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Fulltext A clinical tool to predict Plasmodium vivax recurrence in Malaysia

Mat Ariffin N, Islahudin F, Kumolosasi E, Makmor-Bakry M

BMC Infect Dis, 2017 12 08;17(1):759.
PMID: 29216842 DOI: 10.1186/s12879-017-2868-9

BACKGROUND: Recurrence rates of Plasmodium vivax infections differ across various geographic regions. Interestingly, South-East Asia and the Asia-Pacific region are documented to exhibit the most frequent recurrence incidences. Identifying patients at a higher risk for recurrences gives valuable information in strengthening the efforts to control P. vivax infections. The aim of the study was to develop a tool to identify P. vivax- infected patients that are at a higher risk of recurrence in Malaysia.
METHODS: Patient data was obtained retrospectively through the Ministry of Health, Malaysia, from 2011 to 2016. Patients with incomplete data were excluded. A total of 2044 clinical P. vivax malaria cases treated with primaquine were included. Data collected were patient, disease, and treatment characteristics. Two-thirds of the cases (n = 1362) were used to develop a clinical risk score, while the remaining third (n = 682) was used for validation.
RESULTS: Using multivariate analysis, age (p = 0.03), gametocyte sexual count (p = 0.04), indigenous transmission (p = 0.04), type of treatment (p = 0.12), and incomplete primaquine treatment (p = 0.14) were found to be predictors of recurrence after controlling for other confounding factors; these predictors were then used in developing the final model. The beta-coefficient values were used to develop a clinical scoring tool to predict possible recurrence. The total scores ranged between 0 and 8. A higher score indicated a higher risk for recurrence (odds ratio [OR]: 1.971; 95% confidence interval [CI]: 1.562-2.487; p ≤ 0.001). The area under the receiver operating characteristic (ROC) curve of the developed (n = 1362) and validated model (n = 682) was of good accuracy (ROC: 0.728, 95% CI: 0.670-0.785, p value ROC: 0.766, 95% CI: 0.700-0.833, p-value ROC curves showed no significant difference in predicting recurrence based on the constructed scoring mechanism (p = 0.399; Z-value: -0.8441; standard error: 0.045).
CONCLUSIONS: The developed model to predict recurrence was found to be of good accuracy and could be a useful tool in targeting patients at a higher risk for recurrence for closer monitoring during follow-up, after treatment with primaquine.

Matched MeSH terms: ROC Curve
Fulltext A novel and non-invasive approach utilising nasal washings for the detection of nasopharyngeal carcinoma

Tan GW, Sivanesan VM, Abdul Rahman FI, Hassan F, Hasbullah HH, Ng CC, et al.

Int J Cancer, 2019 Oct 15;145(8):2260-2266.
PMID: 30698824 DOI: 10.1002/ijc.32173

Nasopharyngeal carcinoma (NPC) is an epithelial cancer of the nasopharynx which is highly associated with Epstein-Barr virus (EBV). Worldwide, most of the top 20 countries with the highest incidence and mortality rates of NPC are low- and middle-income countries. Many studies had demonstrated that EBV could be detected in the tissue, serum and plasma of NPC patients. In this study, we explored the potential of assays based on non-invasive nasal washings (NW) as a diagnostic and prognostic tool for NPC. A total of 128 patients were evaluated for NW EBV DNA loads and a subset of these samples were also tested for 27 EBV and human miRNAs shortlisted from literature. EBV DNA and seven miRNAs showed area under the receiver operating characteristic curve (AUC) values of more than 0.7, suggestive of their potential utility to detect NPC. Logistic regression analyses suggested that combination of two NW assays that test for EBNA-1 and hsa-miR-21 had the best performance in detecting NPC. The trend of NW EBV DNA load matched with clinical outcome of 71.4% (10 out of 14) NPC patients being followed-up. In summary, the non-invasive NW testing panel may be particularly useful for NPC screening in remote areas where healthcare facilities and otolaryngologists are lacking, and may encourage frequent testing of individuals in the high risk groups who are reluctant to have their blood tested. However, further validation in an independent cohort is required to strengthen the utility of this testing panel as a non-invasive detection tool for NPC.

Matched MeSH terms: ROC Curve
Fulltext A metabolomic analysis of thiol response for standard and modified N-acetyl cysteine treatment regimens in patients with acetaminophen overdose

Dear JW, Ng ML, Bateman DN, Leroy Sivappiragasam P, Choi H, Khoo BBJ, et al.

Clin Transl Sci, 2021 Jul;14(4):1476-1489.
PMID: 33742775 DOI: 10.1111/cts.13009

N-acetylcysteine (NAC) is an antidote to prevent acetaminophen (paracetamol-APAP)-induced acute liver injury (ALI). The 3-bag licensed 20.25 h standard regimen, and a 12 h modified regimen, are used to treat APAP overdose. This study evaluated the redox thiol response and APAP metabolites, in patients with a single APAP overdose treated with either the 20.25 h standard or 12 h modified regimen. We used liquid chromatography tandem mass spectrometry to quantify clinically important oxidative stress biomarkers and APAP metabolites in plasma samples from 45 patients who participated in a randomized controlled trial (SNAP trial). We investigated the time course response of plasma metabolites at predose, 12 h, and 20.25 h post-start of NAC infusion. The results showed that the 12 h modified regimen resulted in a significant elevation of plasma NAC and cysteine concentrations at 12 h post-infusion. We found no significant alteration in the metabolism of APAP, mitochondrial, amino acids, and other thiol biomarkers with the two regimens. We examined APAP and purine metabolism in overdose patients who developed ALI. We showed the major APAP-metabolites and xanthine were significantly higher in patients with ALI. These biomarkers correlated well with alanine aminotransferase activity at admission. Receiver operating characteristic analysis showed that at admission, plasma APAP-metabolites and xanthine concentrations were predictive for ALI. In conclusion, a significantly higher redox thiol response with the modified NAC regimen at 12 h postdose suggests this regimen may produce greater antioxidant efficacy. At baseline, plasma APAP and purine metabolites may be useful biomarkers for early prediction of APAP-induced ALI.

Matched MeSH terms: ROC Curve
Brachial-ankle pulse wave velocity is associated with coronary calcium in young and middle-aged asymptomatic adults: The Kangbuk Samsung Health Study

Cainzos-Achirica M, Rampal S, Chang Y, Ryu S, Zhang Y, Zhao D, et al.

Atherosclerosis, 2015 Aug;241(2):350-6.
PMID: 26071657 DOI: 10.1016/j.atherosclerosis.2015.05.031

OBJECTIVE: To evaluate the association between brachial-ankle pulse wave velocity (baPWV), a convenient, non-radiating, readily available measurement of arterial stiffness, and coronary artery calcium (CAC), a reliable marker of coronary atherosclerosis, in a large sample of young and middle-aged asymptomatic adults; and to assess the incremental value of baPWV for detecting prevalent CAC beyond traditional risk factors.
METHODS: Cross-sectional study of 15,185 asymptomatic Korean adults who voluntarily underwent a comprehensive health screening program including measurement of baPWV and CAC. BaPWV was measured using an oscillometric method with cuffs placed on both arms and ankles. CAC burden was assessed using a multi-detector CT scan and scored following Agatston's method.
RESULTS: The prevalence of CAC > 0 and CAC > 100 increased across baPWV quintiles. The multivariable-adjusted odds ratios (95% CI) for CAC > 0 comparing baPWV quintiles 2-5 versus quintile 1 were 1.06 (0.87-1.30), 1.24 (1.02-1.50), 1.39 (1.15-1.69) and 1.60 (1.31-1.96), respectively (P trend < 0.001). Similarly, the relative prevalence ratios for CAC > 100 were 1.30 (0.74-2.26), 1.59 (0.93-2.71), 1.74 (1.03-2.94) and 2.59 (1.54-4.36), respectively (P trend < 0.001). For CAC > 100, the area under the ROC curve for baPWV alone was 0.71 (0.68-0.74), and the addition of baPWV to traditional risk factors significantly improved the discrimination and calibration of models for detecting prevalent CAC > 0 and CAC > 100.
CONCLUSIONS: BaPWV was independently associated with the presence and severity of CAC in a large sample of young and middle-aged asymptomatic adults. BaPWV may be a valuable tool for identifying apparently low-risk individuals with increased burden of coronary atherosclerosis.
KEYWORDS: Arterial stiffness; Atherosclerosis; Coronary artery calcium; Pulse wave velocity; Subclinical disease

Matched MeSH terms: ROC Curve
Fulltext Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study

Javaid A, Ahmad N, Afridi AK, Basit A, Khan AH, Ahmad I, et al.

Am J Trop Med Hyg, 2018 06;98(6):1629-1636.
PMID: 29611497 DOI: 10.4269/ajtmh.17-0936

To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429-0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522-0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595-0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69-69.32), 93.0% (95% CI = 89.69-95.52), and 97.6% (95% CI = 95.27-98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53-76.73), 51.5% (95% CI = 41.25-61.68), and 44.4% (95% CI = 34.45-54.78), respectively. Furthermore, patients' age of 41-60 (odds ratio [OR] = 0.202; 95% CI = 0.067-0.605) and > 60 years (OR = 0.051; 95% CI = 0.011-0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462-5.952), previous SLD use (OR = 0.277; 95% CI = 0.097-0.789), lung cavitation (OR = 0.196; 95% CI = 0.103-0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198-0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34-71.85) than at 4 months (OR = 14.13; 95% CI = 7.92-25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.

Matched MeSH terms: ROC Curve