Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 199
Filter
1.
Cureus ; 16(6): e62106, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38993397

ABSTRACT

INTRODUCTION:  Non-compliance to medications remains a challenging problem in schizophrenia. Newer strategies with high feasibility and acceptability are always being researched. This study aimed to assess the effectiveness of technology-based intervention in improving medication compliance in individuals with schizophrenia. METHOD: This was a prospective intervention study where participants were required to use the SuperMD smartphone application (Digital-Health Technologies Pte Ltd, Kuala Lumpur, Malaysia) for a month. A change in the Medication Adherence Rating Scale-Malay Translation (MARS-M) and Malay Translation of Drug Adherence Inventory-9 (MDAI-9) scores indicated a change in compliance and attitude to medication. Positive and Negative Syndrome Scale (PANSS) was used to assess change in symptoms and insight. Medication compliance was also obtained from the SuperMD application. Paired T-test was used to evaluate the significance of changes in mean scores of research variables over the study period. Wilcoxon signed-rank test was used to analyze the subscale of MDAI-9 and the change in PANSS score. The Kruskal-Wallis test was used to determine the effect of the change of insight on the level of compliance with medication. RESULTS: There were 36 participants in this study. The results showed statistically significant improvement in compliance (0.65, p ≤ 0.01) but not in attitude towards medication (0.78, p = 0.065). There was also an improvement in PANNS score (-2.58, P ≤ 0.01). There was no significant change in insight (χ2(2) = 3.802, p = 0.15).  Conclusion:The use of technology-based strategies like SuperMD is effective in improving medication compliance for individuals with schizophrenia.

2.
Cureus ; 16(5): e60715, 2024 May.
Article in English | MEDLINE | ID: mdl-38903371

ABSTRACT

INTRODUCTION: The Drug Attitude Inventory 9 (DAI-9) is a nine-item self-rated questionnaire. The questionnaire assessed positive and negative attitudes of patients toward taking medication, presence of medication side effects and perceived autonomy in treatment decision. Aim: This study aimed to validate the psychometric properties of the Malay translation of Drug Attitude Inventory 9 (MDAI-9). METHOD: DAI-9 was translated from English to Malay via forward and backward translation process to produce MDAI-9. MDAI-9 was then validated on patients with psychosis who were attending psychiatry out-patient clinics. Results: There were 54 participants in this study. The subscale (attitude towards psychotropic medications) has a Cronbach's α of 0.93, whereas the subscale that assesses the presence of side effect problems has a Cronbach's α of 0.86. Exploratory factor analysis supported a two-factor model. Kaiser-Meyer-Olkin's measure of sampling adequacy was 0.64 and Bartlett's test of sphericity was significant (​​​​​X2   (36) = 281.8, p <0.001). CONCLUSION: In conclusion, MDAI-9 is reliable and valid.

3.
Cureus ; 16(5): e60570, 2024 May.
Article in English | MEDLINE | ID: mdl-38770051

ABSTRACT

INTRODUCTION: The Medication Adherence Rating Scale (MARS) is a self-rated questionnaire that assesses medication compliance. AIM: This study aimed to validate the Malaysian language translation of the MARS (MARS-M). METHOD: The original scale was translated to Malay via forward and backward translation process. The psychometric properties of the MARS-M were validated on clinical samples (N = 54). RESULTS: The MARS-M was filled by 54 participants. Exploratory factor analysis supported a two-factor model. Factor 1 of the MARS-M consisted of four items (α = 0.84), while factor 2 consisted of three items (α = 0.78).Kaiser-Meyer-Olkin measure of sampling adequacy was 0.60, and Bartlett's test of sphericity was significant (X2 (28) = 66.4, p <0.001). CONCLUSION: The MARS-M is reliable and valid.

5.
Arch Public Health ; 82(1): 37, 2024 Mar 18.
Article in English | MEDLINE | ID: mdl-38500190

ABSTRACT

BACKGROUND: Potentially inappropriate prescribing is common among older adults with multimorbidity due to various reasons, from concurrent application of multiple single-disease clinical guidelines to fragmentation of care. Interventions such as medication review have been implemented worldwide to reduce inappropriate prescribing for older adults. However, the implementability of such interventions are underexplored in the outpatient clinics in Singapore's public hospitals. Hence, the Pro-M study aims to assess the feasibility of implementing a physician-pharmacist collaborative care intervention in geriatric medicine outpatient clinics to facilitate appropriate prescribing for older adults in Singapore. METHODS: This is a single-arm, non-randomised feasibility study using a pre-post evaluation design. This study consists of two parts: (1) implementation phase of the intervention (6 months) and an (2) evaluation phase (3 months). Eligible patients will be recruited from geriatric medicine outpatient clinics at two public hospitals in Singapore through convenience sampling. The main components of the Pro-M intervention are: (1) pharmacist-facilitated medication reviews with feedback on any medication issues and potential recommendations to physicians, and (2) physicians communicating changes to other relevant prescribers. The evaluation phase will involve surveying and interviewing physicians and pharmacists involved in the implementation of the intervention. A mixed-method approach will be employed for data collection and analysis. The quantitative and qualitative findings will be triangulated and reported using Proctor's implementation outcomes: appropriateness, penetration, acceptability, fidelity, feasibility, and sustainability. A basic cost analysis will be conducted alongside the study. DISCUSSION: This is a phase 2 study to test the feasibility of implementing an intervention that was co-created with stakeholders during phase 1 development of an intervention to optimise prescribing for older adults with multimorbidity. The implementation will be assessed using Proctor's implementation outcomes to provide insights on the process and the feasibility of implementing medication reviews for older adults with multimorbidity as a routine practice in outpatient clinics. Data collected from this study will inform a subsequent scale-up study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05756478. Registered on 06 March 2023.

6.
Cancer ; 130(10): 1758-1765, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38422026

ABSTRACT

BACKGROUND: In early-stage non-small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for recurrence after curative intent therapy. This study aimed to risk stratify patients with early-stage NSCLC via a personalized, tumor-informed multiplex polymerase chain reaction (mPCR) next-generation sequencing assay. METHODS: This retrospective cohort study included patients with stage I-III NSCLC. Recruited patients received standard-of-care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole-exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient-specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single-nucleotide variants in plasma samples. RESULTS: The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence-free survival (RFS; hazard ratio [HR], 3.54; 95% confidence interval [CI], 1.00-12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0-12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63-158.9; p < .0001). CONCLUSIONS: ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early-stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Circulating Tumor DNA , High-Throughput Nucleotide Sequencing , Lung Neoplasms , Neoplasm Recurrence, Local , Neoplasm Staging , Neoplasm, Residual , Humans , Lung Neoplasms/genetics , Lung Neoplasms/blood , Lung Neoplasms/pathology , Male , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Female , Middle Aged , Aged , Retrospective Studies , Neoplasm Recurrence, Local/genetics , Neoplasm Recurrence, Local/diagnosis , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/blood , Carcinoma, Non-Small-Cell Lung/pathology , High-Throughput Nucleotide Sequencing/methods , Neoplasm, Residual/genetics , Neoplasm, Residual/diagnosis , Early Detection of Cancer/methods , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Adult , Aged, 80 and over , Multiplex Polymerase Chain Reaction/methods
7.
Protein Sci ; 33(3): e4904, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38358126

ABSTRACT

UBE2T is an attractive target for drug development due to its linkage with several types of cancers. However, the druggability of ubiquitin-conjugating E2 (UBE2T) is low because of the lack of a deep and hydrophobic pocket capable of forming strong binding interactions with drug-like small molecules. Here, we performed fragment screening using 19 F-nuclear magnetic resonance (NMR) and validated the hits with 1 H-15 N-heteronuclear single quantum coherence (HSQC) experiment and X-ray crystallographic studies. The cocrystal structures obtained revealed the binding modes of the hit fragments and allowed for the characterization of the fragment-binding sites. Further screening of structural analogues resulted in the identification of a compound series with inhibitory effect on UBE2T activity. Our current study has identified two new binding pockets in UBE2T, which will be useful for the development of small molecules to regulate the function of this protein. In addition, the compounds identified in this study can serve as chemical starting points for the development of UBE2T modulators.


Subject(s)
Ubiquitin-Conjugating Enzymes , Ubiquitin , Ubiquitin-Conjugating Enzymes/metabolism , Binding Sites
8.
Phytomedicine ; 124: 155301, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38181531

ABSTRACT

BACKGROUND: Despite the notable pharmacological potential of natural ginsenosides, their industrial application is hindered by low oral bioavailability. Recent research centers on the production of less-glycosylated minor ginsenosides. PURPOSE: This study aimed to explore the effect of a biologically synthesized ginsenoside CK-rich minor ginsenoside complex (AceCK40), on ameliorating colitis using DSS-induced colitis models in vitro and in vivo. METHODS: The ginsenoside composition of AceCK40 was determined by HPLC-ELSD and UHPLC-MS/MS analyses. In vitro colitis model was established using dextran sodium sulfate (DSS)-induced Caco-2 intestinal epithelial model. For in vivo experiments, DSS-induced severe colitis mouse model was established. RESULTS: In DSS-stimulated Caco-2 cells, AceCK40 downregulated mitogen-activated protein kinase (MAPK) activation (p < 0.05), inhibited monocyte chemoattractant protein-1 (MCP-1) production (p < 0.05), and enhanced MUC2 expression (p < 0.05), mediated via signaling pathway regulation. Daily AceCK40 administration at doses of 10 and 30 mg/kg/day was well tolerated by DSS-induced severe colitis mice. These doses led to significant alleviation of disease activity index score (> 36.0% decrease, p < 0.05), increased luminal immunoglobulin (Ig)G (> 37.6% increase, p < 0.001) and IgA (> 33.8% increase, p < 0.001), lowered interleukin (IL)-6 (> 65.7% decrease, p < 0.01) and MCP-1 (> 116.2% decrease, p < 0.05), as well as elevated serum IgA (> 51.4% increase, p < 0.001) and lowered serum IL-6 (112.3% decrease at 30 mg/kg, p < 0.001). Hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining revealed that DSS-mediated thickening of the muscular externa, extensive submucosal edema, crypt distortion, and decreased mucin droplets were significantly alleviated by AceCK40 administration. Additionally, daily administration of AceCK40 led to significant recovery of colonic tight junctions damaged by DSS through the elevation in the expression of adhesion molecules, including occludin, E-cadherin, and N-cadherin. CONCLUSION: This study presents the initial evidence elucidating the anti-colitis effects of AceCK40 and its underlying mechanism of action through sequential in vitro and in vivo systems employing DSS stimulation. Our findings provide valuable fundamental data for the utilization of AceCK40 in the development of novel anti-colitis candidates.


Subject(s)
Colitis , Ginsenosides , Humans , Mice , Animals , Ginsenosides/metabolism , Caco-2 Cells , Mice, Inbred C57BL , Tandem Mass Spectrometry , Colitis/chemically induced , Colitis/drug therapy , Colitis/metabolism , Colon , Immunoglobulin A/metabolism , Immunoglobulin A/pharmacology , Immunoglobulin A/therapeutic use , Dextran Sulfate/adverse effects , Disease Models, Animal , Intestinal Mucosa/metabolism
9.
Orbit ; 43(2): 203-207, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37772931

ABSTRACT

PURPOSE: To evaluate the prevalence and pattern of extraocular muscle enlargement and proptosis in patients with carotid cavernous fistulas (CCF). METHODS: We conducted a retrospective study on patients with digital subtraction angiography (DSA) confirmed CCFs with neuroimaging (computed tomography or magnetic resonance imaging) performed prior to the DSA. The maximum extraocular muscle diameters were recorded. Extraocular muscles were considered enlarged if they were greater than two standard deviations above the normal muscle diameters. Proptosis was defined as the distance between the interzygomatic line to the anterior globe of ≥2 mm compared to the contralateral orbit or ≥21 mm. RESULTS: Forty orbits from 20 patients were included. The mean age of participants was 65 ± 15 years and 13 (65%) were female. Thirteen (65%) fistulas were indirect and seven (35%) were direct. There was enlargement of at least one muscle in 11 (27.5%) orbits, and this was not correlated with the type of fistula (direct/indirect). The inferior rectus was most commonly enlarged in seven orbits (17.5%), followed by the medial rectus in five orbits (12.5%). Proptosis was found in 17 (43%) orbits and was more common ipsilateral to the fistula (58% ipsilateral group vs 19% contralateral group, p < .01). CONCLUSION: Extraocular muscle enlargement was observed in over one-fourth of CCFs. When enlarged, the inferior and medial rectus muscles are most commonly involved. These findings may help clinicians and radiologists when evaluating the CT or MRI scans of patients with suspected CCFs.


Subject(s)
Carotid-Cavernous Sinus Fistula , Exophthalmos , Humans , Female , Middle Aged , Aged , Aged, 80 and over , Male , Oculomotor Muscles/diagnostic imaging , Oculomotor Muscles/pathology , Retrospective Studies , Carotid-Cavernous Sinus Fistula/diagnostic imaging , Carotid-Cavernous Sinus Fistula/therapy , Exophthalmos/diagnostic imaging , Exophthalmos/etiology , Orbit , Hypertrophy/pathology
10.
J Pediatr Pharmacol Ther ; 28(5): 430-438, 2023.
Article in English | MEDLINE | ID: mdl-38130493

ABSTRACT

OBJECTIVES: Vancomycin 24-hour area under the curve over minimum inhibitory concentration (AUC/MIC) monitoring has been recommended over trough-based monitoring in pediatric patients. This study compared the proportion of target attainment between vancomycin AUC/MIC and trough-based methods, and identified risk factors for subtherapeutic initial extrapolated targets. METHODS: This was a retrospective, observational study conducted at KK Women's and Children's Hospital (KKH), Singapore. Patients aged 1 month to 18 years with stable renal function who received intravenous vancomycin between January 2014 and October 2017, with at least 2 vancomycin serum concentrations obtained after the first dose of vancomycin, were included. Using a pharmacokinetic software, namely Adult and Pediatric Kinetics (APK), initial extrapolated steady-state troughs and 24-hour AUC were determined by using a one-compartmental model. Statistical tests included Wilcoxon rank sum test, McNemar test, logistic regression, and classification and regression tree (CART) analysis. RESULTS: Of the 82 pediatric patients included, a significantly larger proportion of patients achieved therapeutic targets when the AUC/MIC-based method (24, 29.3%) was used than with the trough-based method (9, 11.0%; p < 0.01). Patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 or with age <13 years had an increased risk of obtaining subtherapeutic targets. However, empiric vancomycin doses of 60 mg/kg/day would be sufficient to achieve serum therapeutic targets, using the AUC/MIC-based method. CONCLUSION: The AUC/MIC-based vancomycin monitoring may be preferred because a larger proportion of patients could achieve initial therapeutic targets. Future prospective studies with larger sample size will be required to determine the optimal vancomycin strategy for pediatric patients.

11.
J AAPOS ; 27(6): 359-363, 2023 12.
Article in English | MEDLINE | ID: mdl-37931836

ABSTRACT

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare, autosomal recessive inherited disorder caused by mutations in ROBO3 gene. The clinical features of HGPPS include horizontal gaze palsy, progressive scoliosis, other oculomotor abnormalities such as strabismus and nystagmus. Whole-exome sequencing (WES) is used to diagnose rare Mendelian disorders, when routine standard tests have failed to make a formal pathological diagnosis. However, WES may identify variants of uncertain significance (VUS) that may add further ambiguity to the diagnosis. We report the case of a 4-year-old boy with horizontal gaze palsy, progressive scoliosis, microcephaly, and mild developmental delay. WES identified an intronic VUS in ROBO3 gene. We performed minigene splicing functional analysis to confirm the pathogenicity of this VUS. This report illustrates that WES data analysis with supportive functional analysis provides an effective approach to improve the diagnostic yield for unsolved clinical cases. This case also highlights the phenotypic heterogeneity in patients with HGPPS.


Subject(s)
Ocular Motility Disorders , Ophthalmoplegia, Chronic Progressive External , Scoliosis , Child, Preschool , Humans , Male , Mutation , Ocular Motility Disorders/diagnosis , Ocular Motility Disorders/genetics , Ocular Motility Disorders/complications , Ophthalmoplegia, Chronic Progressive External/diagnosis , Ophthalmoplegia, Chronic Progressive External/genetics , Receptors, Cell Surface/genetics , Receptors, Immunologic/genetics , Roundabout Proteins , Scoliosis/diagnosis , Scoliosis/genetics , Scoliosis/complications
12.
JAMA ; 330(20): 1961-1970, 2023 11 28.
Article in English | MEDLINE | ID: mdl-38015220

ABSTRACT

Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Agents , Cisplatin , Gemcitabine , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Adult , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Cisplatin/administration & dosage , Cisplatin/adverse effects , Cisplatin/therapeutic use , Double-Blind Method , Gemcitabine/administration & dosage , Gemcitabine/adverse effects , Gemcitabine/therapeutic use , Nasopharyngeal Carcinoma/drug therapy , Nasopharyngeal Carcinoma/mortality , Nasopharyngeal Carcinoma/pathology , Nasopharyngeal Carcinoma/secondary , Nasopharyngeal Neoplasms/drug therapy , Nasopharyngeal Neoplasms/mortality , Nasopharyngeal Neoplasms/pathology , Nasopharyngeal Neoplasms/secondary , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/mortality , Neoplasm Recurrence, Local/pathology , United States , Internationality
13.
Commun Biol ; 6(1): 949, 2023 09 18.
Article in English | MEDLINE | ID: mdl-37723198

ABSTRACT

Pediatric patients with recurrent and refractory cancers are in most need for new treatments. This study developed patient-derived-xenograft (PDX) models within the European MAPPYACTS cancer precision medicine trial (NCT02613962). To date, 131 PDX models were established following heterotopical and/or orthotopical implantation in immunocompromised mice: 76 sarcomas, 25 other solid tumors, 12 central nervous system tumors, 15 acute leukemias, and 3 lymphomas. PDX establishment rate was 43%. Histology, whole exome and RNA sequencing revealed a high concordance with the primary patient's tumor profile, human leukocyte-antigen characteristics and specific metabolic pathway signatures. A detailed patient molecular characterization, including specific mutations prioritized in the clinical molecular tumor boards are provided. Ninety models were shared with the IMI2 ITCC Pediatric Preclinical Proof-of-concept Platform (IMI2 ITCC-P4) for further exploitation. This PDX biobank of unique recurrent childhood cancers provides an essential support for basic and translational research and treatments development in advanced pediatric malignancies.


Subject(s)
Leukemia , Neoplasms , Animals , Child , Humans , Mice , Biological Specimen Banks , Disease Models, Animal , Heterografts , Neoplasms/genetics , Precision Medicine , Clinical Trials as Topic
14.
JAMA Netw Open ; 6(9): e2334936, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37738050

ABSTRACT

Importance: During COVID-19, Singapore simultaneously experienced a dengue outbreak, and acute hospitals were under pressure to lower bed occupancy rates. This led to new models of care to treat patients with acute, low-severity medical conditions either at home, in a hospital-at-home (HaH) model, or in a clinic-style setting sited at the emergency department in an ambulatory care team (ACT) model, but a reliable cost analysis for these models is lacking. Objective: To compare personnel costs of HaH and ACT with inpatient care. Design, Setting, and Participants: In this economic evaluation study, time-driven activity-based costing was used to compare the personnel cost of inpatient care with treating dengue via HaH and treating chest pain via ACT. Participants were patients with nonsevere dengue and chest pain unrelated to a coronary event admitted via the emergency department to the internal medicine service of a tertiary hospital in Singapore. Exposures: HaH for dengue and ACT for chest pain. Main Outcomes and Measures: A process map was created for the patient journey for a typical patient with each condition. The amount of time personnel spent on delivering care was estimated and the cost per minute determined based on their wages in 2022. The total cost of care was calculated by multiplying the time spent by the per-minute cost of the personnel resource and summing all costs. Results: Compared with inpatient care, HaH used 50% less nursing time (418 minutes, 95% uncertainty interval [UI], 370 to 465 minutes) but 80% more medical time (303 minutes, 95% UI, 270 to 338 minutes) per case of dengue. If implemented nationally, HaH would save an estimated 56 828 SGD per year (95% UI, -169 497 to 281 412 SGD [US $41 856; 95% UI, -$124 839 to $207 268]). The probability that HaH is cost saving was 69.2%. Compared with inpatient care, ACT used 15% less nursing time (296 minutes, 95% UI, 257 to 335 minutes) and 50% less medical time (57 minutes, 95% UI, 46 to 69 minutes) per case of chest pain. If implemented nationally, ACT would save an estimated 1 561 185 SGD per year (95% UI, 1 040 666 to 2 086 518 SGD [US $1 149 862; 95% UI, $766 483 to $1 536 786]). The probability that ACT is cost saving was 100%. Conclusions and Relevance: This economic evaluation found that the HaH and ACT models decreased the overall personnel cost of care. Reorganizing hospital resources may help hospitals reap the benefits of reduced hospital-acquired infections, improved patient recovery, and reduced hospital bed occupancy rates.


Subject(s)
COVID-19 , Dengue , Humans , Cost-Benefit Analysis , COVID-19/epidemiology , COVID-19/therapy , Tertiary Care Centers , Chest Pain , Dengue/epidemiology , Dengue/therapy
15.
Biomol NMR Assign ; 17(2): 269-274, 2023 12.
Article in English | MEDLINE | ID: mdl-37773242

ABSTRACT

Ubiquitin-conjugating enzyme E2 T (UBE2T) plays important roles in ubiquitination of proteins through participation in transferring ubiquitin to its substrate. Due to its importance in protein modifications, UBE2T associates with diverse diseases and serves as an important target for drug discovery and development. The crystal structure of UBE2T has been determined and the structure reveals the lack of a druggable pocket for binding to small molecules for clinical applications. Despite the challenge, effort has been made to develop UBE2T inhibitors. We obtained UBE2T constructs with and without the C-terminal region which is flexible in solution. Herein, we report the backbone resonance assignments for human UBE2T without the C-terminal region. The backbone dynamics of UBE2T was also explored. The available assignments will be helpful for hit identification, determining ligand binding site and understanding the mechanism of action of UBE2T inhibitors.


Subject(s)
Ubiquitin-Conjugating Enzymes , Ubiquitin , Humans , Nuclear Magnetic Resonance, Biomolecular , Ubiquitination , Ubiquitin/metabolism
16.
Br J Haematol ; 202(6): 1199-1204, 2023 09.
Article in English | MEDLINE | ID: mdl-37455143

ABSTRACT

Ferric carboxymaltose (FCM) administration helps reduce transfusion requirements in the perioperative situation, which improves patient outcomes and reduces healthcare costs. However, there is increasing evidence of hypophosphataemia after FCM use. We aim to determine the incidence of hypophosphataemia after FCM administration and elucidate potential biochemical factors associated with the development of subsequent hypophosphataemia. A retrospective review of anonymised data of all FCM administrations in a single institution was conducted from August 2018 to August 2021. Each unique FCM dose administered was examined to assess its effect on Hb and serum phosphate levels within the subsequent 28 days from each FCM administration. Phosphate levels were repeatedly measured within the 28-day interval and the lowest phosphate level within that period was determined. Patients' serum phosphate levels within 28 days of FCM administration were compared against normal serum phosphate levels within 2 weeks before FCM administration. The odds ratios of various pre-FCM serum markers were calculated to elucidate potential biochemical predictors of post-FCM hypophosphataemia. In 3 years, a total of 1296 doses of FCM were administered to 1069 patients. The mean improvement in Hb was 2.45 g/dL (SD = 1.94) within 28 days of FCM administration, with the mean time taken to peak Hb levels being 6.3 days (SD = 8.63), which is earlier than expected, but was observed in this study and hence reported. The incidence of hypophosphataemia <0.8 mmol/L was 22.7% (n = 186), and <0.4 mmol/L was 1.6% (n = 9). This figure is lower than the numbers reported in previously published meta-analyses given that routine checks of serum phosphate levels were not conducted initially and hence could possibly be higher. The odds of developing hypophosphataemia (<0.8 mmol/L) were 27.7 (CI: 17.3-44.2, p < 0.0001) if baseline serum phosphate was less than 1 mmol/L. The odds of developing hypophosphataemia (<0.8 mmol/L) were 1.3 (CI: 1.08-1.59, p < 0.01) if the change in Hb levels observed after FCM administration were more than 4 g/dL. Hypophosphataemia after FCM administration is significant and FCM should be used by clinicians with caution.


Subject(s)
Anemia, Iron-Deficiency , Hypophosphatemia , Humans , Incidence , Singapore/epidemiology , Ferric Compounds/adverse effects , Hypophosphatemia/chemically induced , Hypophosphatemia/epidemiology , Phosphates/adverse effects
17.
Cureus ; 15(6): e40449, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37456373

ABSTRACT

Background Over the past decade, telemedicine has experienced significant growth due to technological advancement, and the coronavirus disease 2019 (COVID-19) pandemic further accelerated its adoption. However, the field of anesthesiology has been slow in integrating and embracing telemedicine compared to other medical specialties. Methods We conducted an observational pilot feasibility study at a tertiary hospital in Singapore to assess the viability of a telemedicine hybrid protocol for preoperative anesthetic assessment. The study included patients aged 21 to 65 years, classified as American Society of Anesthesiology (ASA) physical status class 1 or 2, with a body mass index (BMI) below 35 kg/m2, who were capable of managing video conferencing. The patients selected were scheduled for low-risk surgeries. The primary objective was to evaluate the medical and technical feasibility of our telemedicine hybrid protocol, while the secondary objectives included assessing patient satisfaction and obtaining feedback from relevant stakeholders. Results From November 2021 to April 2022, a total of 116 patients were recruited, with 96 patients completing the study. No technical difficulties, surgical case cancellations, or incidents of unanticipated difficult airways were reported. The majority of survey respondents (88%) expressed satisfaction with the video consultation and indicated a preference for it over physical consultations for future preoperative anesthesia evaluations. Conclusion Based on our findings, a telemedicine hybrid protocol for preoperative anesthetic assessment demonstrated both technical and medical feasibility while yielding high patient satisfaction. Future research could focus on expanding the protocol to encompass more complex surgeries and include patients with higher ASA status.

18.
J Med Internet Res ; 25: e42789, 2023 Mar 07.
Article in English | MEDLINE | ID: mdl-36881455

ABSTRACT

BACKGROUND: Strategies to improve the selection of appropriate target journals may reduce delays in disseminating research results. Machine learning is increasingly used in content-based recommender algorithms to guide journal submissions for academic articles. OBJECTIVE: We sought to evaluate the performance of open-source artificial intelligence to predict the impact factor or Eigenfactor score tertile using academic article abstracts. METHODS: PubMed-indexed articles published between 2016 and 2021 were identified with the Medical Subject Headings (MeSH) terms "ophthalmology," "radiology," and "neurology." Journals, titles, abstracts, author lists, and MeSH terms were collected. Journal impact factor and Eigenfactor scores were sourced from the 2020 Clarivate Journal Citation Report. The journals included in the study were allocated percentile ranks based on impact factor and Eigenfactor scores, compared with other journals that released publications in the same year. All abstracts were preprocessed, which included the removal of the abstract structure, and combined with titles, authors, and MeSH terms as a single input. The input data underwent preprocessing with the inbuilt ktrain Bidirectional Encoder Representations from Transformers (BERT) preprocessing library before analysis with BERT. Before use for logistic regression and XGBoost models, the input data underwent punctuation removal, negation detection, stemming, and conversion into a term frequency-inverse document frequency array. Following this preprocessing, data were randomly split into training and testing data sets with a 3:1 train:test ratio. Models were developed to predict whether a given article would be published in a first, second, or third tertile journal (0-33rd centile, 34th-66th centile, or 67th-100th centile), as ranked either by impact factor or Eigenfactor score. BERT, XGBoost, and logistic regression models were developed on the training data set before evaluation on the hold-out test data set. The primary outcome was overall classification accuracy for the best-performing model in the prediction of accepting journal impact factor tertile. RESULTS: There were 10,813 articles from 382 unique journals. The median impact factor and Eigenfactor score were 2.117 (IQR 1.102-2.622) and 0.00247 (IQR 0.00105-0.03), respectively. The BERT model achieved the highest impact factor tertile classification accuracy of 75.0%, followed by an accuracy of 71.6% for XGBoost and 65.4% for logistic regression. Similarly, BERT achieved the highest Eigenfactor score tertile classification accuracy of 73.6%, followed by an accuracy of 71.8% for XGBoost and 65.3% for logistic regression. CONCLUSIONS: Open-source artificial intelligence can predict the impact factor and Eigenfactor score of accepting peer-reviewed journals. Further studies are required to examine the effect on publication success and the time-to-publication of such recommender systems.

20.
Oncologist ; 28(4): e198-e204, 2023 04 06.
Article in English | MEDLINE | ID: mdl-36779537

ABSTRACT

INTRODUCTION: In the National University Cancer Institute, Singapore (NCIS), 2 pilot programs providing (i) surgical prehabilitation before cancer surgery and (ii) geriatric oncology support for older adults planned for chemotherapy and/or radiotherapy were merged to form the Geriatric Oncology Longitudinal End to eNd (GOLDEN) program in 2019 to support patients from the time of their cancer diagnosis, through their treatment process, to cancer survivorship. METHODS AND MATERIALS: Older adults aged ≥65 years were enrolled in either surgical prehabilitation, the geriatric medical oncology (GO) arm, or both. All patients undergo a geriatric assessment. We assessed if patients had a change in treatment plans based on GOLDEN recommendations, and the impact on patient related outcomes. RESULTS: There were 777 patients enrolled in the GOLDEN program over 2 years; 569 (73%) were enrolled in surgical prehabilitation, 308 (40%) were enrolled in the GO arm, with 100 (12.8%) enrolled in both. 56.9% were females. Median age was 73. Lower gastrointestinal (51.2%) and hepatobiliary cancers (24.1%) were the most common cancer types. 43.4% were pre-frail and 11.7% were frail. Of the 308 patients in the GO arm, 86.0% had geriatric syndromes, while 60.7% had a change in their treatment plans based on GOLDEN recommendations. 31.5% reported an improved global health status, while 38.3% maintained their global health status. 226 (73%) responded that they had benefited from the GOLDEN. CONCLUSION: More than half of the population was either pre-frail or frail. Amongst those in the GO arm, the majority had geriatric syndromes and had a change in their treatment plans based on GOLDEN recommendations. Majority reported either improvement or maintenance in global health status, with most feeling they have benefited from the program. Further evaluation of the longitudinal geriatric hematology-oncology program for cancer-related outcomes and sustainability should be carried out.


Subject(s)
Neoplasms , Aged , Female , Humans , Male , Singapore , Feasibility Studies , Syndrome , Neoplasms/epidemiology , Neoplasms/surgery , Medical Oncology , Geriatric Assessment
SELECTION OF CITATIONS
SEARCH DETAIL
...