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Using SERS-based microfluidic paper-based device (μPAD) for calibration-free quantitative measurement of AMI cardiac biomarkers

Lim WY, Goh CH, Thevarajah TM, Goh BT, Khor SM

Biosens Bioelectron, 2020 Jan 01;147:111792.
PMID: 31678828 DOI: 10.1016/j.bios.2019.111792

Recently, surface enhanced Raman scattering (SERS) has attracted much attention in medical diagnosis applications owing to better detection sensitivity and lower limit of detection (LOD) than colorimetric detection. In this paper, a novel calibration-free SERS-based μPAD with multi-reaction zones for simultaneous quantitative detection of multiple cardiac biomarkers - GPBB, CK-MB and cTnT for early diagnosis and prognosis of acute myocardial infarction (AMI) are presented. Three distinct Raman probes were synthesised, subsequently conjugated with respective detecting antibodies and used as SERS nanotags for cardiac biomarker detection. Using a conventional calibration curve, quantitative simultaneous measurement of multiple cardiac biomarkers on SERS-based μPAD was performed based on the characteristic Raman spectral features of each reporter used in different nanotags. However, a calibration free point-of-care testing device is required for fast screening to rule-in and rule-out AMI patients. Partial least squares predictive models were developed and incorporated into the immunosensing system, to accurately quantify the three unknown cardiac biomarkers levels in serum based on the previously obtained Raman spectral data. This method allows absolute quantitative measurement when conventional calibration curve fails to provide accurate estimation of cardiac biomarkers, especially at low and high concentration ranges. Under an optimised condition, the LOD of our SERS-based μPAD was identified at 8, 10, and 1 pg mL-1, for GPBB, CK-MB and cTnT, respectively, which is well below the clinical cutoff values. Therefore, this proof-of-concept technique shows significant potential for highly sensitive quantitative detection of multiplex cardiac biomarkers in human serum to expedite medical decisions for enhanced patient care.

Matched MeSH terms: Biomarkers/analysis
Diagnostic values of different cytokines in identifying tuberculous pleural effusion

Nguyen MH, Dao QM, Bui TTH, Le VHT

Trop Biomed, 2020 Jun 01;37(2):372-378.
PMID: 33612806

Interleukin (IL)-1 beta (IL-1β), IL-2, Interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α) in the pleural fluid are valuable biomarkers in early diagnosis of Tuberculous Pleural Effusion (TPE). This study aimed to analyze the diagnostic values of some cytokines (IFN-γ, TNF-α, IL-1β, and IL-2) in pleural fluid for identifying TPE in Vietnam. We performed a cross-sectional study on tuberculosis (TB) patients with pleural effusion. Pleural IFN-γ, TNF-α, IL-1β, IL-2 were measured by ELISA® Kit (Abcam, USA) on Biotek system. Receiver operating characteristic curves (ROC), an area under the curve (AUC), sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (ACC) of IFN-γ, TNF-α, IL-1β, IL-2 in identifying TBE were assessed. Among 386 patients, 234 (60,6%) had TPE, and 152 (39,4%) did not have TPE. The median of IL-2, TNF-α, and IFN-γ levels were significantly higher in TPE compared to the non-TPE group (p<0.05). AUC for IL-1β, IL-2, TNF-α, and IFN-γ were 0.54, 0.57, 0.62. 0.84 (p<0.05), respectively. The sensitivity of IL-1β, IL-2, TNF-α, and IFN-γ in the diagnosis of TPE were 82.1, 53.4, 77.8, and 80.3, while the specificity was 28,4, 69.7, 47.4, and 80.9, respectively. IFN-γ and TNF-α are potential biomarkers in diagnosing TPE.

Matched MeSH terms: Biomarkers/analysis
Fulltext Host-dependent molecular factors mediating SARS-CoV-2 infection to gain clinical insights for developing effective targeted therapy

Shafi G, Desai S, Srinivasan K, Ramesh A, Chaturvedi R, Uttarwar M

Mol Genet Genomics, 2021 May;296(3):501-511.
PMID: 33743061 DOI: 10.1007/s00438-021-01774-1

Coronavirus disease 2019 (COVID-19), a recent viral pandemic that first began in December 2019, in Hunan wildlife market, Wuhan, China. The infection is caused by a coronavirus, SARS-CoV-2 and clinically characterized by common symptoms including fever, dry cough, loss of taste/smell, myalgia and pneumonia in severe cases. With overwhelming spikes in infection and death, its pathogenesis yet remains elusive. Since the infection spread rapidly, its healthcare demands are overwhelming with uncontrollable emergencies. Although laboratory testing and analysis are developing at an enormous pace, the high momentum of severe cases demand more rapid strategies for initial screening and patient stratification. Several molecular biomarkers like C-reactive protein, interleukin-6 (IL6), eosinophils and cytokines, and artificial intelligence (AI) based screening approaches have been developed by various studies to assist this vast medical demand. This review is an attempt to collate the outcomes of such studies, thus highlighting the utility of AI in rapid screening of molecular markers along with chest X-rays and other COVID-19 symptoms to enable faster diagnosis and patient stratification. By doing so, we also found that molecular markers such as C-reactive protein, IL-6 eosinophils, etc. showed significant differences between severe and non-severe cases of COVID-19 patients. CT findings in the lungs also showed different patterns like lung consolidation significantly higher in patients with poor recovery and lung lesions and fibrosis being higher in patients with good recovery. Thus, from these evidences we perceive that an initial rapid screening using integrated AI approach could be a way forward in efficient patient stratification.

Matched MeSH terms: Biomarkers/analysis
Blood brain barrier and infection

Chaudhuri JD

Med Sci Monit, 2000 Nov-Dec;6(6):1213-22.
PMID: 11208482

The blood brain barrier (BBB) is a highly dynamic structure and consists of endothelial cells, which are characterized by the presence of tight junctions and relative lack of endocytic vesicles. The tight junctions are reinforced by the foot processes of the astrocytes. The BBB functions through these specialised structures, to maintain the environment of the brain in a steady state by regulating the influx and efflux of substances. The protective effect of the BBB is however, lost during bacterial and viral infections. The primary mechanism operative are an increase in the permeability of the BBB and/or direct invasion of the brain by microorganisms. Since the BBB is relatively impermeable to chemotherapeutic agents the treatment of CNS infections is difficult. This paper aims to examine the various mechanisms by which infection spreads to the brain, and suggest measures for successful drug delivery into the brain during infections.

Matched MeSH terms: Biomarkers/analysis
Transcriptome analysis of Burkholderia pseudomallei T6SS identifies Hcp1 as a potential serodiagnostic marker

Chieng S, Mohamed R, Nathan S

Microb Pathog, 2015 Feb;79:47-56.
PMID: 25616255 DOI: 10.1016/j.micpath.2015.01.006

Burkholderia pseudomallei, the causative agent of melioidosis, is able to survive extreme environments and utilizes various virulence factors for survival and pathogenicity. To compete and survive within these different ecological niches, B. pseudomallei has evolved specialized pathways, including the Type VI secretion systems (T6SSs), that have a role in pathogenesis as well as interbacterial interactions. We examined the expression profile of B. pseudomallei T6SS six gene clusters during infection of U937 macrophage cells. T6SS-5 was robustly transcribed while the other five clusters were not significantly regulated proposing the utility of T6SS-5 as a potential biomarker of exposure to B. pseudomallei. Transcription of T6SS regulators VirAG and BprB was also not significant during infection when compared to bacteria grown in culture. Guided by these findings, three highly expressed T6SS genes, tssJ-4, hcp1 and tssE-5, were expressed as recombinant proteins and screened against melioidosis patient sera by western analysis and ELISA. Only Hcp1 was reactive by both types of analysis. The recombinant Hcp1 protein was further evaluated against a cohort of melioidosis patients (n = 32) and non-melioidosis individuals (n = 20) sera and the data clearly indicates a higher sensitivity (93.7%) and specificity (100%) for Hcp1 compared to bacterial lysate. The detection of anti-Hcp1 antibodies in patients' sera indicating the presence of B. pseudomallei highlights the potential of Hcp1 to be further developed as a serodiagnostic marker for melioidosis.

Matched MeSH terms: Biomarkers/analysis*
Fulltext Differential expression of stem cell-like proteins in normal, hyperplastic and dysplastic oral epithelium

Barakat SM, Siar CH

J Appl Oral Sci, 2015 Jan-Feb;23(1):79-86.
PMID: 25760270 DOI: 10.1590/1678-775720140245

The identification of stem cells (SC) remains challenging. In the human oral mucosal epithelium, these cells are believed to be in the basal layer (stem cell niche), but their exact location is unclear. The aim of this study was to examine the dysplastic oral epithelium for these SC-like proteins in order to assess their diagnostic value as biomarkers complementing the histological grading of dysplasia.

Matched MeSH terms: Biomarkers/analysis
Associations between prenatal nicotine exposure, oxidative stress, and postpartum visceral fat

Loy SL, Jan Mohamed HJ

Women Health, 2014;54(2):145-60.
PMID: 24329183 DOI: 10.1080/03630242.2013.870632

This study aimed to examine the associations among prenatal nicotine exposure, oxidative stress, and postpartum visceral fat among women exposed to secondhand smoke (SHS). The study was conducted in Kelantan, Malaysia, from April 2010 to December 2012. Blood samples were collected in the second and third trimesters from 135 healthy pregnant women who were followed-up at delivery, 2 months, 6 months and 12 months postpartum. Maternal hair nicotine and oxidative stress markers during pregnancy were measured. Visceral fat was assessed by bioelectrical impedance. Multiple linear regression analysis revealed that maternal hair nicotine concentration was associated with increased DNA damage (tail moment: β=0.580, p=0.001) and decreased glutathione peroxidase (β=-12.100; p=0.009) in the second trimester of pregnancy. Increased DNA damage, protein oxidation and total antioxidant capacity in the second trimester were associated with 2, 6, and 12 months postpartum visceral fat. No direct association was found between prenatal hair nicotine level and postpartum visceral fat; however, these results suggest that any relation of SHS to visceral adiposity may be indirect, mediated via enhanced oxidative stress.

Matched MeSH terms: Biomarkers/analysis
Two-stage bile preparation with acetone for recovery of fluorescent aromatic compounds (FACs)

Karami A, Syed MA, Christianus A, Willett KL, Mazzeo JR, Courtenay SC

J Hazard Mater, 2012 Jul 15;223-224:84-93.
PMID: 22608400 DOI: 10.1016/j.jhazmat.2012.04.051

In this study we sought to optimize recovery of fluorescent aromatic compounds (FACs) from the bile of African catfish (Clarias gariepinus) injected with 10mg/kg benzo[a]pyrene (BaP). Fractions of pooled bile were hydrolyzed, combined with ten volumes of methanol, ethanol, acetonitrile, or acetone, centrifuged and supernatants were analyzed by high-performance liquid chromatography with fluorescent detection (HPLC/FL). As well, to test whether FACs were being lost in solids from the centrifugation, pellets were resuspended, hydrolyzed and mixed with six volumes of the organic solvent that produced best FAC recovery from the supernatant, and subjected to HPLC/FL. Highest FAC concentrations were obtained with 2000μl and 1250μl acetone for supernatants and resuspended pellets respectively. FACs concentrations were negatively correlated with biliary protein content but were unaffected by addition of bovine serum albumin (BSA) followed by no incubation indicating that the presence of proteins in the biliary mixture does not simply interfere with detection of FACs. In another experiment, efficiency of acetone addition was compared to two different liquid-liquid extractions (L-LEs). Acetone additions provided significantly higher biliary FACs than the L-LE methods. The new two-stage bile preparation with acetone is an efficient, inexpensive and easily performed method.

Matched MeSH terms: Biomarkers/analysis
Synthesis of α-hydroxyphosphonates and their antioxidant properties

Naidu KR, Kumar KS, Arulselvan P, Reddy CB, Lasekan O

Arch Pharm (Weinheim), 2012 Dec;345(12):957-63.
PMID: 23015406 DOI: 10.1002/ardp.201200192

A series of α-hydroxyphosphonates were synthesized from the reaction of aldehyde (1) with triethylphosphite (2) in the presence of oxone and evaluated for their antioxidant properties against lipid peroxidation, reduced glutathione, superoxide dismutase, and catalase. The majority of the compounds showed promising antioxidant activity. Diethyl anthracen-9-yl (hydroxy) methylphosphonate (3n) is the most potent and biologically active compound against free radicals.

Matched MeSH terms: Biomarkers/analysis
Toxoplasma gondii excretory secretory antigenic proteins of diagnostic potential

Saadatnia G, Mohamed Z, Ghaffarifar F, Osman E, Moghadam ZK, Noordin R

APMIS, 2012 Jan;120(1):47-55.
PMID: 22151308 DOI: 10.1111/j.1600-0463.2011.02810.x

Infection with Toxoplasma gondii is widespread and important in humans, especially pregnant women and immunosuppressed patients. A panel of tests is usually required for diagnosis toxoplasmosis. Excretory secretory antigen (ESA) is highly immunogenic, and thus it is a good candidate for investigation into new infection markers. ESA was prepared from tachyzoites of RH strain of T. gondii by mice intraperitoneal infection. Sera were obtained from several categories of individuals who differed in their status of anti-Toxoplasma IgM, IgG and IgG avidity antibodies. The ESA was subjected to SDS-PAGE, two-dimensional gel electrophoresis and Western blot analysis. Antigenic bands of approximate molecular weights of 12, 20 and 30 kDa, when probed with anti-human IgM-HRP and IgA-HRP, showed good potential as infection markers. The highest sensitivity of the bands was 98.7% with combination of IgM and IgA blots with sera of patients with anti-Toxoplasma IgM+ IgG+. The specificities were 84% and 70% with sera from other infections and healthy controls in IgM blots and IgA blots respectively. By mass spectrometry, the 12 kDa protein was identified as thioredoxin. The two top proteins identified for 20 kDa molecule were microneme protein 10 and dense granule protein 7; whereas that for 30 kDa were phosphoglycerate mutase 1 and phosphoglycerate mutase.

Matched MeSH terms: Biomarkers/analysis
Effects of nicotine administration and nicotine cessation on bone histomorphometry and bone biomarkers in Sprague-Dawley male rats

Hapidin H, Othman F, Soelaiman IN, Shuid AN, Mohamed N

Calcif. Tissue Int., 2011 Jan;88(1):41-7.
PMID: 20953592 DOI: 10.1007/s00223-010-9426-4

Nicotine is a major alkaloid of tobacco, which can increase free radical formation, leading to osteoporosis. The effects of nicotine administration and cessation on bone histomorphometry and biomarkers were studied in 28 Sprague-Dawley male rats. Rats aged 3 months and weighing 250-300 g were divided into four groups: control (C, normal saline for 4 months), nicotine for 2 months (N2), nicotine for 4 months (N4), and nicotine cessation (NC). The NC group was given nicotine for the first 2 months and then allowed to recover for the following 2 months without nicotine. Histomorphometric analysis was done using an image analyzer. ELISA kits were used to measure serum osteocalcin (bone formation marker) and pyridinoline (PYD, bone resorption marker) levels at month 0, month 2, and month 4. All test groups showed a significant decrease in BV/TV, Ob.S/BS, dLS/BS, MAR, BFR/BS, and osteocalcin levels and an increase in sLS/BS and PYD levels compared to group C. No significant differences were observed in all parameters measured among the test groups, except for MAR and BFR/BS. In conclusion, nicotine administration at a dose of 7 mg/kg for 2 and 4 months has detrimental effects on bone metabolism. Nicotine administration at 7 mg/kg for 2 months is sufficient to produce significant effects on bone histomorphometric parameters and biomarkers. In addition, prolonging the treatment for another 2 months did not show any significant differences. Cessation of nicotine for 2 months did not reverse the effects.

Matched MeSH terms: Biomarkers/analysis
Distribution of polycyclic aromatic hydrocarbons (PAHS) and phenolic endocrine disrupting chemicals in South and Southeast Asian mussels

Isobe T, Takada H, Kanai M, Tsutsumi S, Isobe KO, Boonyatumanond R, et al.

Environ Monit Assess, 2007 Dec;135(1-3):423-40.
PMID: 17370135

A comprehensive monitoring survey for polycyclic aromatic hydrocarbons (PAHs) and phenolic endocrine disrupting chemicals (EDCs) utilizing mussels as sentinel organisms was conducted in South and Southeast Asia as a part of the Asian Mussel Watch project. Green mussel (Perna viridis) samples collected from a total of 48 locations in India, Indonesia, Singapore, Malaysia, Thailand, Cambodia, Vietnam, and the Philippines during 1994-1999 were analyzed for PAHs, EDCs including nonylphenol (NP), octylphenol (OP) and bisphenol A (BPA), and linear alkylbenzenes (LABs) as molecular markers for sewage. Concentrations of NP ranged from 18 to 643 ng/g-dry tissue. The highest levels of NP in Malaysia, Singapore, the Philippines, and Indonesia were comparable to those observed in Tokyo Bay. Elevated concentrations of EDCs were not observed in Vietnam and Cambodia, probably due to the lower extent of industrialization in these regions. No consistent relationship between concentrations of phenolic EDCs and LABs were found, suggesting that sewage is not a major source of EDCs. Concentrations of PAHs ranged from 11 to 1,133 ng/g-dry, which were categorized as "low to moderate" levels of pollution. The ratio of methylphenanthrenes to phenanthrene (MP/P ratio) was >1.0 in 20 out of 25 locations, indicating extensive input of petrogenic PAHs. This study provides a bench-mark for data on the distribution of anthropogenic contaminants in this region, which is essential in evaluating temporal and spatial variation and effect of future regulatory measures.

Matched MeSH terms: Biomarkers/analysis
Fulltext Genotoxicity following Organophosphate Pesticides Exposure among Orang Asli Children Living in an Agricultural Island in Kuala Langat, Selangor, Malaysia

Sutris JM, How V, Sumeri SA, Muhammad M, Sardi D, Mohd Mokhtar MT, et al.

Int J Occup Environ Med, 2016 01;7(1):42-51.
PMID: 26772597 DOI: 10.15171/ijoem.2016.705

BACKGROUND: Agriculture is an important sector for the Malaysian economy. The use of pesticides in agriculture is crucial due to its function in keeping the crops from harmful insects. Children living near agricultural fields are at risk of pesticide poisoning.
OBJECTIVE: To evaluate the genotoxic risk among children who exposed to pesticides and measure DNA damage due to pesticides exposure.
METHODS: In a cross-sectional study 180 Orang Asli Mah Meri children aged between 7 and 12 years were studied. They were all living in an agricultural island in Kuala Langat, Selangor, Malaysia. The data for this study were collected via modified validated questionnaire and food frequency questionnaire, which consisted of 131 food items. 6 urinary organophosphate metabolites were used as biomarkers for pesticides exposure. For genotoxic risk or genetic damage assessment, the level of DNA damage from exfoliated buccal mucosa cells was measured using the comet assay electrophoresis method.
RESULTS: Out of 180 respondents, 84 (46.7%) showed positive traces of organophosphate metabolites in their urine. Children with detectable urinary pesticide had a longer tail length (median 43.5; IQR 30.9 to 68.1 μm) than those with undetectable urinary pesticides (median 24.7; IQR 9.5 to 48.1 μm). There was a significant association between the extent of DNA damage and the children's age, length of residence in the area, pesticides detection, and frequency of apple consumption.
CONCLUSION: The organophosphate genotoxicity among children is associated with the amount of exposure (detectability of urinary pesticide) and length of residence in (exposure) the study area.

Matched MeSH terms: Biomarkers/analysis
IgG anti-beta(2) glycoprotein I antibodies in Malaysian patients with antiphospholipid syndrome and systemic lupus erythematosus: prevalence and clinical correlations

Ong SG, Cheng HM, Soon SC, Goh E, Chow SK, Yeap SS

Clin Rheumatol, 2002 Sep;21(5):382-5.
PMID: 12223986 DOI: 10.1007/s100670200102

The aim of this study was to investigate the incidence of IgG anticardiolipin antibody (ACL) and IgG anti-beta(2) glycoprotein I antibody (anti-beta2GPI) positivity in patients with primary or secondary antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE), to assess the association between IgG ACL and anti-beta2GPI, and the relationship between the presence of ACL and anti-beta2GPI with the clinical manifestations of APS. IgG ACL and IgG anti-beta2GPI levels were measured in 51 SLE patients, 20 patients with SLE and APS (secondary APS) and 11 primary APS patients using commercially available ELISA kits. Relationships between laboratory data and clinical manifestations of the patients were examined. The incidence of IgG ACL positivity was significantly higher in primary (36.4%) and secondary (40%) APS than in SLE (13.7%) patients (P = 0.02). The incidence of IgG anti-beta2GPI positivity was significantly higher in primary (54.5%) and secondary (35%) APS than in SLE (7.8%) patients (P = 0.0006). Mean levels of IgG ACL and anti-beta2GPI were significantly higher in the primary and secondary APS than in the SLE patients (P = 0.002 for both). A significant relationship was found between IgG ACL and IgG anti-beta2GPI (P = 0.01, R(2) = 0.56). There was a significant correlation between the presence of IgG ACL and a history of thrombosis in the combined primary and secondary APS group, but not in SLE patients. In conclusion, in this study IgG ACL and IgG anti-beta2GPI are closely related and mean levels of IgG ACL and IgG anti-beta2GPI are higher in patients with either primary or secondary APS than in SLE patients.
Study site: Rheumatology Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Matched MeSH terms: Biomarkers/analysis
Fulltext Single-tube, dual channel pentaplexing for the identification of Candida strains associated with human infection

Jainlabdin MH, Batra A, Sánchez Paredes E, Hernández Hernández F, Fu G, Tovar-Torres J

Sci Rep, 2019 10 11;9(1):14692.
PMID: 31604994 DOI: 10.1038/s41598-019-51198-6

Invasive candidiasis is one of the most common nosocomial fungal infections worldwide. Delayed implementation of effective antifungal treatment caused by inefficient Candida diagnosis contributes to its notoriously high mortality rates. The availability of better Candida diagnostic tools would positively impact patient outcomes. Here, we report on the development of a single-tube, dual channel pentaplex molecular diagnostic assay based on Multiplex Probe Amplification (MPA) technology. It allows simultaneous identification of C. auris, C. glabrata and C. krusei, at species-level as well as of six additional albicans and non-albicans pathogenic Candida at genus level. The assay overcomes the one-channel one-biomarker limitation of qPCR-based assays. Assay specificities are conferred by unique biomarker probe pairs with characteristic melting temperatures; post-amplification melting curve analysis allows simple identification of the infectious agent. Alerting for the presence of C. auris, the well-characterised multi-drug resistant outbreak strain, will facilitate informed therapy decisions and aid antifungal stewardship. The MPA-Candida assay can also be coupled to a pan-Fungal assay when differentiation between fungal and bacterial infections might be desirable. Its multiplexing capacity, detection range, specificity and sensitivity suggest the potential use of this novel MPA-Candida assay in clinical diagnosis and in the control and management of hospital outbreaks.

Matched MeSH terms: Biomarkers/analysis
Fulltext Validity and reliability of anti-diabetic medication adherence scale among patients with diabetes in Baghdad, Iraq: a pilot study

Mikhael EM, Hussain SA, Shawky N, Hassali MA

BMJ Open Diabetes Res Care, 2019;7(1):e000658.
PMID: 31354953 DOI: 10.1136/bmjdrc-2019-000658

Background: Medication non-adherence is a common problem among patients with diabetes. Patient-reported medication adherence scales are the most commonly used method to assess patient medication adherence, but up to today there is no specific tool for assessing medication adherence among patients with diabetes in Arab countries. This study aimed to develop and validate a new tool for assessment of adherence to antidiabetic medications among Iraqi patients with diabetes.
Methods: The Iraqi Anti-Diabetic Medication Adherence Scale (IADMAS) consists of eight items. The face and content validity of the IADMAS were established via an expert panel. For convergent validity, the IADMAS was compared with the Medication Adherence Questionnaire (MAQ). For concurrent validity, the IADMAS was compared with glycosylated hemoglobin. A total of 84 patients with types 2 diabetes were recruited from a diabetes center in Baghdad, Iraq. Test-retest reliability was measured by readministering the IADMAS to the same patients 4 weeks later.
Results: Only 80 patients completed the study (response rate: 95%). Reliability analysis of the IADMAS showed a Cronbach's alpha value of 0.712, whereas that of the MAQ was 0.649. All items in the IADMAS showed no significant difference in the test-retest analysis, indicating that the IADMAS has stable reliability. There was no difference in the psychometric properties of the IADMAS and the MAQ. The sensitivity and specificity of the IADMAS were higher than that of the MAQ (100% vs 87.5% and 33.9% vs 29.7%, respectively).
Conclusion: The IADMAS developed in this study is a reliable and valid instrument for assessing antidiabetic medication adherence among Iraqi patients.

Matched MeSH terms: Biomarkers/analysis*
The effects of glycemic control on morbidity and survival among diabetic patients

Hammad MA, Syed Sulaiman SA, Abubakar U, Mohamed Noor DA

Diabetes Metab Syndr, 2019 01 16;13(2):1035-1040.
PMID: 31336440 DOI: 10.1016/j.dsx.2019.01.001

AIMS: The study intended to investigate the impact of controlled glycemia on morbidity and estimated 10-year survival (ES-10Y).
METHODS: A cross-sectional investigation was conducted at General Penang Hospital, Malaysia. Demographic criteria and laboratory tests of patients were investigated. Controlled glycemia (CG) was recognized as glycated hemoglobin (HbA1c) ≤7% depending on American Diabetes Association guidelines 2018. Charlson Comorbidity Index (CCI) was used to estimate the confounding influence of co-morbidities and predict ES-10Y. Data was managed by IBM-SPSS 23.0.
RESULTS: A total of 400 cases categorized to (44.25%) patients with CG, and (55.75%) cases had uncontrolled glycemia (UCG). HbA1c mean in CG and UCG group was (6.8 ± 0.9 vs 9.5 ± 1.6, P-value: 0.001). Fasting blood glucose was (7 ± 2.3 vs. 9.9 ± 4.3, P-value: 0.001) in CG and UCG group. CCI was (3.38 ± 2.38 vs. 4.42 ± 2.70, P-value: 0.001) and, ES-10Y was (62% vs 46.2%, p-value: 0.001) in CG vs. UCG respectively. Spearman test indicates a negative correlation between CG and CCI (r: 0.19, p-value: 0.001). Logistic regression confirmed HbA1c as a significant predictor of CCI (r2: 0.036, P-value: 0.001). CG has a positive correlation with survival (r: 0.16, P-value: 0.001) and logistic regression of survival (r2: 0.26, P-value: 0.001).
CONCLUSIONS: More than one-half of the investigated persons had UCG. Controlled HbA1c was associated with lower co-morbidities and higher ES-10Y.

Matched MeSH terms: Biomarkers/analysis*
Impact of Ramadan Focused Education Program on medications adjustment for patients with type 2 diabetes in a primary health care institution in Saudi Arabia

Tourkmani AM, Alharbi TJ, Bin Rsheed AM, AlRasheed AN, AlBattal SM, Abdelhay O, et al.

Diabetes Metab Syndr, 2018 08 02;13(1):161-165.
PMID: 30641690 DOI: 10.1016/j.dsx.2018.07.012

AIMS: To examine the impact of Ramadan Focused Education Program (RFEP) on medications adjustment in type 2 diabetes patients in Ramadan.
METHODS: This is a controlled, intervention based study. It was run on three phases: before, during, and after Ramadan on 262 type 2 diabetes patients. The intervention group (n = 140) received RFEP on medications doses & timing adjustment before and after Ramadan, while the control group (n = 122) received standard care.
RESULTS: The dose of insulin glargine was reduced from 42.51 ± 22.16 at the baseline to 40.11 ± 18.51-units during Ramadan (p = 0.002) in the intervention group while it remained the same in the control group before Ramadan and during Ramadan (38.51 ± 18.63 and 38.14 ± 18.46, P = 0.428, respectively). The hypoglycemia score was 14.2 ± (8.5) pre-Ramadan in the intervention and reduced to 6.36 ± 6.17 during Ramadan (p 

Matched MeSH terms: Biomarkers/analysis
Effects of the SGLT2 inhibitor dapagliflozin on proteinuria in non-diabetic patients with chronic kidney disease (DIAMOND): a randomised, double-blind, crossover trial

Cherney DZI, Dekkers CCJ, Barbour SJ, Cattran D, Abdul Gafor AH, Greasley PJ, et al.

Lancet Diabetes Endocrinol, 2020 07;8(7):582-593.
PMID: 32559474 DOI: 10.1016/S2213-8587(20)30162-5

BACKGROUND: SGLT2 inhibition decreases albuminuria and reduces the risk of kidney disease progression in patients with type 2 diabetes. These benefits are unlikely to be mediated by improvements in glycaemic control alone. Therefore, we aimed to examine the kidney effects of the SGLT2 inhibitor dapagliflozin in patients with proteinuric kidney disease without diabetes.
METHODS: DIAMOND was a randomised, double-blind, placebo-controlled crossover trial done at six hospitals in Canada, Malaysia, and the Netherlands. Eligible participants were adult patients (aged 18-75 years) with chronic kidney disease, without a diagnosis of diabetes, with a 24-h urinary protein excretion greater than 500 mg and less than or equal to 3500 mg and an estimated glomerular filtration rate (eGFR) of at least 25 mL/min per 1·73 m2, and who were on stable renin-angiotensin system blockade. Participants were randomly assigned (1:1) to receive placebo and then dapagliflozin 10 mg per day or vice versa. Each treatment period lasted 6 weeks with a 6-week washout period in between. Participants, investigators, and study personnel were masked to assignment throughout the trial and analysis. The primary outcome was percentage change from baseline in 24-h proteinuria during dapagliflozin treatment relative to placebo. Secondary outcomes were changes in measured GFR (mGFR; via iohexol clearance), bodyweight, blood pressure, and concentrations of neurohormonal biomarkers. Analyses were done in accordance with the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT03190694.
FINDINGS: Between Nov 22, 2017, and April 5, 2019, 58 patients were screened, of whom 53 (mean age 51 years [SD 13]; 32% women) were randomly assigned (27 received dapagliflozin then placebo and 26 received placebo then dapagliflozin). One patient discontinued during the first treatment period. All patients were included in the analysis. Mean baseline mGFR was 58·3 mL/min per 1·73 m2 (SD 23), median proteinuria was 1110 mg per 24 h (IQR 730-1560), and mean HbA1c was 5·6% (SD 0·4). The difference in mean proteinuria change from baseline between dapagliflozin and placebo was 0·9% (95% CI -16·6 to 22·1; p=0·93). Compared with placebo, mGFR was changed with dapagliflozin treatment by -6·6 mL/min per 1·73 m2 (-9·0 to -4·2; p<0·0001) at week 6. This reduction was fully reversible within 6 weeks after dapagliflozin discontinuation. Compared with placebo, bodyweight was reduced by 1·5 kg (0·03-3·0; p=0·046) with dapagliflozin; changes in systolic and diastolic blood pressure and concentrations of neurohormonal biomarkers did not differ significantly between dapagliflozin and placebo treatment. The numbers of patients who had one or more adverse events during dapagliflozin treatment (17 [32%] of 53) and during placebo treatment (13 [25%] of 52) were similar. No hypoglycaemic events were reported and no deaths occurred.
INTERPRETATION: 6-week treatment with dapagliflozin did not affect proteinuria in patients with chronic kidney disease without diabetes, but did induce an acute and reversible decline in mGFR and a reduction in bodyweight. Long-term clinical trials are underway to determine whether SGLT2 inhibitors can safely reduce the rate of major clinical kidney outcomes in patients with chronic kidney disease with and without diabetes.
FUNDING: AstraZeneca.

Matched MeSH terms: Biomarkers/analysis
Statins-related peripheral neuropathy among diabetic patients

Hammad MA, Syed Sulaiman SA, Alghamdi S, Mangi AA, Aziz NA, Mohamed Noor DA

Diabetes Metab Syndr, 2020 04 09;14(4):341-346.
PMID: 32305775 DOI: 10.1016/j.dsx.2020.04.005

BACKGROUND: Peripheral neuropathy (PN) is a complaint with often unidentified reasons. Some medicines, including statins therapy, are anticipated to be amongst the reasons for PN.
AIMS: This study intended to assess the association of peripheral neuropathy with statins therapy amongst Type 2 diabetic patients.
METHODS: At Penang General Hospital, 757 cases were categorized into two groups (564 with statins therapy and 193 without statins therapy). The diagnosis of PN was investigated retrospectively for a period of 10 years (2006-2016). Confounding risk factors as age, diabetes period, hypertension, glycemic control, other co-morbidity, and prescriptions were matched.
RESULTS: About 129 (22.9%) cases from 564 statins users had PN. Only 30 (15.5%) subjects had PN from 193 statins non-users. Chi-square test showed a significant variance among statins treatment cohort and statin-free cohort in the occurrence of PN (P-value: 0.001). Spearman's investigation presented a positive correlation (r: 0.078, p-value: 0.031) among statins use and PN prevalence. Binary logistic regression was statistically significant for statins therapy as a predictor of peripheral neuropathy incidence (r2: 0.006, p-value: 0.027) amid diabetic patients. The relative risk of peripheral neuropathy connected with statins therapy is (RR: 1.47, 95% CI: 1.02-2.11). The excess relative risk is 47.1%. While the absolute risk (AR) is 7.3% and the number needed to harm (NNH) is 14.
CONCLUSIONS: The study indicated a positive association between peripheral neuropathy and statins utilization. Peripheral neuropathy was higher amongst statins users than the statins-free group.

Matched MeSH terms: Biomarkers/analysis

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