Diagnostic accuracy of automation and non-automation techniques for identifying Burkholderia pseudomallei: A systematic review and meta-analysis.

BACKGROUND: Burkholderia pseudomallei, a Gram-negative pathogen, causes melioidosis. Although various clinical laboratory identification methods exist, culture-based techniques lack comprehensive evaluation. Thus, this systematic review and meta-analysis aimed to assess the diagnostic accuracy of culture-based automation and non-automation methods. METHODS: Data were collected via PubMed/MEDLINE, EMBASE, and Scopus using specific search strategies. Selected studies underwent bias assessment using QUADAS-2. Sensitivity and specificity were computed, generating pooled estimates. Heterogeneity was assessed using I2 statistics. RESULTS: The review encompassed 20 studies with 2988 B. pseudomallei samples and 753 non-B. pseudomallei samples. Automation-based methods, particularly with updating databases, exhibited high pooled sensitivity (82.79%; 95% CI 64.44-95.85%) and specificity (99.94%; 95% CI 98.93-100.00%). Subgroup analysis highlighted superior sensitivity for updating-database automation (96.42%, 95% CI 90.01-99.87%) compared to non-updating (3.31%, 95% CI 0.00-10.28%), while specificity remained high at 99.94% (95% CI 98.93-100%). Non-automation methods displayed varying sensitivity and specificity. In-house latex agglutination demonstrated the highest sensitivity (100%; 95% CI 98.49-100%), followed by commercial latex agglutination (99.24%; 95% CI 96.64-100%). However, API 20E had the lowest sensitivity (19.42%; 95% CI 12.94-28.10%). Overall, non-automation tools showed sensitivity of 88.34% (95% CI 77.30-96.25%) and specificity of 90.76% (95% CI 78.45-98.57%). CONCLUSION: The study underscores automation's crucial role in accurately identifying B. pseudomallei, supporting evidence-based melioidosis management decisions. Automation technologies, especially those with updating databases, provide reliable and efficient identification.

Effect modification of diabetic status on the association between exposure to particulate matter and cardiac arrhythmias in a general population: A systematic review and meta-analysis.

Particulate matter (PM) has various health effects, including cardiovascular diseases. Exposure to PM and a diagnosis of diabetes mellitus (DM) have been associated with an increased risk of cardiac arrhythmias. However, no comprehensive synthesis has been conducted to examine the modifying effect of DM on the association between PM and arrhythmia events. Thus, the objectives of this review were to investigate whether the association of PM is linked to cardiac arrhythmias and whether DM status modifies its effect in the general population. The search was conducted on PubMed/MEDLINE and Embase until January 18, 2023. We included cohort and case-crossover studies reporting the effect of PM exposure on cardiac arrhythmias and examining the role of diabetes as an effect modifier. We used the DerSimonian and Laird random-effects model to calculate the pooled estimates. A total of 217 studies were found and subsequently screened. Nine studies met the inclusion criteria, and five of them were included in the meta-analysis. The participants numbered 4,431,452, with 2,556 having DM. Exposure to PM of any size showed a significant effect on arrhythmias in the overall population (OR 1.10, 95% CI 1.04-1.16). However, the effect modification of DM was not significant (OR 1.18 (95% CI 1.01-1.38) for DM; OR 1.08 (95% CI 1.02-1.14) for non-DM; p-value of subgroup difference = 0.304). Exposure to higher PM concentrations significantly increases cardiac arrhythmias requiring hospital or emergency visits. Although the impact on diabetic individuals is not significant, diabetic patients should still be considered at risk. Further studies with larger sample sizes and low bias are needed.

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.

Development of a clinical prediction tool for extubation failure in pediatric cardiac intensive care unit.

Introduction/objective: Extubation failure in pediatric patients with congenital or acquired heart diseases increases morbidity and mortality. This study aimed to develop a clinical risk score for predicting extubation failure to guide proper clinical decision-making and management. Methods: We conducted a retrospective study. This clinical prediction score was developed using data from the Pediatric Cardiac Intensive Care Unit (PCICU) of the Faculty of Medicine, Chiang Mai University, Thailand, from July 2016 to May 2022. Extubation failure was defined as the requirement for re-intubation within 48 h after extubation. Multivariable logistic regression was used for modeling. The score was evaluated in terms of discrimination and calibration. Results: A total of 352 extubation events from 270 patients were documented. Among these, 40 events (11.36%) were extubation failure. Factors associated with extubation failure included history of pneumonia (OR: 4.14, 95% CI: 1.83-9.37, p = 0.001), history of re-intubation (OR: 5.99, 95% CI: 2.12-16.98, p = 0.001), and high saturation in physiologic cyanosis (OR: 5.94, 95% CI: 1.87-18.84, p = 0.003). These three factors were utilized to develop the risk score. The score showed acceptable discrimination with an area under the curve (AUC) of 0.77 (95% CI: 0.69-0.86), and good calibration. Conclusion: The derived Pediatric CMU Extubation Failure Prediction Score (Ped-CMU ExFPS) could satisfactorily predict extubation failure in pediatric cardiac patients. Employing this score could promote proper personalized care. We suggest conducting further external validation studies before considering implementation in practice.

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.

Coronary artery calcium (CAC) score for cardiovascular risk stratification in a Thai clinical cohort: A comparison of absolute scores and age-sex-specific percentiles.

Purposes: Coronary artery calcium (CAC) score provides a quantification of atherosclerotic plaque within the coronary arteries. This study aimed to examine the prevalence and CAC score distribution and to evaluate the association of each CAC score classifications with major adverse cardiovascular events (MACE) in a Thai clinical cohort. Methods: This study was a retrospective observational cohort. We included patients aged above 35 years who underwent CAC score testing. The absolute and age-sex specific percentile classifications were categorized as 0, 1 to 10, 11 to 100, 101 to 400, and >400 and 0, <75th, 75th - 90th, and >90th, respectively. The endpoint was MACE, including cardiovascular death, myocardial infarction, heart failure hospitalization, coronary artery revascularization procedure, and stroke. Multivariable Cox regression was used to estimate the hazard ratios. The discriminative performance between classifications were compared using Harrell's C-statistics. The agreement was assessed via Cohen's Kappa. Results: This study included 440 patients, with approximately 70% of Thai patients exhibiting a CAC score. CAC score distributed higher in male than female and increased with age. Both CAC score classification demonstrated the acceptable predictive performance. However, fair agreement was observed between classifications (Cohen's kappa 0.51, 95%CI 0.42-0.59). Within the absolute classification, a higher CAC score was associated with increased hazard ratios for MACE across stratified age-sex-specific percentile levels. In contrast, the hazard ratios for MACE did not consistently rise with higher age-sex-specific percentile CAC score when stratified by absolute CAC score levels. Conclusions: Both absolute and age-sex-specific percentile CAC score demonstrated acceptable performance in predicting MACE. However, the absolute CAC score classification may be more suitable for risk stratification within the Thai clinical cohort. Our findings offer supportive information that could inform future recommendations for CAC score testing criteria within national clinical practice guidelines.

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.

The efficacy of prophylactic metoclopramide in preventing nausea and vomiting in patients with acute pain treated with intravenous tramadol: a randomized double-blinded, placebo-controlled trial.

OBJECTIVE: To examine the clinical efficacy of prophylactic metoclopramide in reducing the incidence of nausea and vomiting in emergency department (ED) patients with acute pain who were treated with intravenous tramadol. RESULTS: We conducted a single-center randomized, double-blinded, placebo-controlled trial. A total of 99 ED patients presented with acute pain were recruited. Sixty-four patients were randomized, 31 patients in the treatment arm and 33 in the control arm. Overall, there were no significant differences in baseline characteristics between treatment arm and control arm. Only one patient within each arm reported having nausea symptom. No patients reported vomiting episode. There was no statistically significant difference in the proportion of patients with nausea or vomiting symptoms between the two groups (3.2% in the treatment arm vs. 3.0% in the control arm, p = 1.000). The administration of prophylactic metoclopramide may not provide additional benefit in reducing the occurrence of nausea and/or vomiting episode in ED patients with acute pain treated with intravenous tramadol. Trial registration Randomized clinical trial TCTR20220525001; registration date: 21 October 2021. Retrospectively registered.

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.

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.

House dust mite allergen immunotherapy for monosensitized versus polysensitized patients with allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: Most patients with allergic rhinitis are polysensitized. The efficacy of house dust mite (HDM) allergen immunotherapy (AIT) compared between monosensitized and polysensitized patients remains limited. OBJECTIVE: To systematically review the efficacy and safety of HDM AIT compared between monosensitized and polysensitized patients with allergic rhinitis. METHODS: We searched PubMed/MEDLINE, Scopus, EMBASE, and the Cochrane central register of Controlled Trials (CENTRAL) until June 2022. The primary outcome was the changes from baseline in total nasal symptom score (TNSS). Secondary outcomes were changes from baseline in total medication score (TMS), combined symptom medication score (CSMS), visual analog scale (VAS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, immunological parameters, and adverse events (AEs). RESULTS: Of 13 eligible studies, 10 prospective cohorts, 2 retrospective cohorts, and 1 matched cohort, we identified 10 studies for quantitative synthesis. There were 1,113 patients with allergic rhinitis, 566 with HDM monosensitization and 547 with polysensitization to HDM and other allergens. There was no significant difference in the pooled mean changes of the 2 groups in TNSS (SMD -0.05, 95%CI: -0.22 to 0.11, p = 0.532) and VAS (SMD -0.20, 95%CI: -0.42 to 0.01, p = 0.060) with moderate certainty of evidence. The changes in TMS, CSMS, and RQLQ were similar between the 2 groups with very low certainty of evidence. The AEs were mild and comparable between the 2 groups. The immunological indices remained inconsistent and were not predictive of clinical responses. CONCLUSIONS: A single HDM AIT similarly improved clinical outcomes in monosensitized and polysensitized patients with allergic rhinitis.

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.

High alert drugs screening using gradient boosting classifier.

Prescription errors in high alert drugs (HAD), a group of drugs that have a high risk of complications and potential negative consequences, are a major and serious problem in medicine. Standardized hospital interventions, protocols, or guidelines were implemented to reduce the errors but were not found to be highly effective. Machine learning driven clinical decision support systems (CDSS) show a potential solution to address this problem. We developed a HAD screening protocol with a machine learning model using Gradient Boosting Classifier and screening parameters to identify the events of HAD prescription errors from the drug prescriptions of out and inpatients at Maharaj Nakhon Chiang Mai hospital in 2018. The machine learning algorithm was able to screen drug prescription events with a risk of HAD inappropriate use and identify over 98% of actual HAD mismatches in the test set and 99% in the evaluation set. This study demonstrates that machine learning plays an important role and has potential benefit to screen and reduce errors in HAD prescriptions.