expression and suppresses melanoma progression through the prevention of CNBP trans-activation.

BACKGROUND: CircTADA2A has been demonstrated to play critical roles in the occurrence and development of human cancer. However, the expression pattern and biological mechanisms of circTADA2A in melanoma remains largely unknown. METHODS: CircTADA2A were detected by quantitative real-time RT-PCR (qRT-PCR) and validated by Sanger sequencing. Function of circTADA2A and its protein partner in melanoma cells was investigated using RNA interference and overexpression assays. Interaction of circTADA2A, CCHC-type zinc finger nucleic acid binding protein (CNBP) and solute carrier family 38 member 1 (SLC38A1) was confirmed by RNA immunoprecipitation, RNA pull-down, and dual-luciferase reporter assay. The expression of genes and proteins were detected by qRT-PCR and western blot assays. RESULTS: Data from the investigation showed that a novel circRNA (circTADA2A, hsa_circ_0043278) was markedly downregulated in melanoma cells. Functionally, circTADA2A repressed cell proliferation, migration, invasion in melanoma cells. Mechanistically, circTADA2A interacted with CNBP, acting to suppress the binding of CNBP to the SLC38A1 promoter and subsequently restrained SLC38A1 transcription, which resulting in repression of melanoma progression. CONCLUSIONS: CircTADA2A suppresses melanoma progression by regulating CNBP/SLC38A1 axis, indicating a potential therapeutic target in melanoma.

The development of the neurocritical care specialty in China based on the analysis of neurocritical care unit volume and quality.

PURPOSE: Through three neurocritical care unit (NCCU) surveys in China, we tried to understand the development status of neurocritical care and clarify its future development. METHODS: Using a cross-sectional survey method and self-report questionnaires, the number and quality of NCCUs were investigated through three steps: administering the questionnaire, sorting the survey data, and analyzing the survey data. RESULTS: At the second and third surveys, the number of NCCUs (76/112/206) increased by 47% and 84%, respectively. The NCCUs were located in tertiary grade A hospitals or teaching hospitals (65/100/181) in most provinces (24/28/29). The numbers of full-time doctors (359/668/1337) and full-time nurses (904/1623/207) in the NCCUs increased, but the doctor-bed ratio and nurse-bed ratio were still insufficient (0.4:1 and 1.3:1). CONCLUSION: In the past 20 years, the growth rate of NCCUs in China has accelerated, while the allocation of medical staff has been insufficient. Although most NCCU hospital bed facilities and instruments and equipment tend to be adequate, there are obvious defects in some aspects of NCCUs.

EXPRESS: B-lymphocyte induced maturation protein-1 to inhibit inflammation and pyroptosis to alleviate sepsis injury.

Liver and lung tissue damage caused by sepsis still one of the causes of death. Blimp-1 has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. Animal and cell models were established by cecal ligation and puncture (CLP) method and LPS-induced RAW 264.7 cells respectively, and the role of Blimp-1 in regulation inflammatory response and pyroptosis was verified. The changes of inflammation and pyroptosis in liver and lung tissues of septic mice were determined by the addition of TAK-242 (TLR4 inhibitor). Cell pyroptosis and the level of inflammation was detected after Blimp-1 knockdown and TAK-242 treatment in the cell model. The expression of Blimp-1 was continuously increased in a septic mice model. After treatment with TAK-242, the expression of Blimp-1, pyroptosis and inflammatory levels were reduced in mice. In LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.

Treatment patterns and survival outcomes in patients with non-metastatic early-onset pancreatic cancer.

BACKGROUND: The incidence of patients with early-onset pancreatic cancer (EOPC; age ≤ 50 years at diagnosis) is on the rise, placing a heavy burden on individuals, families, and society. The role of combination therapy including surgery, radiotherapy, and chemotherapy in non-metastatic EOPC is not well-defined. AIM: To investigate the treatment patterns and survival outcomes in patients with non-metastatic EOPC. METHODS: A total of 277 patients with non-metastatic EOPC who were treated at our institution between 2017 and 2021 were investigated retrospectively. Overall survival (OS), disease-free survival, and progression-free survival were estimated using the Kaplan-Meier method. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors. RESULTS: With a median follow-up time of 34.6 months, the 1-year, 2-year, and 3-year OS rates for the entire cohort were 84.3%, 51.5%, and 27.6%, respectively. The median OS of patients with localized disease who received surgery alone and adjuvant therapy (AT) were 21.2 months and 28.8 months, respectively (P = 0.007). The median OS of patients with locally advanced disease who received radiotherapy-based combination therapy (RCT), surgery after neoadjuvant therapy (NAT), and chemotherapy were 28.5 months, 25.6 months, and 14.0 months, respectively (P = 0.002). The median OS after regional recurrence were 16.0 months, 13.4 months, and 8.9 months in the RCT, chemotherapy, and supportive therapy groups, respectively (P = 0.035). Multivariate analysis demonstrated that carbohydrate antigen 19-9 level, pathological grade, T-stage, N-stage, and resection were independent prognostic factors for non-metastatic EOPC. CONCLUSION: AT improves postoperative survival in localized patients. Surgery after NAT and RCT are the preferred therapeutic options for patients with locally advanced EOPC.

Long-term conservation tillage increase cotton rhizosphere sequestration of soil organic carbon by changing specific microbial CO2 fixation pathways in coastal saline soil.

Coastal saline soil is an important reserve resource for arable land globally. Data from 10 years of continuous stubble return and subsoiling experiments have revealed that these two conservation tillage measures significantly improve cotton rhizosphere soil organic carbon sequestration in coastal saline soil. However, the contribution of microbial fixation of atmospheric carbon dioxide (CO2) has remained unclear. Here, metagenomics and metabolomics analyses were used to deeply explore the microbial CO2 fixation process in rhizosphere soil of coastal saline cotton fields under long-term stubble return and subsoiling. Metagenomics analysis showed that stubble return and subsoiling mainly optimized CO2 fixing microorganism (CFM) communities by increasing the abundance of Acidobacteria, Gemmatimonadetes, and Chloroflexi, and improving composition diversity. Conjoint metagenomics and metabolomics analyses investigated the effects of stubble return and subsoiling on the reverse tricarboxylic acid (rTCA) cycle. The conversion of citrate to oxaloacetate was inhibited in the citrate cleavage reaction of the rTCA cycle. More citrate was converted to acetyl-CoA, which enhanced the subsequent CO2 fixation process of acetyl-CoA conversion to pyruvate. In the rTCA cycle reductive carboxylation reaction from 2-oxoglutarate to isocitrate, synthesis of the oxalosuccinate intermediate product was inhibited, with strengthened CO2 fixation involving the direct conversion of 2-oxoglutarate to isocitrate. The collective results demonstrate that stubble return and subsoiling optimizes rhizosphere CFM communities by increasing microbial diversity, in turn increasing CO2 fixation by enhancing the utilization of rTCA and 3-hydroxypropionate/4-hydroxybutyrate cycles by CFMs. These events increase the microbial CO2 fixation in the cotton rhizosphere, thereby promoting the accumulation of microbial biomass, and ultimately improving rhizosphere soil organic carbon. This study clarifies the impact of conservation tillage measures on microbial CO2 fixation in cotton rhizosphere of coastal saline soil, and provides fundamental data for the improvement of carbon sequestration in saline soil in agricultural ecosystems.

Portable ratiometric fluorescence detection of Cu2+and thiram.

Food contaminants pose a danger to human health, but rapid, sensitive and reliable food safety detection methods can offer a solution to this problem. In this study, an optical fiber ratiometric fluorescence sensing system based on carbon dots (CDs) and o-phenylenediamine (OPD) was constructed. The ratiometric fluorescence response of Cu2+and thiram was carried out by the fluorescence resonance energy transfer (FRET) between CDs and 2,3-diaminophenazine (ox-OPD, oxidized state o-phenylenediamine). The oxidation of OPD by Cu2+resulted in the formation of ox-OPD, which quenched the fluorescence of CDs and exhibited a new emission peak at 573 nm. The formation of a [dithiocarbamate-Cu2+] (DTC-Cu2+) complex by reacting thiram with Cu2+, inhibits the OPD oxidation reaction triggered by Cu2+, thus turning off the fluorescence signal of OPD-Cu2+. The as-established detection system presented excellent sensitivity and selectivity for the detection of Cu2+and thiram in the ranges of 1 ∼ 100µM and 5 ∼ 50µM, respectively. The lowest detection limits were 0.392µM for Cu2+and 0.522µM for thiram. Furthermore, actual sample analysis indicated that the sensor had the potential for Cu2+and thiram assays in real sample analysis.

Revelation of adhesive proteins affecting cellular contractility through reference-free traction force microscopy.

Over the past few decades, the critical role played by cellular contractility associated mechanotransduction in the regulation of cell functions has been revealed. In this case, numerous biomaterials have been chemically or structurally designed to manipulate cell behaviors through the regulation of cellular contractility. In particular, adhesive proteins including fibronectin, poly-L-lysine and collagen type I have been widely applied in various biomaterials to improve cell adhesion. Therefore, clarifying the effects of adhesive proteins on cellular contractility has been valuable for the development of biomaterial design. In this study, reference-free traction force microscopy with a well-organized microdot array was designed and prepared to investigate the relationship between adhesive proteins, cellular contractility, and mechanotransduction. The results showed that fibronectin and collagen type I were able to promote the assembly of focal adhesions and further enhance cellular contraction and YAP activity. In contrast, although poly-L-lysine supported cell spreading and elongation, it was inefficient at inducing cell contractility and activating YAP. Additionally, compared with cellular morphogenesis, cellular contraction was essential for YAP activation.

A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

The impact of gut microbiota on autoimmune thyroiditis and relationship with pregnancy outcomes: a review.

Autoimmune thyroiditis (AITD) is a T-cell-mediated, organ- specific autoimmune disease caused by interactions between genetic and environmental factors. Patients with AITD show thyroid lymphocyte infiltration and an increase in the titer of thyroid autoimmune antibodies, thereby altering the integrity of thyroid follicle epithelial cells and dysregulating their metabolism and immune function, leading to a decrease in multi-tissue metabolic activity. Research has shown that patients with AITD have a significantly higher risk of adverse pregnancy outcomes, such as infertility and miscarriage. Levothyroxine(LT4) treatment can improve the pregnancy outcomes of normal pregnant women with thyroid peroxidase antibodies(TPOAb) positivity, but it is not effective for invitro fertilization embryo transfer (IVF-ET) in women with normal thyroid function and positive TPOAb. Other factors may also influence pregnancy outcomes of patients with AITD. Recent studies have revealed that the gut microbiota participates in the occurrence and development of AITD by influencing the gut-thyroid axis. The bacterial abundance and diversity of patients with Hashimoto thyroiditis (HT) were significantly reduced, and the relative abundances of Bacteroides, fecal Bacillus, Prevotella, and Lactobacillus also decreased. The confirmation of whether adjusting the composition of the gut microbiota can improve pregnancy outcomes in patients with AITD is still pending. This article reviews the characteristics of the gut microbiota in patients with AITD and the current research on its impact in pregnancy.

Methylphenidate and Short-Term Cardiovascular Risk.

Importance: There are concerns about the safety of medications for treatment of attention-deficit/hyperactivity disorder (ADHD), with mixed evidence on possible cardiovascular risk. Objective: To assess whether short-term methylphenidate use is associated with risk of cardiovascular events. Design, Setting, and Participants: This retrospective, population-based cohort study was based on national Swedish registry data. Participants were individuals with ADHD aged 12 to 60 years with dispensed prescriptions of methylphenidate between January 1, 2007, and June 30, 2012. Each person receiving methylphenidate (n = 26 710) was matched on birth date, sex, and county to up to 10 nonusers without ADHD (n = 225 672). Statistical analyses were performed from September 13, 2022, to May 16, 2023. Main Outcomes and Measures: Rates of cardiovascular events, including ischemic heart disease, venous thromboembolism, heart failure, or tachyarrhythmias, 1 year before methylphenidate treatment and 6 months after treatment initiation were compared between individuals receiving methylphenidate and matched controls using a bayesian within-individual design. Analyses were stratified by history of cardiovascular events. Results: The cohort included 252 382 individuals (15 442 [57.8% men]; median age, 20 (IQR, 15-31) years). The overall incidence of cardiovascular events was 1.51 per 10 000 person-weeks (95% highest density interval [HDI], 1.35-1.69) for individuals receiving methylphenidate and 0.77 (95% HDI, 0.73-0.82) for the matched controls. Individuals treated with methylphenidate had an 87% posterior probability of having a higher rate of cardiovascular events after treatment initiation (incidence rate ratio [IRR], 1.41; 95% HDI, 1.09-1.88) compared with matched controls (IRR, 1.18; 95% HDI, 1.02-1.37). The posterior probabilities were 70% for at least a 10% increased risk of cardiovascular events in individuals receiving methylphenidate vs 49% in matched controls. No difference was found in this risk between individuals with and without a history of cardiovascular disease (IRR, 1.11; 95% HDI, 0.58-2.13). Conclusions and Relevance: In this cohort study, individuals receiving methylphenidate had a small increased cardiovascular risk vs matched controls in the 6 months after treatment initiation. However, there was little evidence for an increased risk of 20% or higher and for differences in risk increase between people with and without a history of cardiovascular disease. Therefore, before treatment initiation, careful consideration of the risk-benefit trade-off of methylphenidate would be useful, regardless of cardiovascular history.

Comparative effectiveness and safety of intermittent, repeated or continuous use of levosimendan, milrinone, or dobutamine in patients with advanced heart failure: a network and single-arm meta-analysis.

ABSTRACT: To synthesize the available evidence regarding differences in the long-term safety and efficacy of intermittent, repeated, or continuous palliative inotropic therapy among patients with advanced heart failure (HF). We systematically searched the PubMed, Embase, and Cochrane Library electronic databases, with a cutoff date of November 23, 2023, for studies reporting outcomes in adult patients with advanced HF treated with intermittent, repeated, or continuous levosimendan, milrinone, or dobutamine. Forty-one studies (18 randomized controlled trials and 23 cohort studies) comprising 5137 patients met the inclusion criteria. The results of the network meta-analysis of randomized controlled trials showed that levosimendan had significant advantages over milrinone or dobutamine in reducing mortality and improving LVEF. A single-arm meta-analysis also indicated that levosimendan had the lowest mortality and significantly improved BNP and LVEF. Regarding safety, hypotension events were observed more frequently in the levosimendan group and milrinone groups. However, the current evidence is limited by the heterogeneity and relatively small sample size of the studies.

Cervical Cancer Screening via Visual Inspection With Acetic Acid and Lugol Iodine for Triage of HPV-Positive Women.

Importance: Limited evidence supports the performance of human papillomavirus (HPV) DNA testing as a primary screening method, followed by triage with visual inspection with acetic acid, in areas with limited health care resources, as suggested by the 2021 World Health Organization guidelines. Objective: To evaluate the performance of visual inspection with acetic acid and Lugol iodine as a triage method for detecting cervical precancerous lesions among HPV-positive women in 1 visit. Design, Setting, and Participants: This cohort study examined the implementation of a government-led cervical cancer screening program conducted from January 1, 2016, to December 31, 2020, in Ordos City, China. Female residents, aged 35 to 64 years, who understood the screening procedures and voluntarily participated were included in the study. Women were excluded if they reported never having had sexual intercourse, were pregnant, had a hysterectomy, or had ever undergone treatment for cervical lesions. Statistical analysis was conducted from December 2022 to December 2023. Exposures: The program used the careHPV DNA assay as the primary screening method, and immediate triage was performed by visual inspection if HPV screening results were positive, with a 5-year screening interval. A colposcopy was performed for the women who had suspected cancer on visual inspection results or who were HPV positive and had abnormal visual inspection results, all in 1 visit. Main Outcomes and Measures: The rate of compliance with colposcopy and the detection rate of cervical intraepithelial neoplasia grade 2 or higher (CIN2+). Results: The study included 187 863 women (median age, 46 years [IQR, 40-52 years]) who participated in the program and had valid HPV test results. The overall prevalence of HPV positivity was 12.8% (24 070 of 187 863), and the adherence to triage with visual inspection among HPV-positive women was 93.9% (22 592 of 24 070). Among HPV-positive women, the rate of compliance with colposcopy was 65.6% (2714 of 4137), and the CIN2+ detection rate was 2.8% (643 of 22 592). Conclusions and Relevance: The findings of this cohort study suggest that the implementation of HPV testing, visual inspection, and colposcopy within 1 visit may mitigate losses to follow-up, detect precancerous lesions, and hold significant implications for screening in comparable areas with limited health care resources.