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Operating Rooms Scheduling for Elective Surgeries in a Hospital Affected by War-Related Incidents

Ali HH, Lamsali H, Othman SN

J Med Syst, 2019 Apr 10;43(5):139.
PMID: 30972511 DOI: 10.1007/s10916-019-1263-z

Hospital scheduling presents huge challenges for the healthcare industry. Various studies have been conducted in many different countries with focus on both elective and non-elective surgeries. There are important variables and factors that need to be taken into considerations. Different methods and approaches have also been used to examine hospital scheduling. Notwithstanding the continuous changes in modern healthcare services and, in particular, hospital operations, consistent reviews and further studies are still required. The importance of hospital scheduling, particularly, has become more critical as the trade-off between limited resources and overwhelming demand is becoming more evident. This situation is even more pressing in a volatile country where shootings and bombings in public areas happened. Hospital scheduling for elective surgeries in volatile country such as Iraq is therefore often interrupted by non-elective surgeries due to war-related incidents. Hence, this paper intends to address this issue by proposing a hospital scheduling model with focus on neuro-surgery department. The aim of the model is to maximize utilization of operating room while concurrently minimizing idle time of surgery. The study focused on neurosurgery department in Al-Shahid Ghazi Al-Hariri hospital in Baghdad, Iraq. In doing so, a Mixed-integer linear programming (MILP) model is formulated where interruptions of non-elective surgery are incorporated into the main elective surgery based model. Computational experiment is then carried out to test the model. The result indicates that the model is feasible and can be solved in reasonable times. Nonetheless, its feasibility is further tested as the problems size and the computation times is getting bigger and longer. Application of heuristic methods is the way forward to ensure better practicality of the proposed model. In the end, the potential benefit of this study and the proposed model is discussed.
Hepatitis B seroepidemiology and booster vaccination in pre-clinical medical students in a Malaysian university

Othman SN, Zainol Rashid Z, Abdul Wahab A, Abdul Samat MN, Ding CH, Ali UK

Malays J Pathol, 2018 Dec;40(3):295-302.
PMID: 30580360

INTRODUCTION: Infant hepatitis B vaccination was introduced into the Expanded Programme on Immunisation (EPI) in Malaysia in 1989. This study aimed to investigate seroprevalence of hepatitis B among UKM pre-clinical medical students, born between 1991 and 1995, and had their infant vaccination more than 20 years ago.
MATERIALS AND METHODS: A prospective, cross-sectional study involving 352 students, comprising 109 (31.0%) males and 243 (69.0%) females. Blood specimens were tested for anti-HBs, where levels of ≥10 mIU/mL was considered reactive and protective. Students with non-reactive levels were given a 20 μg HBV vaccine booster. Anti-HBs levels were tested six weeks after the first booster dose. Those with anti-HBs <10 mIU/mL were then given another two booster doses, at least one month apart. Anti-HBs levels were tested six weeks after the third dose.
RESULTS: Ninety-seven students (27.6%) had anti-HBs ranging from 10 to >1000 mIU/mL while 255 (72.4%) had anti-HBs <10 mIU/mL. After one booster dose, 208 (59.1%) mounted anti-HBs ≥10 mIU/mL. Among the remaining 47 (13.3%), all except two students (0.6%) responded following completion of three vaccination doses. They were negative for HBsAg and anti-HBcore antibody, thus regarded as non-responders.
CONCLUSIONS: Anti-HBs levels waned after 20 years post-vaccination, where more than 70% were within non-reactive levels. For healthcare workers, a booster dose followed by documenting anti-HBs levels of ≥10 mIU/mL may be recommended, to guide the management of post-exposure prophylaxis. Pre-booster anti-HBs testing may not be indicated. Serological surveillance is important in long-term assessment of HBV vaccination programs. No HBV carrier was detected.
Evaluation of IgM LAT and IgM ELISA as compared to microscopic agglutination test (MAT) for early diagnosis of Leptospira sp

Zin NM, Othman SN, Abd Rahman FR, Abdul Rachman AR

Trop Biomed, 2019 Dec 01;36(4):1071-1080.
PMID: 33597476

Leptospirosis is a worldwide zoonotic disease caused by spirochetes of the genus Leptospira. The clinical manifestation of leptospirosis is non-specific and frequently misdiagnosed as other illnesses. The aim of this study was to compare the diagnostic accuracies of two commercial tests for early diagnosis of Leptospira species: the IgM latex agglutination test (IgM LAT) and the IgM enzyme-linked immunosorbent assay (IgM ELISA). A total of 140 serum samples were obtained from patients suspected of leptospirosis at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC). These serum samples were tested for the presence of Leptospira sp. using IgM LAT, IgM ELISA and MAT. From Table 1, IgM LAT showed 21% (n = 29) positive, 18% (n = 25) inconclusive and 61% (n = 86) negative, while IgM ELISA showed 6% (n = 8) positive, 6% (n = 8) inconclusive, 88% (n = 124) negative and MAT showed 11% (n = 16) positive, 47% (n = 65) inconclusive, 42% (n = 59) negative. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of IgM LAT were 68.8%, 57.6%, 30.6% and 87.2% respectively, while for IgM ELISA they were 37.5%, 89.8%, 50% and 84.1%, respectively as compared to MAT (Table 2). The results showed that IgM LAT had higher sensitivity but lower specificity compared to IgM ELISA. In conclusion, IgM LAT can be useful as an early screening test for early diagnosis of Leptospira sp., while IgM ELISA is a suitable method for reducing false negative detection of Leptospira sp. As both tests show moderate percentages (~65%) in accuracy, an additional test is required for better detection of Leptospira sp.
Fulltext Identification of Predictive DNA Methylation Biomarkers for Chemotherapy Response in Colorectal Cancer

Baharudin R, Ab Mutalib NS, Othman SN, Sagap I, Rose IM, Mohd Mokhtar N, et al.

Front Pharmacol, 2017;8:47.
PMID: 28243201 DOI: 10.3389/fphar.2017.00047

Resistance to 5-Fluorouracil (5-FU) is a major obstacle to the successful treatment of colorectal cancer (CRC) and posed an increased risk of recurrence. DNA methylation has been suggested as one of the underlying mechanisms for recurrent disease and its contribution to the development of drug resistance remains to be clarified. This study aimed to determine the methylation phenotype in CRC for identification of predictive markers for chemotherapy response. We performed DNA methylation profiling on 43 non-recurrent and five recurrent CRC patients using the Illumina Infinium HumanMethylation450 Beadchip assay. In addition, CRC cells with different genetic backgrounds, response to 5-FU and global methylation levels (HT29 and SW48) were treated with 5-FU and DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC). The singular and combined effects of these two drug classes on cell viability and global methylation profiles were investigated. Our genome-wide methylation study on the clinical specimens showed that recurrent CRCs exhibited higher methylation levels compared to non-recurrent CRCs. We identified 4787 significantly differentially methylated genes (P < 0.05); 3112 genes were hyper- while 1675 genes were hypomethylated in the recurrent group compared to the non-recurrent. Fifty eight and 47 of the significantly hypermethylated and hypomethylated genes have an absolute recurrent/non-recurrent methylation difference of ≥20%. Most of the hypermethylated genes were involved in the MAPK signaling pathway which is a key regulator for apoptosis while the hypomethylated genes were involved in the PI3K-AKT signaling pathway and proliferation process. We also demonstrate that 5-azadC treatment enhanced response to 5-FU which resulted in significant growth inhibition compared to 5-FU alone in hypermethylated cell lines SW48. In conclusion, we found the evidence of five potentially biologically important genes in recurrent CRCs that could possibly serve as a new potential therapeutic targets for patients with chemoresistance. We postulate that aberrant methylation of CCNEI, CCNDBP1, PON3, DDX43, and CHL1 in CRC might be associated with the recurrence of CRC and 5-azadC-mediated restoration of 5-FU sensitivity is mediated at least in part by MAPK signaling pathway.
Fulltext Integrated microRNA, gene expression and transcription factors signature in papillary thyroid cancer with lymph node metastasis

Ab Mutalib NS, Othman SN, Mohamad Yusof A, Abdullah Suhaimi SN, Muhammad R, Jamal R

PeerJ, 2016;4:e2119.
PMID: 27350898 DOI: 10.7717/peerj.2119

Background. Papillary thyroid carcinoma (PTC) is the commonest thyroid malignancy originating from the follicle cells in the thyroid. Despite a good overall prognosis, certain high-risk cases as in those with lymph node metastasis (LNM) have progressive disease and poorer prognosis. MicroRNAs are a class of non-protein-coding, 19-24 nucleotides single-stranded RNAs which regulate gene expression and these molecules have been shown to play a role in LNM. The integrated analysis of miRNAs and gene expression profiles together with transcription factors (TFs) has been shown to improve the identification of functional miRNA-target gene-TF relationships, providing a more complete view of molecular events underlying metastasis process. Objectives. We reanalyzed The Cancer Genome Atlas (TCGA) datasets on PTC to identify differentially expressed miRNAs/genes in PTC patients with LNM-positive (LNM-P) versus lymph node negative (LNN) PTC patients and to investigate the miRNA-gene-TF regulatory circuit that regulate LNM in PTC. Results. PTC patients with LNM (PTC LNM-P) have a significantly shorter disease-free survival rate compared to PTC patients without LNM (PTC LNN) (Log-rank Mantel Cox test, p = 0.0049). We identified 181 significantly differentially expressed miRNAs in PTC LNM-P versus PTC LNN; 110 were upregulated and 71 were downregulated. The five topmost deregulated miRNAs were hsa-miR-146b, hsa-miR-375, hsa-miR-31, hsa-miR-7-2 and hsa-miR-204. In addition, 395 miRNAs were differentially expressed between PTC LNM-P and normal thyroid while 400 miRNAs were differentially expressed between PTC LNN and normal thyroid. We found four significant enrichment pathways potentially involved in metastasis to the lymph nodes, namely oxidative phosphorylation (OxPhos), cell adhesion molecules (CAMs), leukocyte transendothelial migration and cytokine-cytokine receptor interaction. OxPhos was the most significantly perturbed pathway (p = 4.70E-06) involving downregulation of 90 OxPhos-related genes. Significant interaction of hsa-miR-301b with HLF, HIF and REL/NFkB transcription factors were identified exclusively in PTC LNM-P versus PTC LNN. Conclusion. We found evidence of five miRNAs differentially expressed in PTC LNM-P. Alteration in OxPhos pathway could be the central event in metastasis to the lymph node in PTC. We postulate that hsa-miR-301b might be involved in regulating LNM in PTC via interactions with HLF, HIF and REL/NFkB. To the best of our knowledge, the roles of these TFs have been studied in PTC but the precise role of this miRNA with these TFs in LNM in PTC has not been investigated.
Diagnostic performance of COVID-19 serology assays

Zainol Rashid Z, Othman SN, Abdul Samat MN, Ali UK, Wong KK

Malays J Pathol, 2020 Apr;42(1):13-21.
PMID: 32342927

INTRODUCTION: The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19.
MATERIALS AND METHODS: A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently.
RESULTS: From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed.
CONCLUSIONS: There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.
Fulltext Smell Outcome and Seropositivity Titre in Post-COVID-19 Patients

Harminder Singh SK, Husain S, Wan Hamizan AK, Zahedi FD, Othman SN, Zainol Rashid Z

ORL J Otorhinolaryngol Relat Spec, 2023;85(6):305-311.
PMID: 37473733 DOI: 10.1159/000531222

INTRODUCTION: The aims of the study were to perform an olfactory assessment on patients active and post-COVID-19 using the culturally adapted Malaysian version Sniffin' Sticks identification smell test (mSS-SIT), to evaluate the patient olfactory outcome using a Malay short version of the Questionnaire of Olfactory Disorders-Negative Statements (msQOD-NS), as well as to evaluate seropositive titre (IgG) response using automated serology method.
METHODS: Score for mSS-SIT was performed during the hospitalization, when patients had tested positive for SARS-CoV-2 (during COVID-19), and repeated after they had tested negative (after COVID-19). Also, each patient completed msQOD-NS and serology SARS-CoV-2 antibodies blood test was evaluated.
RESULTS: During COVID-19, 2 of our patients were anosmia (6.5%), 22 (70.9%) were hyposmia, and 7 (22.6%) were normosmia. We repeated mSS-SIT on these same patients after COVID-19, and none of these subjects were hyposmia or anosmia, as they achieved a score >12. All our patients had scored 21 using msQOD-NS, meaning no impact on quality of life as they had regained their normal olfactory function. In this study also, we obtained no correlation between smell test and seropositivity titre COVID-19, and antibody levels gradually decreased over time till 6 months and remained stable up to 12 months.
CONCLUSION: From this study, we know full recovery of the sense of smell can be expected post-COVID-19 infection and COVID-19 antibody persists in the body up to 12 months of infection.
Novel complex re-arrangement of ARG1 commonly shared by unrelated patients with hyperargininemia

Mohseni J, Boon Hock C, Abdul Razak C, Othman SN, Hayati F, Peitee WO, et al.

Gene, 2014 Jan 1;533(1):240-5.
PMID: 24103480 DOI: 10.1016/j.gene.2013.09.081

Hyperargininemia is a very rare progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. Until now, some mutations were reported worldwide and none of them were of Southeast Asian origins. Furthermore, most reported mutations were point mutations and a few others deletions or insertions.