Optimal volume for the draw-and-return methods to enhance activated partial thromboplastin time ratio accuracy in hemodialysis patients with central venous catheters.

Background: Significant errors of activated partial thromboplastin time (aPTT) ratio were frequently observed in blood sampling from central venous dialysis catheter (CVC) of hemodialysis (HD) patients. Following the draw-and-return methods, initial blood withdrawal from the catheter before sampling can reduce the error, but the optimal withdrawal volume remains undetermined. Aim: The objective of this study is to determine the optimal blood withdrawal volume for the draw-and-return methods to improve aPTT ratio accuracy in hemodialysis patients with CVC. Methods: A prospective study was conducted in patients receiving HD via CVC. Four blood samples were collected from each patient, involving a peripheral venipuncture and three draw-and-return samples (10 ml, 20 ml and 25 ml groups). The aPTT ratio of a peripheral sample was used as a reference to determine the aPTT ratio accuracy for each draw-and-return group. Subsequently, the agreement was illustrated using modified Bland-Altman plot. Results: A total of 1,000 samples were obtained from 250 patients. The patients had a mean age of 59.6 ± 15.4 years, with 17.2% using citrate as the CVC's locking agent. The adjusted accuracies of the aPTT ratio varied significantly among the three withdrawal volumes (p-value <0.001). The 25 ml group demonstrated the highest accuracy (43.2%; 95%CI, 38.0-48.4), followed by the 20 ml group (30.0%; 95%CI, 24.9-35.2), and the 10 ml group (18.0%; 95%CI, 12.8-23.2). Additionally, using citrate as a locking agent provided more than 80.0% aPTT ratio accuracy, whereas heparin demonstrated inferior accuracy even in the 25 ml withdrawal group. Conclusion: The optimal blood withdraw volume for the draw-and-return methods concluded at 20 ml for citrate locked-CVC and 25 ml for heparin which significantly improved aPTT ratio accuracies. Applying citrate as a locking agent provides clear benefits for aPTT ratio monitoring, while peripheral venipuncture is recommended in cases of heparin-locked CVC.

Diagnostic scoring systems for tuberculous pleural effusion in patients with lymphocyte-predominant exudative pleural profile: A development study.

Background: Diagnosing tuberculous pleural effusion (TPE) in patients presenting with Lymphocyte-Predominant Exudative pleural effusion (LPE) is challenging, due to the poor clinical utility of TB culture. Adenosine deaminase (ADA) has been recommended for diagnosis, but its high cost and limited availability hinder its clinical utility. We aim to develop diagnostic prediction tools for Thai patients with LPE in scenarios where pleural fluid ADA is available but yields negative results and in situations where pleural fluid ADA is not available. Methods: Two diagnostic prediction tools were developed using retrospective data from patients with LPE at Surin Hospital. Model 1 is for ADA-negative results, and Model 2 is for situations where pleural fluid ADA testing is unavailable. The models were derived using multivariable logistic regression and presented as two clinical scoring systems: round-up and count scoring. The score cut-point that achieves a positive predictive value (PPV) comparable to the post-test probability of a pleural fluid ADA at a cut-point of 40 U/L was used as a threshold for initiating anti-TB treatment. Results: A total of 359 patients were eligible for analysis, with 166 diagnosed with TPE and 193 diagnosed with non-TPE. Age <40 years, fever, pleural fluid protein ≥5 g/dL, male gender, pleural fluid color, and pleural fluid ADA ≥20 U/L were identified as final predictors. Both models demonstrated excellent discriminative ability (AuROC: 0.85 to 0.89). The round-up scoring demonstrated PPV above 90% at cut-off points of 4 and 4.5, while the count scoring achieved cut-off points of 3 and 4 for Model 1 (Lex-2P2A) and Model 2 (Lex-2P-MAC), respectively. Conclusion: These diagnostic tools offer valuable assistance in differentiating between TPE and non-TPE in LPE patients with negative pleural fluid ADA (Lex-2P2A) and in settings where pleural fluid ADA testing is not available (Lex-2P-MAC). Implementing these diagnostic scores may have the potential to improve TPE diagnosis and facilitate prompt initiation of treatment.

Combinatorial Gene Expression Profiling of Serum HULC, HOTAIR, and UCA1 lncRNAs to Differentiate Hepatocellular Carcinoma from Liver Diseases: A Systematic Review and Meta-Analysis.

Hepatocellular carcinoma (HCC) presents a significant global health challenge due to limited early detection methods, primarily relying on conventional approaches like imaging and alpha-fetoprotein (AFP). Although non-coding RNAs (ncRNAs) show promise as potential biomarkers in HCC, their true utility remains uncertain. We conducted a comprehensive review of 76 articles, analyzing 88 circulating lncRNAs in 6426 HCC patients. However, the lack of a standardized workflow protocol has hampered holistic comparisons across the literature. Consequently, we herein confined our meta-analysis to only a subset of these lncRNAs. The combined analysis of serum highly upregulated in liver cancer (HULC) gene expression with homeobox transcript antisense intergenic RNA (HOTAIR) and urothelial carcinoma-associated 1 (UCA1) demonstrated markedly enhanced sensitivity and specificity in diagnostic capability compared to traditional biomarkers or other ncRNAs. These findings could have substantial implications for the early diagnosis and tailored treatment of HCC.

Genetic association of beta-lactams-induced hypersensitivity reactions: A systematic review of genome-wide evidence and meta-analysis of candidate genes.

Importance: Beta-lactams (BLs) are the most prescribed antibiotics, being the most frequent cause of drug allergy. However, the association between BL allergy and genetic variations is still unclear. Objective: This systematic review and meta-analysis aimed to summarize the genetic effects of BL-induced hypersensitivity using existing evidence. Methods: We searched PubMed, Medline, Scopus, EMBASE, CINAHL, and Cochrane Library from inception to September 15, 2022 with no language restriction. Genetic association studies investigating genetic variant/polymorphism and risk of drug-induced hypersensitivity reactions among individuals receiving BL-antibiotics were included. We excluded studies of acute interstitial nephritis, drug-induced liver injury, serum sickness, and isolated drug fever. Data were comprehensively synthesized and quality of study were assessed using STrengthening the Reporting of Genetic Association Studies (STREGA). The record screening, extraction and quality assessment were performed by two reviewers and discussions were made to resolve discrepancies. The effects of each variant were pooled and evaluated by modified Venice criteria. Results: A total of 9276 records were identified, and 31 studies were eligible for inclusion. Twenty-seven were candidate-gene association studies (5416 cases and 5939 controls), while the others were next-generation sequencing (NGS) or genome-wide association studies (GWASs) (119 838 cases and 1 487 111 controls). Forty-nine polymorphisms were identified and most of them located in allergic reaction pathways. Meta-analyses of 15 candidate variants in a mixture of both immediate and non-immediate reactions revealed weak genetic effects of rs1801275 (8 studies; n = 1,560; odd ratio 0.73; 95%CI: 0.57-0.93) and rs20541 (4 studies; n = 1,482; odd ratio 1.34; 95%CI: 1.07-1.68) in IL4R and IL13, respectively. Results from GWASs and NGS identified, and confirmed associations in HLA regions including HLA-DRA, HLA-B, HLA-DQA, HLA-DRB1, and HLA-DRB3. Conclusion: Our study summarized genetic evidence influencing BL-induced hypersensitivity and estimated effects of potential variants. We postulated that the genomic studies provide better insights to the mechanism of reactions and suggest potential effects of HLA Class II variants. However, results were inconsistent and unable to generalize in different settings. Further high-throughput studies with a well-defined function, epigenetic interaction, incorporated with clinical factors, would be beneficial for risk identification in BL-induced hypersensitivity.

Performance of the Dutch clinical prediction rule for the ambulation outcome after spinal cord injury in a middle-income country clinical setting: an external validation study in the Thai retrospective cohort.

OBJECTIVE: To perform external geographic and domain validation of the clinical prediction rule (CPR) of the ambulation outcome of patients with traumatic spinal cord injury (SCI) originally developed by van Middendorp, et al. (2011) in Thais with traumatic and non-traumatic SCI. STUDY DESIGN: Retrospective cohort study. SETTING: A tertiary rehabilitation facility in Chiang Mai, Thailand. METHODS: A validation data set, including predictive (age and four neurological variables) and outcome (ambulation status) parameters was retrospectively collected from medical records of patients with traumatic and non-traumatic SCI admitted between December 2007 and December 2019. The performance of the original model was evaluated in both discrimination and calibration aspects, using an area under the receiver-operating characteristic curve (auROC) and calibration curves, respectively. RESULTS: Three hundred and thirty-three patients with SCI were included in the validation set. The prevalence of ambulators was 59% (197 of 333 participants). An auROC of 0.93 (95% CI 0.90-0.96) indicated excellent discrimination whereas the calibration curve demonstrated underestimation, especially in patients with AIS grade D. Performance of the CPR was decreased but acceptable in patients with non-traumatic SCI. CONCLUSIONS: Our external validation study demonstrated excellent discrimination but slightly underestimated calibration of the CPR of ambulation outcome after SCI. Regardless of the geographic and etiologic background of the population, the Dutch CPR could be applied to predict the ambulation outcome in patients with SCI.

Validation of a Diagnostic Model to Differentiate Multiple Myeloma from Bone Metastasis.

Purpose: A diagnostic model to differentiate multiple myeloma (MM) from bone metastasis (BM) in patients with destructive bone lesions (MM-BM DDx) was developed to promote timely and appropriate referral of patients with MM to hematologists. External validation has never been conducted. This study aims to externally validate the performance of the MM-BM DDx model. Patients and Methods: This multi-center external validation study was conducted using retrospective data of patients over 45 years old diagnosed with MM or BM at six university-affiliated hospitals in Thailand from 2016 to 2022. The MM-BM DDx development dataset, including patients from 2012 to 2015, was utilized during external validation. Diagnostic indicators for MM included in the MM-BM DDx model are serum creatinine, serum globulin, and serum alkaline phosphatase (ALP). MM and BM diagnosis was based on the documented International Classification of Diseases 10th Revision codes. Model performance was evaluated in terms of discrimination, calibration, and accuracy. Results: A total of 3018 patients were included in the validation dataset (586 with MM and 2432 with BM). Clinical characteristics were similar between the validation and development datasets. The MM-BM DDx model's predictions showed an AUC of 0.89 (95% CI, 0.87, 0.90). The predicted probabilities of MM from the model increased concordantly with the observed proportion of MM within the validation dataset. The estimated sensitivity, specificity, and LR for each odds class in the validation dataset were similar to those of the development dataset. Conclusion: The discriminative ability and calibration of the MM-BM DDx model were found to be preserved during external validation. These findings provide support for the practical use of the MM-BM DDx model to assist clinicians in identifying patients with destructive bone lesions who are likely to have MM and enable them to arrange timely referrals for further evaluation by hematologists.

Performance of the Matsumiya scoring system in cervical cancer patients with bone metastasis: an external validation study.

BACKGROUND: Accurate prognostic prediction of survival in cervical cancer patients with bone metastasis is important for treatment planning. We aimed to externally validate the Matsumiya scoring system using external patient data. METHODS: We collected a retrospective cohort of patients with cervical cancer diagnosed with bone metastasis at Chiang Mai University Hospital from 1st January 2007 to 31st December 2016. The Matsumiya score was composed of 5 predictors, including the presence of extraskeletal metastasis, ECOG performance status, history of previous chemo- or radiotherapy, the presence of multiple bone metastasis, and bone metastasis-free interval < 12 months. Harrell's C-statistics and score calibration plots were used to evaluate the score performance. We also reconstructed the development study to estimate apparent performance values for comparison during external validation. RESULTS: A total of 124 cervical cancer patients with bone metastasis were included in this study. The 13-, 26-, and 52-week survival probabilities in the validation study were 70.1%, 50.5%, and 25.7%, respectively. Several differences were identified between development and validation studies regarding clinical characteristics, case-mix, and predictor-outcome associations. Harrell's C-statistics in the development and validation study were 0.714 and 0.567. The score showed poor agreement between the observed and the predicted survival probabilities in the validation study. Score reweighting and refitting showed only modest improvement in performance. CONCLUSION: A prognostic scoring system by Matsumiya et al. performed poorly in our cohort of Thai cervical cancer patients with bone metastasis. We suggested that the score should be sufficiently updated before being used.

Genetic Association of Beta-Lactams-Induced Hypersensitivity Reactions: A Protocol for Systematic Review and Meta-Analysis.

Beta-lactam (BL) antibiotics are among the drugs commonly related to hypersensitivity reactions. Several candidate gene studies and genome-wide association studies have reported associations of genetic variants and hypersensitivity reactions induced by BL antibiotics. However, the results were inconclusive. This protocol details a comprehensive systematic review of genetic factors associated with BL-induced hypersensitivity. A systematic search of literature related to genetic associations of BL-induced hypersensitivity will be performed through PubMed, Medline, Scopus, EMBASE, Web of Science, CINAHL, and the Cochrane central register of Controlled Trials (CENTRAL) from their inception dates with no language restrictions. Two reviewers will independently screen, extract, and appraise the risk of bias. Frequencies of genetic variants that comply with Hardy-Weinberg equilibrium will be extracted and pooled. Genetic models will be applied to variant effect calculation as per allele and genotype analysis. Based on statistical heterogeneity among studies, common effect estimation (odds ratio) and its corresponding 95% confidence interval will be analyzed. Sensitivity and subgroup analyses will be performed to determine the robustness of eligible studies. This systematic review and meta-analysis will provide comprehensive evidence of genetic effects regarding BL-induced hypersensitivity. The findings will enlighten the determination of disease-related genotypes that would potentially reveal allergy profiling in patients.

Development of a Clinical Risk Score for Prediction of Life-Threatening Arrhythmia Events in Patients with ST Elevated Acute Coronary Syndrome after Primary Percutaneous Coronary Intervention.

ST-elevated acute coronary syndrome (STEACS) is a serious condition requiring timely treatment. Reperfusion with primary percutaneous coronary intervention (pPCI) is recommended and preferred over fibrinolysis. Despite its efficacy, lethal complications, such as life-threatening arrhythmia (LTA), are common in post-PCI patients. Although various risk assessment tools were developed, only a few focus on LTA prediction. This study aimed to develop a risk score to predict LTA events after pPCI. A risk score was developed using a retrospective cohort of consecutive patients with STEACS who underwent pPCI at Chiangrai Prachanukroh Hospital from January 2012 to December 2016. LTA is defined as the occurrence of malignant arrhythmia that requires advanced cardiovascular life support (ACLS) within 72 h after pPCI. Logistic regression was used for model derivation. Among 273 patients, 43 (15.8%) developed LTA events. Seven independent predictors were identified: female sex, hemoglobin < 12 gm/dL, pre- and intra-procedural events (i.e., respiratory failure and pulseless arrest), IABP insertion, intervention duration > 60 min, and desaturation after pPCI. The LTA score showed an AuROC of 0.93 (95%CI 0.90, 0.97). The score was categorized into three risk categories: low (<2.5), moderate (2.5-4), and high risk (>4) for LTA events. The LTA score demonstrated high predictive performance and potential clinical utility for predicting LTA events after pPCI.

Efficacy and Safety of House Dust Mite Sublingual Immunotherapy Tablet in Allergic Asthma: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: House dust mite sublingual immunotherapy (HDM SLIT) effectively treats allergic rhinitis (AR). However, the evidence of HDM SLIT for allergic asthma remained limited. OBJECTIVE: To systematically review the efficacy and safety of HDM SLIT tablets in patients with allergic asthma. METHODS: We performed a systematic search through PubMed, Scopus, EMBASE, Web of Science, the Cochrane Center of Controlled Trials, and Google Scholar for randomized controlled trials (RCTs) that addressed the efficacy and safety of HDM SLIT tablets compared with placebo or no intervention in allergic asthma from their inception date until September 2021. The primary outcome was the reduction in inhaled corticosteroids (ICS) dose. Additional outcomes were asthma control, exacerbation, lung function, quality-of-life, and adverse events. RESULTS: There were 7 RCTs, 5 studies in allergic asthma (4 in adults and 1 in children), and 2 in AR with or without asthma. The 6 standardized quality (SQ) HDM effectively reduced ICS dose in well- to partly controlled mild-to-moderate asthma in 1 RCT. Two RCTs evaluated the efficacy of 6 SQ and 12 SQ HDM in reducing asthma exacerbation in partly controlled moderate-to-severe asthma, and their results were inconsistent. One study in children with mild-to-moderate asthma found no benefit of HDM SLIT. Two RCTs in AR with or without mild-to-moderate asthma showed improvement of asthma symptoms. Adverse events were primarily local, and anaphylaxis treated with epinephrine was reported in 3 patients. CONCLUSIONS: The HDM SLIT tablets tend to effectively reduce ICS use in adults and adolescents with well- to partly controlled mild-to-moderate allergic asthma with a favorable safety profile.

Pharmacological interventions for hidradenitis suppurativa: a protocol for systematic review and network meta-analysis of randomised trials and non-randomised studies.

INTRODUCTION: Therapeutic recommendations for hidradenitis suppurativa (HS) have recently shifted towards non-invasive pharmacological options. Recent evidence has shown promising efficacy for specific treatments. However, data regarding the comparative efficacy of these treatments in patients with HS are still limited. Therefore, we plan to conduct a systematic review and network meta-analysis (NMA) to summarise the benefits and harms of different pharmacological interventions for treating people living with HS. METHODS AND ANALYSIS: We will search electronic databases, including Medline, Embase, PubMed, Web of Science, Scopus, CINAHL and Cochrane Library beginning from their inception dates with no language restrictions. A grey literature search will be performed to supplement the electronic databases. Both randomised trials and non-randomised studies using validated measurement tools that investigated the benefits and harms of pharmacological interventions among people living with HS will be included. The predefined primary outcomes will include treatment responses that reflect the patient's perspective and all-cause discontinuation. Screening, selection, extraction, assessment of the risk of bias and analysis of the strength of the evidence will be performed independently by a pair of reviewers. A two-step approach of traditional pairwise and NMA will be performed. Based on a random-effects model, standardised weighted mean differences and ORs with corresponding 95% CIs will be pooled as effect estimates for the continuous and categorical endpoints, respectively. Statistical and methodological heterogeneities will be assessed. Preplanned subgroup analyses and univariate meta-regression will be conducted to quantify the potential sources of heterogeneity. Evidence-based synthesis will be based on the magnitudes of effect size, evidence certainty and the surface under the cumulative ranking curve values. ETHICS AND DISSEMINATION: Ethical approval is not required because this study is based on existing published data. These findings will be disseminated through scientific meetings and publications in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42022302795.

Unraveling Haplotype Diversity of the Apical Membrane Antigen-1 Gene in Plasmodium falciparum Populations in Thailand.

Development of an effective vaccine is critically needed for the prevention of malaria. One of the key antigens for malaria vaccines is the apical membrane antigen 1 (AMA-1) of the human malaria parasite Plasmodium falciparum, the surface protein for erythrocyte invasion of the parasite. The gene encoding AMA-1 has been sequenced from populations of P. falciparum worldwide, but the haplotype diversity of the gene in P. falciparum populations in the Greater Mekong Subregion (GMS), including Thailand, remains to be characterized. In the present study, the AMA-1 gene was PCR amplified and sequenced from the genomic DNA of 65 P. falciparum isolates from 5 endemic areas in Thailand. The nearly full-length 1,848 nucleotide sequence of AMA-1 was subjected to molecular analyses, including nucleotide sequence diversity, haplotype diversity and deduced amino acid sequence diversity and neutrality tests. Phylogenetic analysis and pairwise population differentiation (Fst indices) were performed to infer the population structure. The analyses identified 60 single nucleotide polymorphic loci, predominately located in domain I of AMA-1. A total of 31 unique AMA-1 haplotypes were identified, which included 11 novel ones. The phylogenetic tree of the AMA-1 haplotypes revealed multiple clades of AMA-1, each of which contained parasites of multiple geographical origins, consistent with the Fst indices indicating genetic homogeneity or gene flow among geographically distinct populations of P. falciparum in Thailand's borders with Myanmar, Laos and Cambodia. In summary, the study revealed novel haplotypes and population structure needed for the further advancement of AMA-1-based malaria vaccines in the GMS.