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  1. Efficacy and resistance of different artemisinin-based combination therapies: a systematic review and network meta-analysis
    Mathenge PG, Low SK, Vuong NL, Mohamed MYF, Faraj HA, Alieldin GI, et al.
    Parasitol Int, 2020 Feb;74:101919.
    PMID: 31015034 DOI: 10.1016/j.parint.2019.04.016
    BACKGROUND: Malaria parasites have developed resistance to most of the known antimalarial drugs in clinical practice, with reports of artemisinin resistance emerging in South East Asia (SEA). We sort to find the status of artemisinin resistance and efficacy of different modalities of the current artemisinin-based combination therapies (ACTs).

    METHODS: We carried out a systematic search in 11 electronic databases to identify in vivo studies published between 2001 and 2017 that reported artemisinin resistance. This was then followed by A network meta-analysis to compare the efficacy of different ACTs. Quality assessment was performed using the Cochrane Risk of Bias (ROB) tool for randomized controlled trials and National Institute of Health (NIH) tool for cross-sectional studies. The study protocol was registered in PROSPERO under number CRD42018087574.

    RESULTS: With 8400 studies initially identified, 82 were eligible for qualitative and quantitative analysis. Artemisinin resistance was only reported in South East Asia. K13 mutation C580Y was the most abundant mutation associated with resistance having an abundance of 63.1% among all K13 mutations reported. Although the overall network meta-analysis had shown good performance of dihydroartemisinin piperaquine in the early years, a subgroup analysis of the recent years revealed a poor performance of the drug in relation to recrudescence, clinical failure and parasitological failure especially in the artemisinin resistant regions.

    CONCLUSION: With report of high resistance and treatment failure against the leading artemisinin combination therapy in South East Asia, it is imperative that a new drug or a formulation is developed before further spread of resistance.

    Matched MeSH terms: Drug Therapy, Combination; Malaria, Falciparum/drug therapy*
  2. Fulltext Use of corticosteroids in asthma and COPD patients with or without COVID-19
    Hasan SS, Capstick T, Zaidi STR, Kow CS, Merchant HA
    Respir Med, 2020 05 26;170:106045.
    PMID: 32843175 DOI: 10.1016/j.rmed.2020.106045
    The potential detrimental effects of steroids on the immune system to fight viral infections had always been a concern for patients on long term steroids in chronic conditions. A recent warning from WHO on systemic corticosteroid use amid COVID-19 raised suspicion among public and healthcare professionals regarding the safety of steroid use during the SARS-CoV-2 pandemic. The corticosteroids (inhaled and oral) are commonly prescribed in the management of asthma and COPD patients and any unsolicited changes in medications use may lead to potentially severe exacerbations and may risk patient lives. This article provides a critical review of clinical evidence and offers a detailed discussion on the safety and efficacy of corticosteroids in asthma and COPD patients, both with and without COVID-19.
    Matched MeSH terms: Asthma/drug therapy*; Pulmonary Disease, Chronic Obstructive/drug therapy*
  3. The potential correlation between patient-reported symptoms and the use of additional haemostatic medication for joint bleeding in haemophilia patients with inhibitors: a post hoc exploratory analysis of recombinant activated factor VII data from the ADEPT2 trial
    Lentz SR, Rangarajan S, Karim FA, Andersen PD, Arkhammar P, Rosu G, et al.
    Blood Coagul Fibrinolysis, 2017 Apr;28(3):224-229.
    PMID: 27427786 DOI: 10.1097/MBC.0000000000000584
    : Haemophilia treatment guidelines advocate early home-based treatment of acute bleeds. In the ADEPT2 trial, data were collected on the home treatment of bleeds with recombinant activated factor VII (rFVIIa) in haemophilia patients with inhibitors and self-reported bleeding-related symptoms. A total of 93% of all bleeds, and 91.5% of joint bleeds, were treated successfully with one to three doses of 90 μg/kg rFVIIa. However, some patients self-administered additional haemostatic medication (AHM) up to 48 h after the first rFVIIa treatment. The aim of this trial was to investigate the relationship between patient-reported symptoms, time to treatment initiation, and the use of AHM. A post hoc analysis was conducted on 177 joint bleeds and the patient-reported categorical symptoms of pain, swelling, mobility, tingling, and warmth, and the pain visual analogue scale (VAS) score. Analyses were descriptive and used logistic regression modelling. Complete symptom data were available for 141, 136, and 129 joint bleeds at 0 or 1, 3, and 6 h, respectively. Pain and pain VAS assessments were the best predictors of AHM use. Patients who self-administered AHM had higher mean pain VAS scores at each time point; both pain and pain VAS scores declined over time. Time to treatment initiation was an independent predictor for AHM use. Higher initial pain scores and longer time to treatment were the best predictors for administration of AHM. The observation that some patients chose to self-infuse in the face of declining levels of pain warrants further study to better understand the reasons behind patient decision-making.
    Matched MeSH terms: Hemarthrosis/drug therapy*; Hemophilia A/drug therapy*
  4. Folate-induced nanostructural changes of oligochitosan nanoparticles and their fate of cellular internalization by melanoma
    Musalli AH, Talukdar PD, Roy P, Kumar P, Wong TW
    Carbohydr Polym, 2020 Sep 15;244:116488.
    PMID: 32536388 DOI: 10.1016/j.carbpol.2020.116488
    This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil.
    Matched MeSH terms: Melanoma/drug therapy*; Skin Neoplasms/drug therapy*
  5. Congenital Tuberculosis Complicated by Hemophagocytic Lymphohistiocytosis
    Osowicki J, Wang S, McKenzie C, Marshall C, Gard J, Ke Juin W, et al.
    Pediatr Infect Dis J, 2016 Jan;35(1):108-10.
    PMID: 26398869 DOI: 10.1097/INF.0000000000000932
    We present the case of a male infant with congenital tuberculosis in a nonendemic setting complicated by hemophagocytic lymphohistiocytosis, who was treated successfully with antituberculous therapy and corticosteroids. We review the pediatric literature concerning the unusual association of these 2 rare conditions.
    Matched MeSH terms: Tuberculosis/drug therapy; Lymphohistiocytosis, Hemophagocytic/drug therapy
  6. Pemphigus vulgaris
    Nayak V, Kini R, Rao PK, Shetty U
    BMJ Case Rep, 2020 May 13;13(5).
    PMID: 32404374 DOI: 10.1136/bcr-2020-235410
    Matched MeSH terms: Mouth Diseases/drug therapy; Pemphigus/drug therapy
  7. Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases
    Tew XN, Xin Lau NJ, Chellappan DK, Madheswaran T, Zeeshan F, Tambuwala MM, et al.
    Chem Biol Interact, 2020 Feb 01;317:108947.
    PMID: 31968208 DOI: 10.1016/j.cbi.2020.108947
    Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
    Matched MeSH terms: Inflammation/drug therapy*; Respiratory Tract Diseases/drug therapy*
  8. Fulltext Anticancer Mechanism of Curcumin on Human Glioblastoma
    Wong SC, Kamarudin MNA, Naidu R
    Nutrients, 2021 Mar 16;13(3).
    PMID: 33809462 DOI: 10.3390/nu13030950
    Glioblastoma (GBM) is the most malignant brain tumor and accounts for most adult brain tumors. Current available treatment options for GBM are multimodal, which include surgical resection, radiation, and chemotherapy. Despite the significant advances in diagnostic and therapeutic approaches, GBM remains largely resistant to treatment, with a poor median survival rate between 12 and 18 months. With increasing drug resistance, the introduction of phytochemicals into current GBM treatment has become a potential strategy to combat GBM. Phytochemicals possess multifarious bioactivities with multitarget sites and comparatively marginal toxicity. Among them, curcumin is the most studied compound described as a potential anticancer agent due to its multi-targeted signaling/molecular pathways properties. Curcumin possesses the ability to modulate the core pathways involved in GBM cell proliferation, apoptosis, cell cycle arrest, autophagy, paraptosis, oxidative stress, and tumor cell motility. This review discusses curcumin's anticancer mechanism through modulation of Rb, p53, MAPK, P13K/Akt, JAK/STAT, Shh, and NF-κB pathways, which are commonly involved and dysregulated in preclinical and clinical GBM models. In addition, limitation issues such as bioavailability, pharmacokinetics perspectives strategies, and clinical trials were discussed.
    Matched MeSH terms: Brain Neoplasms/drug therapy*; Glioblastoma/drug therapy*
  9. Multifocal osteoarticular tuberculosis in a systemic lupus erythematosus (SLE) patient: a rarity or an underdiagnosed condition?
    Lim SL, Ong PS, Khor CG
    Mod Rheumatol Case Rep, 2020 07;4(2):237-242.
    PMID: 33086999 DOI: 10.1080/24725625.2020.1754567
    Tuberculosis (TB) and its association with rheumatic diseases have been widely recognised. Occurrence of multifocal skeletal involvement constitutes <5% of all skeletal TB cases. We present a Malay patient with multifocal osteoarticular TB (OATB). A 35 year-old SLE woman with background usage of corticosteroid therapy and Azathioprine presented with lupus nephritis flare. Renal biopsy revealed diffuse proliferative lupus nephritis and intravenous (IV) Cyclophosphamide 0.5 g/m2 (850 mg) was initiated. One week later, patient complained dorsum of left hand and right knee swelling. On physical examination, patient was afebrile and the left hand swelling was cystic in consistency while right knee was warm and tender. Erythrocyte Sedimentation Rate (ESR) was 50 mm/hr and C-Reactive Protein (CRP) was 9.4 mg/L. Her Mantoux test was positive with 20 mm induration. Wrist radiograph and chest radiograph was normal. Musculoskeletal ultrasound showed 4th extensor compartment tenosynovitis with Doppler signal and right knee effusion with synovial proliferation. Extensor tenosynovectomy and right knee aspiration was performed. Left hand excised tissue and right knee synovial fluid for acid-fast bacilli (AFB) stain, TB PCR, bacterial and fungal cultures were negative. Urgent histopathological examination of the excised tissue showed necrotising granulomatous inflammation. Patient was empirically started on TB treatment and subsequent mycobacterial culture confirmed the diagnosis of TB. The joints swelling resolved after one month of TB treatment. Multifocal OATB is an infrequent form of extrapulmonary TB and diagnosing OATB requires high index of suspicion particularly in SLE patient on immunosuppression. Prompt investigations are essential to the diagnosis of this rare condition for early initiation of anti-tuberculous therapy.
    Matched MeSH terms: Osteomyelitis/drug therapy; Tuberculosis, Osteoarticular/drug therapy
  10. Variability of plasma phenobarbitone concentration in Asian children in Singapore
    Lee HS
    Ther Drug Monit, 1984;6(2):182-8.
    PMID: 6740737
    In a study with 113 Asian children in which phenobarbitone was used as the sole antiepileptic drug in 75 children, including Chinese, Malays, and Indians, the mean phenobarbitone dosage required to produce a plasma level of 15 micrograms/ml was 5.2 mg/kg/day. While the mean plasma level/dose ratio varied, the differences between the three ethnic groups were not statistically significant. Also of little difference were the ratios between the male and female groups. For those patients with poor seizure control, however, the mean plasma level/dose ratio was significantly lower than in those whose seizures were controlled. Using additional anticonvulsant drugs concurrently with phenobarbitone in 40 children raised the mean plasma level/dose ratios significantly in each ethnic group. Further, the greater age level in those given additional antiepileptic drugs might have contributed slightly to a higher mean plasma level/dose ratio.
    Matched MeSH terms: Drug Therapy, Combination; Epilepsy/drug therapy
  11. Treatment of preeclampsia with hydroxychloroquine: a review
    Abd Rahman R, DeKoninck P, Murthi P, Wallace EM
    J Matern Fetal Neonatal Med, 2018 Feb;31(4):525-529.
    PMID: 28142291 DOI: 10.1080/14767058.2017.1289511
    In this review, we discuss the potential use of antimalarial drugs as an adjuvant therapy for preeclampsia, focusing on the mechanisms of action of this class of drugs in the context of preeclampsia. In particular, hydroxychloroquine has been shown to have various beneficial effects on patients with systemic lupus erythematosus. There are several pathways targeted by the antimalarial drugs that are similar to the pathophysiology of preeclampsia and hence offering opportunities to develop novel therapies to treat the disease. Given the safety profile of hydroxychloroquine in pregnancy, there is merit in exploring the efficacy of this drug as an adjuvant therapy in women with early onset preeclampsia.
    Matched MeSH terms: Lupus Erythematosus, Systemic/drug therapy; Pre-Eclampsia/drug therapy*
  12. A case of arrhythmogenic right ventricular cardiomyopathy with right ventricle thrombus: A case report
    Low QJ, Siaw C, Cheo SW, Kim HS, Benjamin Leo CL, Norliza O, et al.
    Med J Malaysia, 2020 07;75(4):452-454.
    PMID: 32724017
    Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited cardiomyopathy characterised by right ventricular dysfunction, ventricular arrhythmias and increased risk of sudden cardiac death. Due to the replacement of myocardium with fibro-fatty and fibrous tissue, patients with ARVC are prone to develop ventricular tachycardia. Histologically, it is often reported as the 'triangle of dysplasia' involving the inflow tract, outflow tract and apex of the right ventricle.2 We describe a 20-years-old patient who collapsed during a futsal match and was subsequently diagnosed to have ARVC with a right ventricular thrombus from cardiac magnetic resonance imaging.
    Matched MeSH terms: Thrombosis/drug therapy; Arrhythmogenic Right Ventricular Dysplasia/drug therapy
  13. Ointment tacrolimus for steroid resistant adenoviral nummular keratitis
    Jamaluddin Ahmad M, Lott PW, Khaliddin N, Singh S
    Med J Malaysia, 2020 07;75(4):461-463.
    PMID: 32724020
    A 33-year-old man presented with a four-day history of redness and blurring of vision of the right eye. A clinical diagnosis of adenoviral keratitis was made with a differential of microsporidia epithelial keratitis. The patient subsequently developed nummular keratitis which was resistant to topical steroids. He continued to develop multiple recurrences of the condition. Treatment with tacrolimus ointment was started as the patient had an elevated intraocular pressure due to prolonged steroid use. Tacrolimus ointment showed a favourable outcome in the management of recurrent nummular keratitis.
    Matched MeSH terms: Adenoviridae Infections/drug therapy; Keratitis/drug therapy*
  14. Hydroxyurea treatment for chronic myeloid leukaemia during pregnancy
    Jackson N, Shukri A, Ali K
    Br J Haematol, 1993 Sep;85(1):203-4.
    PMID: 8251394
    A patient being treated for chronic myeloid leukaemia with hydroxyurea became pregnant. Despite an increase in the dose of hydroxyurea (to 3 g per day) during the pregnancy, her white blood cell count could only be controlled at about 150 x 10(9)/l. A healthy baby girl was born at 37 weeks with normal blood counts and no evidence of congenital abnormality. There are now five reports of the use of hydroxyurea in pregnancy, and where leukapheresis is not available it may be the treatment of choice.
    Matched MeSH terms: Pregnancy Complications, Neoplastic/drug therapy*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*
  15. Fulltext Auditory Cinchonism in COVID Era
    Saniasiaya J, Kulasegarah J
    Ear Nose Throat J, 2020 Nov;99(9):597-598.
    PMID: 32744901 DOI: 10.1177/0145561320947255
    Matched MeSH terms: Pneumonia, Viral/drug therapy*; Coronavirus Infections/drug therapy*
  16. Fulltext Antimicrobial susceptibility of pathogenic mycoplasmas in chickens in Asia
    Morrow CJ, Kreizinger Z, Achari RR, Bekő K, Yvon C, Gyuranecz M
    Vet Microbiol, 2020 Nov;250:108840.
    PMID: 33068825 DOI: 10.1016/j.vetmic.2020.108840
    Mycoplasma synoviae (n = 26) and M. gallisepticum (n = 11) isolates were gained from 164 clinical samples collected from China, India, Indonesia, Malaysia, Philippines, Republic of Korea and Thailand. Most isolates were from commercial chicken production systems. A method of filtering (0.45 μm) samples immediately after collection was convenient allowing over a week for transit to the laboratory. Minimum inhibitory concentrations (MICs) were characterized by a broth microdilution method to enrofloxacin, difloxacin, oxytetracycline, chlortetracycline, doxycycline, tylosin, tilmicosin, tylvalosin, tiamulin, florfenicol, lincomycin, spectinomycin and lincomycin and spectinomycin combination (1:2). Increased MICs to various antimicrobials were seen in different isolates but appeared largely unrelated to the antimicrobial treatment histories. Overall, the results were similar to other MIC surveys around the world. Generally, low MICs to tetracyclines, tiamulin and tylvalosin were observed. Increased tilmicosin MICs were observed in both M. synoviae and M. gallisepticum isolates (≥64 μg/ml MIC90 values) and this was seen in all isolates with high tylosin MICs. Increases in lincomycin MICs were mostly associated with increases in tilmicosin MICs. The results also suggested that antimicrobial use after mycoplasma vaccination may interfere with vaccine strain persistence and efficacy (field strains were more commonly observed in flocks that had treatments after vaccination) and this area warrants more investigation. The study shows that isolation and MIC determination can be done from remote locations and suggests that this may provide information that will allow more effective use of antimicrobials or other methods of control of avian mycoplasma in chickens (e.g. live vaccines) and therefore more responsible use of antimicrobials from a one health perspective.
    Matched MeSH terms: Mycoplasma Infections/drug therapy; Poultry Diseases/drug therapy
  17. A case of a hand burns associated with a "wrap-around" pulse oximeter in an infant
    Hisham A, Hafizuddin Bin Salleh M, Ibrahim S, Mohd Yussof SJ
    Int Wound J, 2020 Aug;17(4):1097-1098.
    PMID: 32333718 DOI: 10.1111/iwj.13375
    Matched MeSH terms: Burns/drug therapy*; Hand Injuries/drug therapy*
  18. Probing the effects of fish oil on the delivery and inflammation-inducing potential of imiquimod
    Rehman K, Aluwi MF, Rullah K, Wai LK, Mohd Amin MC, Zulfakar MH
    Int J Pharm, 2015 Jul 25;490(1-2):131-41.
    PMID: 26003416 DOI: 10.1016/j.ijpharm.2015.05.045
    Imiquimod is a chemotherapeutic agent for many skin-associated diseases, but it has also been associated with inflammatory side effects. The aim of this study was to prevent the inflammatory effect of commercial imiquimod (Aldara(®)) by controlled release of imiquimod through a hydrogel/oleogel colloidal mixture (CA bigel) containing fish oil as an anti-inflammatory agent. Imiquimod permeability from Aldara® cream and bigel through mice skin was evaluated, and the drug content residing in the skin via the tape stripping technique was quantified. The fish oil fatty acid content in skin along with its lipophilic environment was also determined. An inflammation study was conducted using animal models, and Aldara(®) cream was found to potentially cause psoriasis-like inflammation, which could be owing to prolonged application and excessive drug permeation. Controlled release of imiquimod along with fish oil through CA bigel may have caused reduced imiquimod inflammation. NMR studies and computerized molecular modeling were also conducted to observe whether the fish oil and imiquimod formed a complex that was responsible for improving imiquimod transport and reducing its side effects. NMR spectra showed dose-dependent chemical shifts and molecular modeling revealed π-σ interaction between EPA and imiquimod, which could help reduce imiquimod inflammation.
    Matched MeSH terms: Inflammation/drug therapy; Psoriasis/drug therapy
  19. The effect of systemic ibuprofen on gingival inflammation in humans
    Taiyeb Ali TB, Waite IM
    J Clin Periodontol, 1993 Nov;20(10):723-8.
    PMID: 8276982
    This clinical trial investigated the influence of short-term ibuprofen therapy on the early phase of the treatment of adult chronic periodontitis. The subjects were 17 patients in good general health referred for specialist periodontal treatment, having moderate chronic adult periodontitis. A series of assessments were made every 2 weeks over an 8-week period, including evaluations of oral hygiene, gingival inflammation and probing pocket depths. All participants received oral hygiene instruction, and following baseline examinations, had half the dentition, chosen at random, treated by scaling and root planing. The patients were randomly distributed into 2 groups, a test group receiving a 14-day course of 800 mg ibuprofen daily, in 4 divided doses, and a control group who did not receive any drug regime. At the 2-week assessment following the drug regime, significantly greater reduction in gingival bleeding, colour and pocketing was detected in the test compared with the control group. The beneficial effects were less evident thereafter. Although clinical application of the regime used in this study would not be justified by these results, further research into anti-inflammatory agents as an adjunct in the treatment of periodontal diseases could be considered, in the light of the beneficial effect on gingivitis in the early phase of periodontal treatment reported.
    Matched MeSH terms: Gingivitis/drug therapy*; Periodontitis/drug therapy*
  20. Ensuring children with epilepsy get vitamin D
    Nurs Stand, 2016 Jul 20;30(47):17.
    PMID: 27440341 DOI: 10.7748/ns.30.47.17.s20
    Children with epilepsy need targeted strategies to ensure they get sufficient vitamin D, say researchers in Malaysia.
    Matched MeSH terms: Epilepsy/drug therapy*; Vitamin D Deficiency/drug therapy*
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