Browse publications by year: 2024

  1. Erappa Rajj B, Nagaral M, Chintakindi S, Kumar R, Anqi AE, Rajhi AA, et al.
    ACS Omega, 2024 Apr 23;9(16):17878-17890.
    PMID: 38680352 DOI: 10.1021/acsomega.3c08822
    Aluminum metal cast composites (AMCCs) are frequently used in high-tech sectors such as automobiles, aerospace, biomedical, electronics, and others to fabricate precise and especially responsible parts. The mechanical and wear behavior of the metal matrix composites (MMCs) is anticipated to be influenced by the cooling agent's action and the cooling temperature. This research paper presents the findings of a series of tests to investigate the mechanical, wear, and fracture behavior of hybrid MMCs made of Al7075 reinforced by varying wt % of nano-sized Al2O3 and Gr and quenched with water and ice cubes. The heat-treated Al7075 alloy hybrid composites were evaluated for their hardness, tensile, and wear behavior, showcasing a significant process innovation. The heat treatment process greatly improved the hybrid composites' mechanical and wear performance. The samples quenched in ice attained the highest hardness of 119 VHN. There is a 45.37% improvement in the hardness of base alloy with the addition of 3% of Al2O3 and 1% of graphite particles. Further, the highest tensile and compression strengths were found in the ice-quenched 3% Al2O3 and 1% graphite hybrid composites with improvements of 34.2 and 48.83%, respectively, compared to the water-quenched base alloy. Under the samples quenched in ice, the mechanical and wear behavior improved. The tensile fractured surface showed voids, particle pullouts, and dimples. The worn-out surface of wear test samples of the created hybrid composite had micro pits, delamination layers, and microcracks.
  2. Damanhuri NH, Hairi NN, Ismail M, Jeganathan R, Karalasingam SD, Nasir MJM, et al.
    Cureus, 2024 Apr;16(4):e59152.
    PMID: 38680821 DOI: 10.7759/cureus.59152
    Background Spontaneous preterm birth (SPB) is a global public health concern with devastating health effects on SPB survivors. This study aimed to determine modifiable antenatal risk factors associated with SPB among women attending government healthcare facilities in Malaysia. Methodology A retrospective record review of 49,416 national obstetrics registry data from 2015 was conducted and analyzed using binary logistic regression based on six antenatal factor divisions. Results Mothers with pre-existing diabetes had higher odds (adjusted odds ratio (aOR) = 3.09) of delivering prematurely than mothers without diabetes. Mothers with chronic hypertension with superimposed pre-eclampsia (aOR = 2.51) and gestational hypertension (aOR = 1.44) had higher odds of experiencing preterm birth than mothers with no hypertension. Underweight mothers had higher odds (aOR = 1.27) of delivering prematurely than mothers with an ideal body mass index (18.5 to <25.0 kg/m2). Mothers with moderate anemia (hemoglobin level: 7 to <9 g/dL) had higher odds (aOR = 1.18) of preterm birth than mothers with normal hemoglobin levels (≥11 g/dL). Conclusions Maternal biomarkers, such as glucose level, blood pressure, BMI, and hemoglobin level, play an important role in reducing the rate of SPB in Malaysia. This study recommends strengthening pre-pregnancy, antenatal, and postpartum care through multidisciplinary and multi-agency team collaboration, addressing both modifiable and non-modifiable risk factors and adopting a dual approach that combines preventive and curative care.
  3. Yosep I, Suryani S, Mediani HS, Mardhiyah A, Maulana I, Hernawaty T, et al.
    J Multidiscip Healthc, 2024;17:1777-1790.
    PMID: 38680879 DOI: 10.2147/JMDH.S460343
    Bullying is a global problem in adolescents which has increased every year. One of the factors in the occurrence of bullying is the ability of interpersonal skills. This ability can build good relationships with assertive between adolescents and can prevent bullying. The purpose of this study is to describe assertiveness therapy for reducing bullying behavior and its impacts among adolescents. The method used in this study is scoping review. The search strategy used is PRISMA Extension for Scoping Reviews through three databases namely PubMed, CINAHL, and Scopus. The authors used inclusion criteria and exclusion criteria in the selection of articles. The major keywords used in the article search were bullying, assertiveness therapy, and adolescents. Data analysis used descriptive qualitative. The results showed that there were 10 articles that discussed assertive therapy. All articles show that assertiveness therapy can reduce bullying behavior and its impact significantly, such as reducing the impact of anxiety and increasing self-esteem. Assertiveness therapy methods carried out in the form of education, games, and role play. Education is carried out online and offline. Educational media is provided directly and through media such as educational videos which can be accessed at any time. Gender and cultural approaches are important aspects in the implementation of assertive therapy. Assertive therapy can improve interpersonal skills, social skills, empathy and assertiveness so that it can reduce bullying behavior and its impacts in adolescents. Then, this data becomes the basis for nurses to carry out assertive therapy as an effort to prevent and reduce bullying behavior in adolescents.
  4. Manimaran M, Teo YY, Kah JCY, Beishenaliev A, Loke YL, Foo YY, et al.
    Int J Nanomedicine, 2024;19:3697-3714.
    PMID: 38681091 DOI: 10.2147/IJN.S452085
    INTRODUCTION: Over 75% of clinical microbiological infections are caused by bacterial biofilms that grow on wounds or implantable medical devices. This work describes the development of a new poly(diallyldimethylammonium chloride) (PDADMAC)/alginate-coated gold nanorod (GNR/Alg/PDADMAC) that effectively disintegrates the biofilms of Staphylococcus aureus (S. aureus), a prominent pathogen responsible for hospital-acquired infections.

    METHODS: GNR was synthesised via seed-mediated growth method, and the resulting nanoparticles were coated first with Alg and then PDADMAC. FTIR, zeta potential, transmission electron microscopy, and UV-Vis spectrophotometry analysis were performed to characterise the nanoparticles. The efficacy and speed of the non-coated GNR and GNR/Alg/PDADMAC in disintegrating S. aureus-preformed biofilms, as well as their in vitro biocompatibility (L929 murine fibroblast) were then studied.

    RESULTS: The synthesised GNR/Alg/PDADMAC (mean length: 55.71 ± 1.15 nm, mean width: 23.70 ± 1.13 nm, aspect ratio: 2.35) was biocompatible and potent in eradicating preformed biofilms of methicillin-resistant (MRSA) and methicillin-susceptible S. aureus (MSSA) when compared to triclosan, an antiseptic used for disinfecting S. aureus colonisation on abiotic surfaces in the hospital. The minimum biofilm eradication concentrations of GNR/Alg/PDADMAC (MBEC50 for MRSA biofilm = 0.029 nM; MBEC50 for MSSA biofilm = 0.032 nM) were significantly lower than those of triclosan (MBEC50 for MRSA biofilm = 10,784 nM; MBEC50 for MRSA biofilm 5967 nM). Moreover, GNR/Alg/PDADMAC was effective in eradicating 50% of MRSA and MSSA biofilms within 17 min when used at a low concentration (0.15 nM), similar to triclosan at a much higher concentration (50 µM). Disintegration of MRSA and MSSA biofilms was confirmed by field emission scanning electron microscopy and confocal laser scanning microscopy.

    CONCLUSION: These findings support the potential application of GNR/Alg/PDADMAC as an alternative agent to conventional antiseptics and antibiotics for the eradication of medically important MRSA and MSSA biofilms.

    MeSH terms: Animals; Cell Line; Microbial Sensitivity Tests; Staphylococcal Infections/drug therapy; Mice; Metal Nanoparticles/chemistry; Methicillin-Resistant Staphylococcus aureus/drug effects; Methicillin-Resistant Staphylococcus aureus/physiology
  5. Chin WV, Khaw MJ
    POCUS J, 2024;9(1):41-43.
    PMID: 38681154 DOI: 10.24908/pocus.v9i1.16854
    Gas-forming pyogenic liver abscess (GFLPA) carries a high mortality rate. Early identification of the source of infection in sepsis results in better survival. Bedside point of care ultrasound (POCUS) can be used to help localize a source of infection. A 59-year-old man presented with systemic inflammatory response syndrome (SIRS) and was diagnosed with GFLPA on the initial encounter via clinical assessment and POCUS examination. After commencing antibiotics, optimal glucose control, adequate fluid resuscitation, and early infective source control, he achieved full recovery and was followed up in outpatient medical and surgical clinics. This case illustrates the role of POCUS as a diagnostic tool in sepsis and raises awareness among clinicians to recognize the features of GFLPA on POCUS.
  6. Vitamia C, Iftinan GN, Latarissa IR, Wilar G, Cahyanto A, Elamin KM, et al.
    Drug Des Devel Ther, 2024;18:1297-1312.
    PMID: 38681204 DOI: 10.2147/DDDT.S449370
    Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.
    MeSH terms: Biological Products/pharmacology; Biological Products/therapeutic use; Biological Products/chemistry; Humans
  7. Chon Han G, Iqbal T, Supramaniam G
    Cureus, 2024 Mar;16(3):e57044.
    PMID: 38681400 DOI: 10.7759/cureus.57044
    Neuromyelitis optica spectrum disorder (NMOSD) is a rare antibody-mediated neuroinflammatory disease of the central nervous system, typically manifesting in the optic nerves, spinal cord, and other regions of the central nervous system. We hereby report a case of a 16-year-old girl who presented with a six-month history of transverse myelitis with an acute episode of bilateral retrobulbar optic neuritis. MRI revealed patchy contrast enhancements over bilateral retrobulbar intraorbital optic nerves together with long-segment spinal cord hyperintensities (C2 to T2 level). Visual evoked potential testing during the acute presentation showed the absence of P100 bilaterally. However, both serum AQP4-IgG and MOG-IgG were reported to be negative. Despite remarkable improvement in bilateral optic nerve functions, she continued to have disabling bilateral lower limb spasticity, contractures, and loss of bilateral lower limb sensation after five cycles of plasma exchange. This case summarizes the challenges to diagnosing double seronegative NMOSD and its immediate therapeutic significance.
  8. Hanafi R, Zulkeflee RH, Hassan MN, Saidin NIS, Adzahar S, Hassan R
    Cureus, 2024 Mar;16(3):e57165.
    PMID: 38681415 DOI: 10.7759/cureus.57165
    Patients with myelodysplastic syndrome (MDS) often need platelet transfusions to address thrombocytopenia. The risk of alloimmunization, particularly in Rhesus (Rh) incompatibility between donors and recipients during platelet transfusions, is heightened, especially with whole blood-derived pooled platelets as opposed to apheresis platelets. Although the occurrence of alloimmunization from platelet transfusions is minimal, there is an ongoing debate about whether Rh immune globulin (RhIg) should be administered to Rhesus D (RhD)-negative recipients of RhD-positive platelet units. We present a unique case of anti-D alloimmunization in a 56-year-old patient with underlying MDS following multiple platelet transfusions but never received packed cell transfusion or anti-D immunoglobulin. Some studies advocate for RhIg administration in specific scenarios and for certain patient populations. This case underscores the importance of considering Rhesus compatibility or administering anti-D immunoglobulin in cases where frequent platelet transfusions are required.
  9. Loo GH, Muthkumaran G, Ritza Kosai N
    Cureus, 2024 Mar;16(3):e57152.
    PMID: 38681472 DOI: 10.7759/cureus.57152
    True parahiatal hernia is a type of diaphragmatic hernia in which herniation occurs through a defect in the diaphragm, adjacent to the normal oesophageal hiatus. Its reported incidence is very rare, and it is commonly misdiagnosed as paraoesophageal hernia. Although the clinical distinction between paraoesophageal and parahiatal hernia is difficult, it is essential to recognise these two separate entities clinically as their management differs. Clinical presentation of parahiatal hernia includes symptoms related to gastro-oesophageal reflux disease (GERD). Patients may also present emergently with symptoms of respiratory distress and chest symptoms. With that in mind, we describe a compelling case of a young lady who initially presented with symptoms suggestive of acute coronary syndrome. However, she was found to have an incarcerated parahiatal hernia.
  10. Taher MM, Abdalqader MA, Jahanath S, Nasharuddin NN, Al-Hamdan YNY
    J Surg Case Rep, 2024 Apr;2024(4):rjae209.
    PMID: 38681481 DOI: 10.1093/jscr/rjae209
    This research paper discusses a case in which stomach cancer was incidentally discovered during a bariatric surgery procedure. Bariatric surgery is well-known for its significant effects on weight loss and overall health enhancement, and its prevalence has been rising globally. While its primary aim is weight reduction, it also offers the chance for surgeons to detect and manage other medical conditions. In this specific case, a patient scheduled for bariatric surgery was incidentally discovered with stomach cancer, underscoring the significance of comprehensive operative assessments and vigilant monitoring during surgery.
  11. Geeri S, Kolakoti A, Samuel OD, Abbas M, Aigba PA, Ajimotokan HA, et al.
    Heliyon, 2024 Apr 30;10(8):e28986.
    PMID: 38681544 DOI: 10.1016/j.heliyon.2024.e28986
    The performance of a Pelton wheel is influenced by the jet created by the nozzle. Therefore, a Computational Fluid Dynamics (CFD) simulation was proposed. In this study, the significant output parameters (outlet velocity, outlet pressure, and tangential force component) and input parameters (different pressure and spear locations) were examined. In addition, the influencing parameters and their contributing percentages to the performance of the Pelton wheel were calculated using different optimisation techniques such as Taguchi Design of Experiments (DoE), Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), Grey Relational Analysis (GRA) and Criteria Importance Through Intercriteria Correlation (CRITIC). The effect of input factors on the output response was examined with DoE, and the results show that the inlet pressure had the most significant impact (97.38%, 99.18%, and 97.38%, respectively, for all different spear sites with a 99% confidence level). In terms of preference values, the TOPSIS and GRA results are comparable (best ranks for simulation runs #24 and #25 and least ranks for simulations #2 and #3, respectively). The CRITIC results for the pressure parameter are in good agreement with the Taguchi ANOVA analysis. The last spear location (5 mm after the nozzle outlet), with an inlet pressure of 413685 Pa generated the best result when employing the TOPSIS and GRA techniques. The outlet pressure of the nozzle was found to have a significant impact on the flow pattern of the Pelton Wheel based on the analysis of the CRITIC, Taguchi, and CFD results.
  12. Asghar A, Shahid M, Gang P, Khan NA, Fang Q, Xinzheng L
    Heliyon, 2024 Apr 30;10(8):e29491.
    PMID: 38681612 DOI: 10.1016/j.heliyon.2024.e29491
    BACKGROUND: White pitaya, a popular tropical fruit, is known for its high nutritional value. It is commercially cultivated worldwide for its potential use in the food and pharmaceutical industries. This study aims to assess the nutritional and phytochemical contents and biological potential of the South Chinese White Pitaya (SCWP) peel, flesh, and seed extracts.

    METHODS: Extract fractions with increasing polarity (ethyl acetate 

  13. Altawalah H, Alfouzan W, Al-Fadalah T, Zalzala MA, Ezzikouri S
    Heliyon, 2024 Apr 30;10(8):e29855.
    PMID: 38681623 DOI: 10.1016/j.heliyon.2024.e29855
    BACKGROUND: The prevalence of respiratory infections is largely underexplored in Kuwait. The aim of our study is to determine the etiology of infections from patients who are SARS-CoV-2 negative hospitalized with severe lower respiratory tract infections (LRTIs) in Kuwait during the coronavirus disease 2019 (COVID-19) pandemic.

    METHODS: We conducted an observational cross-sectional study among severe LRTI patients between September 2021 and March 2022. Respiratory samples from 545 non-COVID-19 severe LRTIs patients were prospectively evaluated with FTD Respiratory 21 Plus® real-time PCR, targeting 20 different viruses and 1 atypical bacterial pathogen.

    RESULTS: Among all 545 hospitalized cases, 411 (75.4 %) tested positive for at least one respiratory pathogen. The most common were rhinovirus (HRV) (32.7 %), respiratory syncytial virus (RSV) (20.9 %), metapneumovirus (HMPV) (14.1 %), bocavirus (13.2 %), and influenza A (12.7 %). The proportion of pathogens detected was highest in the under-5 age group, while HKU1 (44.4 %) predominated in the elderly (>50 years).

    CONCLUSION: Our study reveals a high prevalence of respiratory viruses in severe acute lower respiratory tract infections among non-COVID-19 hospitalized patients in Kuwait. HRV remains the main etiology affecting the country, particularly in infants. These results underscore the necessity of employing multiplex PCR for accurate diagnosis and describing the epidemiology of infections among severe lower respiratory tract infections. This will facilitate the use of specific antiviral therapy and help avoid excessive or inappropriate antibiotic therapy.

  14. Liu Y, Shang M, Jia C, Lim XJ, Ye Y
    Heliyon, 2024 Apr 30;10(8):e29819.
    PMID: 38681650 DOI: 10.1016/j.heliyon.2024.e29819
    Crowdsourcing logistics-based O2O (online to offline) has been increasingly implemented to help individuals or merchants tackle down the problem of intra city instant delivery in China. However, since insufficient control is imposed on free couriers, consumers are subjected to certain risks generated by the uneven service quality provided by free couriers, such that the continuous-use intention to adopt crowdsourcing logistics may be affected in an unexpected manner. A sampling survey was carried out in China's first- and second-tier cities, with 292 valid questionnaires collected. On that basis, the corresponding hypotheses were tested using the partial least squares (PLS) method. The findings of this study revealed that trust, perceived value, and satisfaction positively contributed to continuous-use intention, where trust contributed the most. Perceived risk exerted a significant negative effect on continuous use intention. Trust is capable of notably reducing perceived risk. Crowdsourcing logistics service quality is the critical driving variable of perceived value and satisfaction. Perceived risk has a negative moderating effect on satisfaction-continuous-use intention relationship, showing that the higher the perceived risk, the weaker the effect of satisfaction on continuous-use intention. Given perceived risk, a conceptual model was built by integrating e-CSI model (e-Customer Satisfaction Index Model) and PAM-ISC model (Post-acceptance Model of IS Continuance Model). From the integration, the findings of this study are expected to provide decision-making basis for crowdsourcing logistics platforms to help solve the "last mile" delivery problem.
  15. Krishnasamy S, Tang CY, Tan PH
    Indian J Thorac Cardiovasc Surg, 2024 May;40(3):332-340.
    PMID: 38681715 DOI: 10.1007/s12055-023-01600-w
    PURPOSE: Adenoid cystic carcinoma (ACC) of the trachea is a rare malignancy. We report a patient with ACC who underwent multimodal management including tracheal resection. A systematic review was also conducted on tracheal resection for ACC.

    METHODS: A literature search was conducted on MEDLINE, Embase, and PubMed using the search terms "trachea AND adenoid cystic carcinoma AND (surgery OR resection)" and articles from 2000 to August 2021 were identified. A total of 29 journal articles were included in the review.

    RESULTS: A total of 403 patients underwent surgery for tracheal ACCs. The mean age was 48.1 years and 54.7% were female. The commonest anatomical location was the lower trachea (46.9%). The mean time from symptom onset to diagnosis was 16.6 months with the commonest symptom being dyspnoea (52%). Fifty-eight percent of the patients had intraluminal growth. Tracheal resection (46.2%) and access via thoracotomy (41.4%) were the commonest procedures described. The mean length of trachea resected was 39.2 mm and the mean tumour size was 31.5 mm. 16.8% of lymph nodes were involved and 73.8% of cases had positive resection margins. The overall complication rate was 1.4-5.4% and the in-hospital mortality rate was 9.8%. The overall survival reported was 61.7% at 5 years and 54.6% at 10 years.

    CONCLUSION: Surgical resection followed by adjuvant radiotherapy is the mainstay in the treatment of tracheal ACC, notwithstanding the high rates of involved margins. Achieving tension-free anastomosis should be the first priority given the favourable response of adjuvant therapies in reducing recurrence rate and improving overall survival.

  16. Mengesha MG, Rajasekaran S, Ramachandran K, Sengodan VC, Yasin NF, Williams LM, et al.
    J Orthop, 2024 Sep;55:97-104.
    PMID: 38681829 DOI: 10.1016/j.jor.2024.04.018
    PURPOSE: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care.

    METHODS: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented.

    RESULTS: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics.

    CONCLUSION: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

  17. Dsouza NN, Chellasamy SK
    Iran J Microbiol, 2024 Feb;16(1):104-113.
    PMID: 38682059 DOI: 10.18502/ijm.v16i1.14879
    BACKGROUND AND OBJECTIVES: Multiple outbreaks over two decades and a high mortality rate have emphasized the Nipah virus (NiV) as a priority research area. The study focuses on identifying the mutational landscape in sequences from NiV human isolates from different geographical regions.

    MATERIALS AND METHODS: Thirty-seven NiV genomes of human samples from Malaysia, Bangladesh, and India were subjected to phylogeny and metagenomic analysis to decipher the genome variability using MEGA11 software and the meta-CATS web server. Using the Single-Likelihood Ancestor Counting method, the synonymous and nonsynonymous mutations among NiV genes were identified. Further, the nonsynonymous variations were used to identify mutations in all the NiV proteins.

    RESULTS: The NiV isolates were categorized into NiV-M, NiV-B, and NiV-I clades based on phylogenetic analysis. Metagenomic analysis revealed 1636 variations in the noncoding and coding regions of the genomes of the three clades of NiV. Further analysis of nonsynonymous mutations showed the phosphoprotein to be highly mutating, whereas the matrix protein was stable.

    CONCLUSION: Deciphering the mutation pattern using a comparative genomics approach for human isolates provided valuable insight into the stability of NiV proteins which can be further used for understanding variations in host-pathogen interaction and developing effective therapeutic measures.

  18. Fauzi A, Kifli N, Noor MHM, Hamzah H, Azlan A
    Open Vet J, 2024 Mar;14(3):750-758.
    PMID: 38682142 DOI: 10.5455/OVJ.2024.v14.i3.1
    BACKGROUND: Studies have reported that the phytochemical content of Mulberry (Morus alba Linn.) is influenced by the area where it grows. On the other hand, the study of the bioactivity and toxicity of mulberry leaves from Brunei Darussalam still needs to be completed. In particular, the investigation regarding the safe dose for Mulberry's application from Brunei Darussalam has yet to be studied. Hence, toxicity information must be considered even though the community has used it for generations.

    AIM: This study investigated Morus alba ethanolic leaf extract (MAE) to observe the acute toxicity in mice.

    METHODS: In particular, this study utilized 12 female Institute of Cancer Research mice, 8 weeks old, divided into 2 groups: the control group and the MAE group (2,000 mg/kg single dose). Physiology, hematology, biochemistry, and histology were analyzed during the study.

    RESULTS: The examination result indicated no mortality and behavioral changes throughout the testing period. However, the mice developed mild anemia and leukopenia, followed by decreased numbers of neutrophils, lymphocytes, and monocytes. In addition, the mice developed a mild hepatocellular injury, indicated by significant (p < 0.05) elevations of both alanine aminotransferase (ALT) and aspartate transaminase (AST). The histopathological findings of the liver were also consistent with the increment of ALT and AST, indicating mild hepatocellular necrosis through the eosinophilic cytoplasm and pyknosis (p > 0.05).

    CONCLUSION: It was evident that a single oral administration of MAE was not lethal for mice (LD50, which was higher than 2,000 mg/kg). However, the administration of high doses of MAE must be carefully considered.

    MeSH terms: Animals; Brunei; Female; Liver/drug effects; Liver/pathology; Mice, Inbred ICR*; Toxicity Tests, Acute; Mice
  19. Mohd Sani N, Aziz Z, Kamarulzaman A
    BioDrugs, 2024 May;38(3):405-423.
    PMID: 38472644 DOI: 10.1007/s40259-024-00649-2
    BACKGROUND: Hesitation about using biosimilars still exists among healthcare professionals (HCPs), despite extensive experience with their use. Globally, several health organisations and societies from various specialties have issued biosimilar position statements to guide the use of biosimilars in their specialties. However, it is uncertain how similar or different their positions or recommendations are or whether these positions have evolved with the increased experience and availability of new evidence.

    OBJECTIVES: The study aimed to describe and assess the recommendations of published position statements regarding several aspects of biosimilars across specialties and determine whether these positions have changed with the emergence of new evidence.

    METHODS: We systematically searched for published position statements of biosimilars in online databases and included statements written in English. The search was from the inception of the databases until May 2023. Two reviewers independently extracted the data. Only position statements that included recommendations to guide the use of biosimilars in clinical practice and were issued by health organisations and societies, including expert panels, were included. We synthesised recommendations on five aspects: prescribing practice, extrapolation of indication, interchangeability, treatment initiation with biosimilars in biologic-naïve patients, and pharmacovigilance.

    RESULTS: The review included 25 papers involving eight specialties, 16 of which were from European countries, 1 from an international organisation representing 49 countries, and 6 from various countries. The papers were published between 2009 and 2020, with 19 published between 2015 and 2020. Of the five aspects of biosimilars assessed, nearly half (11 of 25) of the papers at the time they were published did not base their positions on a scientific or evidence-based approach. Only 4 of the 25 position papers were identified as revisions of their previous papers. With increasing experience in biosimilars and the emergence of new evidence, about 60% (16 of 25) of the papers contained outdated recommendations, particularly on two aspects. They were extrapolations of indications and interchangeability (including switching). The recommendations for most papers for three other aspects were still appropriate. These were prescribing biosimilars by their brand name and active ingredient, initiating treatment with biosimilars in biologic-naïve patients, and monitoring the long-term safety of biosimilars through pharmacovigilance. For four of the revised papers, their position evolved from opposing indication extrapolation for biosimilars to accepting it, while the position of two papers shifted from not recommending biosimilar switching to permitting the practice. Meanwhile, most papers were against automatic substitution by pharmacists because the evidence for this practice was still limited.

    CONCLUSIONS: Across specialties, the variability among the position statements is seen for extrapolation of indications for biosimilars and interchangeability (including switching). This requires a revision, considering the latest evidence and growing experience with the use of biosimilars in extrapolated indications and with switching.

    MeSH terms: Humans; Practice Guidelines as Topic; Pharmacovigilance
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