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1.
Langmuir ; 2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38329924

ABSTRACT

The search for high-performance catalysts to improve the catalytic activity for an oxygen reduction reaction (ORR) is crucial for developing a proton exchange membrane fuel cell. Using the first-principles method, we have performed computational screening on a series of transition metal (TM) atoms embedded in monolayer Nb2S2C to enhance the ORR activity. Through the scaling relationship and volcano plot, our results reveal that the introduction of a single Ni or Rh atom through substitutional doping into monolayer Nb2S2C yields promising ORR catalysts with low overpotentials of 0.52 and 0.42 V, respectively. These doped atoms remain intact on the monolayer Nb2S2C even at elevated temperatures. Importantly, the catalytic activity of the Nb2S2C doped with a TM atom can be effectively correlated with an intrinsic descriptor, which can be computed based on the number of d orbital electrons and the electronegativity of TM and O atoms.

2.
J Hosp Infect ; 137: 24-34, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37044283

ABSTRACT

Following recent viral outbreaks, there has been a significant increase in global demand for gloves. Biomedical research focuses increasingly on antimicrobial gloves to combat microbial transmission and hospital-acquired infections. Most antimicrobial gloves are manufactured using antimicrobial chemicals such as disinfectants, biocides and sanitizers. The design of antimicrobial gloves incorporates advanced technologies, including colloidal particles and nanomaterials, to enhance antimicrobial effectiveness. A category of antimicrobial gloves also explores and integrates natural antimicrobial benefits from animals, plants and micro-organisms. Many types of antimicrobial agents are available; however, it is crucial that the selected agent exhibits a broad spectrum of activity and is not susceptible to promoting resistance. Additionally, future research should focus on the potential effect of antimicrobial gloves on the skin microbiota and irritation during extended wear. Careful integration of the antimicrobial agent is essential to ensure optimal effectiveness without compromising the mechanical properties of the gloves.


Subject(s)
Anti-Infective Agents , Cross Infection , Disinfectants , Humans , Gloves, Surgical , Anti-Infective Agents/pharmacology , Technology , Gloves, Protective
3.
Occup Med (Lond) ; 72(7): 452-455, 2022 10 18.
Article in English | MEDLINE | ID: mdl-36256838

ABSTRACT

BACKGROUND: Aircrew are exposed to environmental pressure changes. In the Republic of Singapore Air Force (RSAF), applicants assessed to be at intermediate risk of otic barotrauma undergo a hypobaric chamber assessment ["trial of chamber" (TOC)] to functionally evaluate their suitability for military aircrew vocations. AIMS: To identify factors associated with TOC failure among applicants with otorhinolaryngological conditions. METHODS: All applicants to RSAF aircrew vocations who were assessed to be at intermediate risk of otic barotrauma over a 3-yr period were identified using the RSAF Aeromedical Centre's electronic database. Their medical records, as well as the TOC assessment records of the subset of applicants who underwent TOC, were reviewed for demographic data, clinical findings, and TOC outcomes. RESULTS: Of the 483 identified applicants, 374 (77%) had abnormal otoscopic findings, 103 (21%) had rhinitis symptoms, and 6 (1%) had previous ENT surgery. 123 (25%) underwent TOC, of which 20 (16%) failed. Holding other predictor variables constant, the odds of TOC failure increased by 0.79 per unit decrease in BMI (95% CI 0.63-0.99), and the odds of TOC failure increased by 0.93 per kg decrease in body weight (95% CI 0.87-1.00). An abnormal tympanogram was not a statistically significant predictor of TOC failure (OR 1.96, 95% CI 0.59-6.42). Of the 47 applicants who passed TOC and were eventually recruited, none subsequently developed otic barotrauma (mean follow-up, 3.3 yr ± 1.5 yr). CONCLUSIONS: Applicants with lower weight and BMI are more likely to develop otic barotrauma with environmental pressure change. Tympanometry cannot be reliably used to identify applicants who would more likely pass TOC.


Subject(s)
Aerospace Medicine , Barotrauma , Military Personnel , Humans , Barotrauma/epidemiology , Barotrauma/etiology , Singapore
4.
Int J Nephrol ; 2021: 6665901, 2021.
Article in English | MEDLINE | ID: mdl-34035962

ABSTRACT

BACKGROUND: The association between economic status and kidney disease is incompletely explored even in countries with higher economy (HE); the situation is complex in lower economies (LE) of South Asia and Southeast Asia (SA and SEA). METHODS: Fifteen countries of SA and SEA categorized as HE and LE, represented by the representatives of the national nephrology societies, participated in this questionnaire and interview-based assessment of the impact of economic status on renal care. RESULTS: Average incidence and prevalence of end-stage kidney disease (ESKD) per million population (pmp) are 1.8 times and 3.3 times higher in HE. Hemodialysis is the main renal replacement therapy (RRT) (HE-68%, LE-63%). Funding of dialysis in HE is mainly by state (65%) or insurance bodies (30%); out of pocket expenses (OOPE) are high in LE (41%). Highest cost for hemodialysis is in Brunei and Singapore, and lowest in Myanmar and Nepal. Median number of dialysis machines/1000 ESKD population is 110 in HE and 53 in LE. Average number of machines/dialysis units in HE is 2.7 times higher than LE. The HE countries have 9 times more dialysis centers pmp (median HE-17, LE-02) and 16 times more nephrologist density (median HE-14.8 ppm, LE-0.94 ppm). Dialysis sessions >2/week is frequently followed in HE (84%) and <2/week in LE (64%). "On-demand" hemodialysis (<2 sessions/week) is prevalent in LE. Hemodialysis dropout rates at one year are lower in HE (12.3%; LE 53.4%), death being the major cause (HE-93.6%; LE-43.8%); renal transplants constitute 4% (Brunei) to 39% (Hong Kong) of the RRT in HE. ESKD burden is expected to increase >10% in all the HE countries except Taiwan, 10%-20% in the majority of LE countries. CONCLUSION: Economic disparity in SA and SEA is reflected by poor dialysis infrastructure and penetration, inadequate manpower, higher OOPE, higher dialysis dropout rates, and lesser renal transplantations in LE countries. Utility of RRT can be improved by state funding and better insurance coverage.

5.
Br J Surg ; 108(2): 196-204, 2021 03 12.
Article in English | MEDLINE | ID: mdl-33711132

ABSTRACT

BACKGROUND: Laparoscopic liver resection for hepatocellular carcinoma (HCC) in Child-Pugh A cirrhosis has been demonstrated as beneficial. However, the role of laparoscopy in Child-Pugh B cirrhosis is undetermined. The aim of this retrospective cohort study was to compare open and laparoscopic resection for HCC with Child-Pugh B cirrhosis. METHODS: Data on liver resections were gathered from 17 centres. A 1 : 1 propensity score matching was performed according to 17 predefined variables. RESULTS: Of 382 available liver resections, 100 laparoscopic and 100 open resections were matched and analysed. The 90-day postoperative mortality rate was similar in open and laparoscopic groups (4.0 versus 2.0 per cent respectively; P = 0.687). Laparoscopy was associated with lower blood loss (median 110 ml versus 400 ml in the open group; P = 0.004), less morbidity (38.0 versus 51.0 per cent respectively; P = 0.041) and fewer major complications (7.0 versus 21.0 per cent; P = 0.010), and ascites was lower on postoperative days 1, 3 and 5. For laparoscopic resections, patients with portal hypertension developed more complications than those without (26 versus 12 per cent respectively; P = 0.002), and patients with a Child-Pugh B9 score had higher morbidity rates than those with B8 and B7 (7 of 8, 10 of 16 and 21 of 76 respectively; P < 0.001). Median hospital stay was 7.5 (range 2-243) days for laparoscopic liver resection and 18 (3-104) days for the open approach (P = 0.058). The 5-year overall survival rate was 47 per cent for open and 65 per cent for laparoscopic resection (P = 0.142). The 5-year disease-free survival rate was 32 and 37 per cent respectively (P = 0.742). CONCLUSION: Patients without preoperative portal hypertension and Child-Pugh B7 cirrhosis may benefit most from laparoscopic liver surgery.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Laparoscopy , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Blood Loss, Surgical/statistics & numerical data , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Disease-Free Survival , Female , Hepatectomy/adverse effects , Hepatectomy/methods , Hepatectomy/mortality , Humans , Hypertension, Portal/pathology , Laparoscopy/adverse effects , Laparoscopy/methods , Laparoscopy/mortality , Length of Stay/statistics & numerical data , Liver Cirrhosis/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Propensity Score , Retrospective Studies , Severity of Illness Index , Survival Analysis , Young Adult
6.
Int J Oral Maxillofac Surg ; 50(7): 887-894, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33272771

ABSTRACT

The aim of this study was to develop a third-generation modular mandible endoprosthesis that would experience less stress concentration at its stems compared to earlier generations, thereby minimizing micromotion and achieving long-term stability. In this three-piece modular design, different degrees of movement were incorporated between the endoprosthesis module interfaces. It was hypothesized that this unique feature would minimize stress concentration at the stems and hence promote osseointegration during the early phase of implantation. The endoprosthesis system was made of commercially pure grade 4 titanium, machined and surface-treated, then sterilized and implanted in segmental mandible defects of nine Macaca fascicularis. Clinical, radiological, histological, and histomorphometric evaluations were performed 4 months post-implantation. The endoprosthesis systems with a degree of movement incorporated, exhibited superior performance compared to the rigid system: 30.9-34.8 times higher percentage bone-implant contact (P< 0.0001) and 3.4-4.1 times higher percentage bone area (P<0.0001), with osseointegration noted at the posterior stems. However, fibrous tissue encapsulation was noted around the majority of the anterior stems in all groups. Although the degree of movement was favourable for improving bone healing and stability of the endoprosthesis system, more work needs to be done to investigate other strategies to further reduce loading on the endoprosthesis to achieve predictable osseointegration at the stems.


Subject(s)
Dental Implants , Animals , Dental Implantation, Endosseous , Dental Prosthesis Design , Humans , Macaca fascicularis , Mandible/diagnostic imaging , Mandible/surgery , Osseointegration , Prosthesis Design , Surface Properties , Titanium
7.
J Laryngol Otol ; 134(7): 603-609, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32713375

ABSTRACT

OBJECTIVE: This study aimed to evaluate the association between cochlear nerve canal dimensions and semicircular canal abnormalities and to determine the distribution of bony labyrinth anomalies in patients with cochlear nerve canal stenosis. METHOD: This was a retrospective study in which high-resolution computed tomography images of paediatric patients with severe-to-profound sensorineural hearing loss were reviewed. A cochlear nerve canal diameter of 1.5 mm or less in the axial plane was classified as stenotic. Semicircular canals and other bony labyrinth morphology and abnormality were evaluated. RESULTS: Cochlear nerve canal stenosis was detected in 65 out of 265 ears (24 per cent). Of the 65 ears, 17 ears had abnormal semicircular canals (26 per cent). Significant correlation was demonstrated between cochlear nerve canal stenosis and semicircular canal abnormalities (p < 0.01). Incomplete partition type II was the most common accompanying abnormality of cochlear nerve canal stenosis (15 out of 65, 23 per cent). CONCLUSION: Cochlear nerve canal stenosis is statistically associated with semicircular canal abnormalities. Whenever a cochlear nerve canal stenosis is present in a patient with sensorineural hearing loss, the semicircular canal should be scrutinised for presence of abnormalities.


Subject(s)
Hearing Loss, Sensorineural/etiology , Semicircular Canals/abnormalities , Vestibulocochlear Nerve Diseases/complications , Adolescent , Child , Child, Preschool , Cochlear Nerve/diagnostic imaging , Cochlear Nerve/pathology , Constriction, Pathologic , Female , Hearing Loss, Sensorineural/diagnostic imaging , Hearing Loss, Sensorineural/pathology , Humans , Infant , Male , Retrospective Studies , Semicircular Canals/diagnostic imaging , Semicircular Canals/pathology , Tomography, X-Ray Computed , Vestibulocochlear Nerve Diseases/diagnostic imaging , Vestibulocochlear Nerve Diseases/etiology , Vestibulocochlear Nerve Diseases/pathology
8.
Phys Chem Chem Phys ; 22(4): 2414-2423, 2020 Jan 29.
Article in English | MEDLINE | ID: mdl-31939468

ABSTRACT

The effects of solvents and temperature on the crystal formation were investigated for vinylidene fluoride/trifluoroethylene copolymer P(VDF-TrFE). Highly crystalline P(VDF-TrFE) thin films were fabricated by spin-casting using various polar solvents such as diethyl carbonate (DEC), methyl ethyl ketone (MEK), N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). Ferroelectric polarisation reversal of the P(VDF-TrFE) was evidenced by a displacement (D)-electric field (E) hysteresis loop measurement and supported by the presence of pyroelectric activity. The samples which were annealed above 100 °C gave elongated rod-like crystalline structures and the highest crystallinity, Xc of 83% was formed at 120 °C. Consequently, remnant polarisation (85 mC m-2) and the pyroelectric coefficient (30 µC m-2 K-1) were enhanced. Thus, annealing plays a substantial role in controlling the crystalline structure of P(VDF-TrFE) films regardless of the choice of solvent. Although, the crystalline structure control is almost independent of the solvent's polarity, the choice of solvent is essential in preparing a smoother film surface. Molecular dynamics of P(VDF-TrFE) are discussed from the observation of two dielectric relaxation processes, ß and γ related to the segmental micro-Brownian and local modes, respectively. The complete ferroelectric polarization reversal caused a reduction in the dielectric polarization and reduced the lattice spacing of the 110/200 planes.

9.
Growth Factors ; 38(3-4): 167-176, 2020.
Article in English | MEDLINE | ID: mdl-33719806

ABSTRACT

Cell entry of influenza A virus (IAV) was reported to be promoted by epidermal growth factor receptor (EGFR). On the other hand, binding of heparin-binding EGF-like growth factor (HB-EGF) to EGFR leads to internalisation and degradation of the receptors. This study aimed to testify whether or not HB-EGF-induced downregulation of EGFR could attenuate IAV cell entry and subsequently diminish the infection. Immunoblotting and plaque assay revealed that HB-EGF-induced degradation of EGFR led to reduction of viral matrix 1 protein level and suppressed virion production. In addition, immunoblotting and imaging flow cytometric analysis demonstrated that IAV-induced phosphorylation of STAT1 and its localisation to nucleus in the early stage of infection were inhibited by HB-EGF treatment. This suggested the potential of HB-EGF in modulating uncontrolled and exaggerated inflammatory response caused by IAV infection. Together these findings attest the potential of HB-EGF mediated endocytosis and degradation of EGFR as a novel anti-IAV strategy.


Subject(s)
Epidermal Growth Factor , Influenza A virus , Heparin , Heparin-binding EGF-like Growth Factor , Influenza A virus/metabolism , Phosphorylation
10.
Eur Ann Allergy Clin Immunol ; 52(3): 121-130, 2020 05.
Article in English | MEDLINE | ID: mdl-31668057

ABSTRACT

Summary: Introduction.The prevalence of allergic rhinitis in children with persistent otitis media with effusion in different countries varies between 82% to 93%. Many risk factors of otitis media with effusion has been studied and proven. However, its association with allergic rhinitis remains controversial. Objective. The main objective of this study is to determine the prevalence of allergic rhinitis in children with persistent otitis media with effusion. This study is also aimed to identify the risk factors of otitis media with effusion, common allergens associated with allergic rhinitis and determine the hearing threshold of children with otitis media with effusion. Methods.A hundred and thirty children were recruited. History taking, physical examination and hearing assessment were done in the first visit. Those with allergic rhinitis underwent skin prick test and treated with intranasal corticosteroid and antihistamine. A second examination and hearing assessment were then repeated after 3 months. Results.The prevalence of allergic rhinitis in children with persistent otitis media with effusion in this study was noted to be 80.3%. Among these children, dust mites appeared to be the most common allergen (87.7%). Another risk factor appeared to be families with more than 4 members per-household (96%). It is noted that that otitis media with effusion caused a hearing loss up to 33 dB. However, there was a statistically significant improvement of the hearing threshold during second visit after commencement of allergy treatment. It was also noted that the hearing threshold in allergic rhinitis group was significantly impaired compared to the non-allergic rhinitis group. Conclusions.Allergic rhinitis and larger family household appeared to be common risk factors in children with persistent otitis media with effusion. There is significant hearing loss noted in children suffering from otitis media with effusion and allergic rhinitis. The hearing threshold improved remarkably with medical therapy. This study hence clarifies the controversy on the association between allergic rhinitis and otitis media with effusion.


Subject(s)
Otitis Media with Effusion/epidemiology , Rhinitis, Allergic/epidemiology , Allergens/immunology , Child , Child, Preschool , Female , Humans , Malaysia/epidemiology , Male , Prevalence , Risk Factors , Skin Tests
11.
J Laryngol Otol ; 133(8): 662-667, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31267884

ABSTRACT

BACKGROUND: Retraction pocket theory is the most acceptable theory for cholesteatoma formation. Canal wall down mastoidectomy is widely performed for cholesteatoma removal. Post-operatively, each patient with canal wall down mastoidectomy has an exteriorised mastoid cavity, exteriorised attic, neo-tympanic membrane and shallow neo-middle ear. OBJECTIVE: This study aimed to clinically assess the status of the neo-tympanic membrane and the exteriorised attic following canal wall down mastoidectomy. METHODS: All post canal wall down mastoidectomy patients were recruited and otoendoscopy was performed to assess the neo-tympanic membrane. A clinical classification of the overall status of middle-ear aeration following canal wall down mastoidectomy was formulated. RESULTS: Twenty-five ears were included in the study. Ninety-two per cent of cases showed some degree of neo-tympanic membrane retraction, ranging from mild to very severe. CONCLUSION: After more than six months following canal wall down mastoidectomy, the degree of retracted neo-tympanic membranes and exteriorised attics was significant. Eustachian tube dysfunction leading to negative middle-ear aeration was present even after the canal wall down procedure. However, there was no development of cholesteatoma, despite persistent retraction.


Subject(s)
Abscess/surgery , Cholesteatoma, Middle Ear/surgery , Mastoidectomy/methods , Mastoiditis/surgery , Otitis Media/complications , Abscess/etiology , Adolescent , Adult , Aged , Child , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Treatment Outcome , Young Adult
13.
Ann Oncol ; 30(7): 1134-1142, 2019 07 01.
Article in English | MEDLINE | ID: mdl-30918950

ABSTRACT

BACKGROUND: Preclinical evidence suggests that MEK inhibition promotes accumulation and survival of intratumoral tumor-specific T cells and can synergize with immune checkpoint inhibition. We investigated the safety and clinical activity of combining a MEK inhibitor, cobimetinib, and a programmed cell death 1 ligand 1 (PD-L1) inhibitor, atezolizumab, in patients with solid tumors. PATIENTS AND METHODS: This phase I/Ib study treated PD-L1/PD-1-naive patients with solid tumors in a dose-escalation stage and then in multiple, indication-specific dose-expansion cohorts. In most patients, cobimetinib was dosed once daily orally for 21 days on, 7 days off. Atezolizumab was dosed at 800 mg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary end points included objective response rate, progression-free survival, and overall survival. RESULTS: Between 27 December 2013 and 9 May 2016, 152 patients were enrolled. As of 4 September 2017, 150 patients received ≥1 dose of atezolizumab, including 14 in the dose-escalation cohorts and 136 in the dose-expansion cohorts. Patients had metastatic colorectal cancer (mCRC; n = 84), melanoma (n = 22), non-small-cell lung cancer (NSCLC; n = 28), and other solid tumors (n = 16). The most common all-grade treatment-related adverse events (AEs) were diarrhea (67%), rash (48%), and fatigue (40%), similar to those with single-agent cobimetinib and atezolizumab. One (<1%) treatment-related grade 5 AE occurred (sepsis). Forty-five (30%) and 23 patients (15%) had AEs that led to discontinuation of cobimetinib and atezolizumab, respectively. Confirmed responses were observed in 7 of 84 patients (8%) with mCRC (6 responders were microsatellite low/stable, 1 was microsatellite instable), 9 of 22 patients (41%) with melanoma, and 5 of 28 patients (18%) with NSCLC. Clinical activity was independent of KRAS/BRAF status across diseases. CONCLUSIONS: Atezolizumab plus cobimetinib had manageable safety and clinical activity irrespective of KRAS/BRAF status. Although potential synergistic activity was seen in mCRC, this was not confirmed in a subsequent phase III study. CLINICALTRIALS.GOV IDENTIFIER: NCT01988896 (the investigators in the NCT01988896 study are listed in the supplementary Appendix, available at Annals of Oncology online).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics , Azetidines/administration & dosage , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neoplasms/metabolism , Neoplasms/pathology , Piperidines/administration & dosage , Prognosis , Survival Rate , Tissue Distribution , Young Adult
14.
Transplant Proc ; 50(10): 3564-3570, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30577239

ABSTRACT

BACKGROUND: Organ scarcity continues to be the main problem limiting the number of liver transplants performed. Outcomes of patients waitlisted for an organ in an Asian country with low organ donation rate have not been well evaluated. Our current policy of allocating 15 exception points to patients with hepatocellular carcinoma (HCC) to render them competitive for a transplant also requires review. METHODS: The waiting list registry and the organ transplant registry of a single institution in Asia were reviewed from December 2005 to June 2016 for all patients who underwent liver transplantation. Patient characteristics and outcomes of waitlist dropouts were evaluated. Statistical analyses were performed using SPSS version 20.0. RESULTS: One hundred seventy-three patients were waitlisted for a deceased donor liver-only transplant. The most common etiology of liver disease was hepatitis B, followed by cholestatic diseases. Approximately half of the patients had HCC (45.6%). Priority listing for transplant comprised 15.6% of cases. Median Model for End-Stage Liver Disease (MELD) at listing was 15, and median waiting time to transplant was 17 weeks (interquartile range = 6.5-43.5). Overall, 89 (51.4%) patients underwent liver transplantation and 68 (39.3%) dropped out. For patients with HCC, the most common cause of dropout was progression beyond University of California San Francisco transplant criteria (62.5%). The cumulative incidence of dropout at 3 months among patients with HCC who received exception MELD scores was 11%. This was higher than those listed with physiologic MELD of 14-16 points (7%) but lower than those with 17-19 points (16%). CONCLUSIONS: Hepatitis B-related liver disease and HCC comprise the majority of patients listed for liver transplant. Dropout rates are high and this is due to the lack of donor organs. The current policy of allocating 15 exception MELD points to patients with HCC within transplant criteria may underestimate the dropout risk of patients with HCC in our population.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Liver Transplantation , Tissue Donors/supply & distribution , Waiting Lists , Disease Progression , Female , Humans , Male , Middle Aged , Registries , Severity of Illness Index , Tissue and Organ Procurement , Waiting Lists/mortality
15.
Int J Nephrol ; 2018: 2138528, 2018.
Article in English | MEDLINE | ID: mdl-30327732

ABSTRACT

BACKGROUND: Hyperphosphatemia in chronic kidney disease (CKD) patients is often treated with calcium carbonate (CaCO3) despite the fact that CaCO3 is associated with increased calcium load and potentially increased cardiovascular risk. Alternative treatments with noncalcium-based phosphate binders do not increase the calcium load but are more costly. This study analyzes the cost-effectiveness of sevelamer versus CaCO3 for the treatment of hyperphosphatemia in stage III-V predialysis CKD patients in Malaysia. METHODS: A Markov decision model was adapted to simulate a hypothetical cohort of CKD patients requiring treatment for hyperphosphatemia. Survival was estimated by using efficacy data from the INDEPENDENT-CKD clinical trial. Cost data was obtained from Malaysian studies while health state utilities were derived from literature. Analysis was performed over lifetime duration from the perspective of the Ministry of Health Malaysia with 2013 as reference year. RESULTS: In the base case analysis, sevelamer treatment gained 6.37 life years (5.27 QALY) compared to 4.25 life years (3.54 QALY) with CaCO3. At 3% discount, lifetime costs were RM159,901 ($48,750) and RM77,139 ($23,518) on sevelamer and CaCO3, respectively. Incremental cost-effectiveness (ICER) of sevelamer versus CaCO3 was RM47,679 ($14,536) per QALY, which is less than the WHO threshold of three times GDP per capita (RM99,395) per QALY. Sensitivity analyses, both using scenario sensitivity analysis and probabilistic sensitivity analysis, showed the result to be robust. CONCLUSIONS: Our study finds that sevelamer is potentially cost-effective compared to CaCO3, for the treatment of hyperphosphatemia in predialysis CKD III-V. We propose that sevelamer should be an option in the treatment of Malaysian predialysis patients with hyperphosphatemia, particularly those with high calcium load.

16.
Nat Commun ; 9(1): 3931, 2018 09 26.
Article in English | MEDLINE | ID: mdl-30258081

ABSTRACT

There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.


Subject(s)
Mitochondria/drug effects , Niclosamide/therapeutic use , Proton Ionophores/therapeutic use , Tumor Suppressor Protein p53/deficiency , Animals , Apoptosis , Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 5-Lipoxygenase/metabolism , Arachidonic Acid , Calcium/metabolism , Coculture Techniques , HCT116 Cells , Humans , Lipid Metabolism , Metabolome/drug effects , Mice , Niclosamide/pharmacology , Proton Ionophores/pharmacology , Xenograft Model Antitumor Assays
17.
Transplant Proc ; 50(8): 2342-2345, 2018 Oct.
Article in English | MEDLINE | ID: mdl-30149932

ABSTRACT

Donor kidney volume (KV) is an increasingly important parameter evaluated before living kidney donation; however, KV measurements on computed tomographic (CT) scanning requires a manually intensive process of manual or semiautomatic segmentation of kidneys with interobserver variation. Renal artery diameter (RAD) is an easier marker to measure, and this study aims to investigate the relationship between donor RAD and KV. METHODS: A retrospective review of 77 patients who underwent living donor nephrectomy was conducted. Bilateral KVs were measured based on contrast-enhanced CT scan imaging, and renal artery maximum diameter was measured by direct visualization on the arterial phase of transverse CT sections. RESULTS: On regression analysis, there was a significant association between the right and left RADs and their ipsilateral KVs with a regression coefficient of 7.9 (95% CI, 1.3-14.5; P = .02) and 9.8 (95% CI, 3.3-16.3; P = .004), respectively. Mean total RAD correlated with total KV with a regression coefficient of 9.3 (95% CI, 3.8-14.7; P = .001) and weakly correlated with estimated glomerular filtration rate with a Pearson coefficient of .10. CONCLUSIONS: This study demonstrates that renal artery size is positively associated with KV and may be used as an easily measured surrogate marker for kidney size with its attended implications in living donor transplantation.


Subject(s)
Kidney Transplantation/methods , Living Donors , Renal Artery/diagnostic imaging , Adult , Female , Humans , Kidney/diagnostic imaging , Male , Middle Aged , Retrospective Studies , Tomography, X-Ray Computed/methods
20.
BJOG ; 124(1): 72-77, 2017 01.
Article in English | MEDLINE | ID: mdl-26931054

ABSTRACT

OBJECTIVE: To estimate the incidence of congenital syphilis in the UK. DESIGN: Prospective study. SETTING AND POPULATION: United Kingdom. METHODS: Children born between February 2010 and January 2015 with a suspected diagnosis of congenital syphilis were reported through an active surveillance system. MAIN OUTCOME MEASURES: Number of congenital syphilis cases and incidence. RESULTS: For all years, reported incidence was below the WHO threshold for elimination (<0.5/1000 live births). Seventeen cases (12 male, five female) were identified. About 50% of infants (8/17) were born preterm (<37 weeks' gestation): median birthweight 2000 g (865-3170 g). Clinical presentation varied from asymptomatic to acute disease, including severe anaemia, hepatosplenomegaly, rhinitis, thrombocytopaenia, skeletal damage, and neurosyphilis. One infant was deaf and blind. Median maternal age was 20 years (17-31) at delivery. Where maternal stage of infection was recorded, 6/10 had primary, 3/10 secondary and 1/10 early latent syphilis. Most mothers were white (13/16). Country of birth was recorded for 12 mothers: UK (n = 6), Eastern Europe (n = 3), Middle East (n = 1), and South East Asia (n = 2). The social circumstances of mothers varied and included drug use and sex work. Some experienced difficulty accessing health care. CONCLUSION: The incidence of congenital syphilis is controlled and monitored by healthcare services and related surveillance systems, and is now below the WHO elimination threshold. However, reducing the public health impact of this preventable disease in the UK is highly dependent on the successful implementation of WHO elimination standards across Europe. TWEETABLE ABSTRACT: Congenital syphilis incidence in the UK is at a very low level and well below the WHO elimination threshold.


Subject(s)
Syphilis, Congenital/epidemiology , Adult , Congenital Abnormalities/microbiology , Female , Humans , Incidence , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Male , Population Surveillance , Pregnancy , Pregnancy Outcome , Premature Birth/epidemiology , Prospective Studies , Syphilis/epidemiology , Syphilis, Congenital/diagnosis , United Kingdom/epidemiology
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