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1.
BMC Nephrol ; 23(1): 406, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36539703

RESUMEN

BACKGROUND: Introducing a de-novo home haemodialysis (HHD) program often raises safety concerns as errors could potentially lead to serious adverse events. Despite the complexity of performing haemodialysis at home without the supervision of healthcare staff, HHD has a good safety record. We aim to pre-emptively identify and reduce the risks to our new HHD program by risk assessment and using failure mode and effects analysis (FMEA) to identify potential defects in the design and planning of HHD. METHODS: We performed a general risk assessment of failure during transitioning from in-centre to HHD with a failure mode and effects analysis focused on the highest areas of failure. We collaborated with key team members from a well-established HHD program and one HHD patient. Risk assessment was conducted separately and then through video conference meetings for joint deliberation. We listed all key processes, sub-processes, step and then identified failure mode by scoring based on risk priority numbers. Solutions were then designed to eliminate and mitigate risk. RESULTS: Transitioning to HHD was found to have the highest risk of failure with 3 main processes and 34 steps. We identified a total of 59 areas with potential failures. The median and mean risk priority number (RPN) scores from failure mode effect analysis were 5 and 38, with the highest RPN related to vascular access at 256. As many failure modes with high RPN scores were related to vascular access, we focussed on FMEA by identifying the risk mitigation strategies and possible solutions in all 9 areas in access-related medical emergencies in a bundled- approach. We discussed, the risk reduction areas of setting up HHD and how to address incidents that occurred and those not preventable. CONCLUSIONS: We developed a safety framework for a de-novo HHD program by performing FMEA in high-risk areas. The involvement of two teams with different clinical experience for HHD allowed us to successfully pre-emptively identify risks and develop solutions.


Asunto(s)
Análisis de Modo y Efecto de Fallas en la Atención de la Salud , Humanos , Hemodiálisis en el Domicilio/efectos adversos , Medición de Riesgo , Factores de Riesgo
2.
Clin Infect Dis ; 73(9): e3136-e3143, 2021 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-33179039

RESUMEN

Singapore's hospitals had prepared to receive patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), planning various scenarios and levels of surge with a policy of isolating all confirmed cases as inpatients. The National University Hospital adopted a whole of hospital approach to coronavirus disease 2019 (COVID-19) with 3 primary goals: zero hospital-acquired COVID-19, all patients receive timely necessary care, and maintenance of staff morale. These goals to date have been met. A large influx of COVID-19 cases required significant transformation of clinical and operational processes. Isolation room numbers almost tripled and dedicated COVID-19 cohort wards were established, elective care was postponed, and intensive care units were augmented with equipment and manpower. In the wake of the surge, establishing a new normal for hospital care requires maintaining vigilance to detect endemic COVID-19, establishing contingency plans to ramp up in case of another surge, while returning to business as usual.


Asunto(s)
COVID-19 , Hospitales Universitarios , Humanos , Pacientes Internos , Unidades de Cuidados Intensivos , SARS-CoV-2
3.
Emerg Infect Dis ; 27(6): 1714-1717, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34013870

RESUMEN

We investigated an autochthonous case of cutaneous leishmaniasis caused by a genetically different Leishmania sp. in a patient in Arizona, USA. This parasite was classified into the subgenus Leishmania on the basis of multilocus DNA sequence and phylogenetic analyses of the rRNA locus and 11 reference genes.


Asunto(s)
Leishmania , Leishmaniasis Cutánea , Arizona , Humanos , Filogenia
4.
BMC Med ; 18(1): 179, 2020 06 08.
Artículo en Inglés | MEDLINE | ID: mdl-32507112

RESUMEN

BACKGROUND: On January 30, COVID-19 was declared a Public Health Emergency of International Concern-a week after Singapore's first imported case and 5 days before local transmission. The National University Hospital (NUH) is Singapore's third largest hospital with 1200 beds, heavy clinical workloads, and major roles in research and teaching. MAIN BODY: With memories of SARS still vivid, there was an urgent requirement for the NUH Division of Infectious Diseases to adapt-undergoing major reorganization to face rapidly changing priorities while ensuring usual essential services and standards. Leveraging on individual strengths, our division mobilized to meet the demands of COVID-19 while engaging in high-level coordination, strategy, and advocacy. We present our experience of the 60 days since the nation's first case. During this time, our hospital has managed 3030 suspect cases, including 1300 inpatients, 37 confirmed cases, and overseen 4384 samples tested for COVID-19. CONCLUSION: Complex hospital adaptations were supported by an unprecedented number of workflows and coordination channels essential to safe and effective operations. The actions we describe, aligned with international recommendations and emerging evidence-based best practices, may serve as a framework for other divisions and institutions facing the spread of COVID-19 globally.


Asunto(s)
Infecciones por Coronavirus , Hospitales Universitarios , Innovación Organizacional , Pandemias , Neumonía Viral , Salud Pública , Centros Médicos Académicos , Betacoronavirus , COVID-19 , Enfermedades Transmisibles , Infecciones por Coronavirus/epidemiología , Atención a la Salud , Hospitales Universitarios/organización & administración , Humanos , Neumonía Viral/epidemiología , SARS-CoV-2 , Singapur/epidemiología , Carga de Trabajo
5.
Sex Transm Dis ; 46(1): 9-17, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-29994936

RESUMEN

PURPOSE: Trichomoniasis is the most prevalent nonviral sexually transmitted infection (STI) in the United States. It can present with vaginitis in women and urethritis in men, but is most often asymptomatic or occurs with minimal symptoms. It is associated with other STIs, adverse pregnancy outcomes and pelvic inflammatory disease. For these reasons, health care provider awareness of trichomoniasis is of public health importance. METHODS: To assess practitioner knowledge, attitudes, and practices concerning trichomoniasis management, the American College of Obstetricians and Gynecologists conducted an online survey in 2016 of its members, and we analyzed results from 230 respondents. RESULTS: We note discrepancies between practice and recommendations among surveyed providers: a minority of respondents routinely screen human immunodeficiency virus (HIV)-positive patients for trichomoniasis (10.7%, "most of the time"; 95% confidence interval [CI], 6.7-15.8; 33.0%, "always"; 95% CI, 26.5%-40.0%), treat trichomoniasis in HIV-positive patients with the recommended dose of metronidazole 500 mg twice a day for 7 days (25.8%; 95% CI, 20.0%-32.3%), or retest patients diagnosed with trichomoniasis 3 months after treatment (9.6%; 95% CI, 6.1%-14.3%). Only 29.0% (95% CI, 23.0%-35.5%) retreat with metronidazole 500 mg twice a day for 7 days in patients who have failed prior treatment. CONCLUSIONS: Screening for and treatment of trichomoniasis in HIV-positive patients, and retesting and retreatment for trichomoniasis in the general population appear to be suboptimal. Continuing education for providers is needed for this common but "neglected" STI.


Asunto(s)
Conocimientos, Actitudes y Práctica en Salud , Médicos/estadística & datos numéricos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Tricomoniasis/diagnóstico , Antiprotozoarios/administración & dosificación , Educación Médica Continua , Femenino , Ginecología , Humanos , Masculino , Metronidazol/administración & dosificación , Persona de Mediana Edad , Obstetricia , Enfermedades de Transmisión Sexual/parasitología , Encuestas y Cuestionarios , Tricomoniasis/tratamiento farmacológico , Estados Unidos , Uretritis/parasitología , Vaginitis/parasitología
7.
Clin Infect Dis ; 66(2): 206-212, 2018 01 06.
Artículo en Inglés | MEDLINE | ID: mdl-29020386

RESUMEN

Background: Toxocariasis results from infection with larval stages of a dog and cat intestinal nematode and causes human morbidity. The current United States estimate of Toxocara exposure is 13.9% (National Health and Nutrition Examination Survey [NHANES] III [1988-1994]). Methods: We used a multiplex bead-based assay (Tc-CTL-1MBA) with purified Toxocara canis antigen to estimate Toxocara antibody seroprevalence in serum of 13 509 persons aged ≥6 years from NHANES 2011-2014 and identified seropositivity risk factors. We tested a subset of 500 samples with the T. canis enzyme immunoassay used in NHANES III to estimate prior seroprevalence had samples from NHANES III been tested by Tc-CTL-1MBA. Results: The age-standardized estimate of Toxocara seroprevalence was 5.0% (95% confidence interval [CI], 4.2%-5.8%), lower than previously reported even after adjusting for increased Tc-CTL-1MBA specificity. Risk factors for seropositivity from multiple logistic regression were older age, non-Hispanic black/Hispanic origin, male sex, living below poverty level, households with ≥0.5 persons per room, less than college education, and birth outside of the United States. Conclusions: Toxocara seroprevalence estimates in 2011-2014 were lower than in a study from NHANES III (1988-1994), but seropositivity risk factors remained the same and should continue to be the focus of prevention efforts.


Asunto(s)
Anticuerpos Antihelmínticos/sangre , Toxocariasis/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Niño , Estudios Transversales , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Estudios Seroepidemiológicos , Estados Unidos/epidemiología , Adulto Joven
8.
MMWR Morb Mortal Wkly Rep ; 67(30): 825-828, 2018 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-30070981

RESUMEN

Angiostrongyliasis is caused by infection and migration to the brain of larvae of the parasitic nematode Angiostrongylus cantonensis, or rat lungworm. Adult A. cantonensis reside in the lungs of the definitive wild rodent host, where they produce larvae passed in feces, which are then ingested by snails and slugs (gastropods). Human infection typically occurs when gastropods containing mature larvae are inadvertently ingested by humans. Although human infection often is asymptomatic or involves transient mild symptoms, larval migration to the brain can lead to eosinophilic meningitis, focal neurologic deficits, coma, and death. The majority of cases of human angiostrongyliasis occur in Asia and the Pacific Islands, including Hawaii, but autochthonous and imported cases have been reported in the continental United States (1,2), underscoring the importance of provider recognition to ensure prompt identification and treatment. The epidemiologic and clinical features of 12 angiostrongyliasis cases in the continental United States were analyzed. These cases were identified through A. cantonensis polymerase chain reaction (PCR) testing (3) of cerebrospinal fluid (CSF) submitted to CDC from within the continental United States. Six cases were likely a result of autochthonous transmission in the southern United States. All 12 patients had CSF pleocytosis and eosinophilia, consistent with eosinophilic meningitis. Health care providers need to be aware of the possibility of angiostrongyliasis in patients with eosinophilic meningitis, especially in residents in the southern United States or persons who have traveled outside the continental United States and have a history of ingestion of gastropods or contaminated raw vegetables.


Asunto(s)
Angiostrongylus cantonensis/aislamiento & purificación , Enfermedades del Sistema Nervioso Central/epidemiología , Infecciones por Strongylida/complicaciones , Infecciones por Strongylida/diagnóstico , Adolescente , Adulto , Anciano , Angiostrongylus cantonensis/genética , Animales , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Estados Unidos/epidemiología , Adulto Joven
10.
BMC Anesthesiol ; 18(1): 108, 2018 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-30111288

RESUMEN

BACKGROUND: Dental injury is a common perioperative complication, but there are no country specific data available, especially with the use of supraglottic airway devices (SAD). The aims of our study are to report the incidence, risk factors, and local practices in the management of perioperative dental injuries in Singapore. METHODS: We analyzed data from the departmental database from 2011 to 2014, noting the anticipated difficulty of airway instrumentation, intubation grade, pre-existing dental risk factors, location of dental trauma discovery, position of teeth injured and presence of dental referral. The risk factors for dental trauma were then identified using logistic regression (between 51 dental trauma patients and 55,107 patients without dental trauma). RESULTS: The rate of dental injury was 0.092% for general anaesthesia cases. The most significant patient risk factor is the presence of pre-existing dental risk factors (OR 12.55). Anaesthetic risk factors include McGrath MAC usage (OR 2.51) and a Cormack and Lehane grade of 3 or more (OR 7.25). Most of the dental injuries were discovered in the operating theatre. 7 (13.7%) patients had SAD inserted and only 23 (45.1%) cases were referred to dental services. CONCLUSION: Videolaryngoscopy with the McGrath MAC is associated with an increased likelihood of dental injury. This could be either because videolarygoscopes were used when increased risk of dental trauma was anticipated, or due to incorrect technique of laryngoscopy. Future studies should be done to establish the causality. The management of dental injuries could be improved with development of departmental guidelines.


Asunto(s)
Anestesia General/efectos adversos , Centros de Atención Terciaria/estadística & datos numéricos , Traumatismos de los Dientes/epidemiología , Humanos , Singapur/epidemiología
11.
J Anesth ; 30(3): 514-7, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-26825311

RESUMEN

Using three-dimensional printing, we produced adaptors to attach a smartphone with camera to the eyepiece of the Airtraq(®) laryngoscope. This low-cost system enabled a team to simultaneously view the laryngoscopy process on the smartphone screen, and also enabled image transmission. We compared the Airtraq(®) with the smartphone Airtraq(®) system in a crossover study of trainee anesthesiologists performing tracheal intubation in a manikin. We also evaluated the smartphone Airtraq(®) system for laryngoscopy and tracheal intubation in 30 patients, including image transmission to and communication with a remote instructor. In the manikin study, the smartphone Airtraq(®) system enabled instruction where both trainee and instructor could view the larynx simultaneously, and did not substantially increase the time required for intubation. In the patient study, we were able to view the larynx in all 30 patients, and the remote instructor was able to receive the images and to respond on correctness of laryngoscopy and tracheal tube placement. Tracheal intubation was successful within 90s in 19 (63 %) patients. In conclusion, use of a smartphone with the Airtraq(®) may facilitate instruction and communication of laryngoscopy with the Airtraq(®), overcoming some of its limitations.


Asunto(s)
Intubación Intratraqueal/métodos , Laringoscopios , Laringoscopía/métodos , Teléfono Inteligente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Diseño de Equipo , Humanos , Laringe , Maniquíes , Persona de Mediana Edad , Tráquea , Adulto Joven
12.
J Anesth ; 29(2): 295-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25238682

RESUMEN

The I-gel is a supraglottic airway device which is commonly used in adult patients undergoing general anesthesia. In this study, we evaluated the speed of insertion, adequacy of ventilation, leak pressure, gastric tube insertion, and problems when using the I-gel in children. We included 70 patients aged between 1 and 16 years old with ASA physical status classification I or II, undergoing elective surgery requiring general anesthesia, for which use of a supraglottic airway would be appropriate. The overall insertion success rate was 96 % with a median insertion time of 25 (18-34) [7-100] s. Seventeen patients (24.3 %) experienced problems including the need for change of airway device, laryngospasm, device displacement, blood on device after removal, and postoperative sore throat. In conclusion, there was a moderate rate of problems when using the I-gel in children, and it was necessary to change the airway in a few patients to optimize ventilation.


Asunto(s)
Manejo de la Vía Aérea/instrumentación , Anestesia General/métodos , Intubación Intratraqueal/instrumentación , Adolescente , Manejo de la Vía Aérea/efectos adversos , Anestesia General/efectos adversos , Niño , Preescolar , Femenino , Geles , Humanos , Lactante , Intubación Gastrointestinal , Intubación Intratraqueal/efectos adversos , Máscaras Laríngeas , Masculino , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/terapia , Respiración Artificial , Resultado del Tratamiento
14.
Clin Med Insights Cardiol ; 18: 11795468241249059, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38686315

RESUMEN

Pseudoaneurysm is a rare but fatal complication of myocardial infarction (MI). With the advances in cardiovascular disease detection and treatments, fatal structural complications post-MI are now rare. When they occur, advanced diagnostic modalities can be used for early diagnosis, aiding surgical planning, and improving prognosis. In our case, post-MI left ventricle pseudoaneurysm complicated by hemopericardium was diagnosed using cardiac computed tomography angiography (CCTA). Use of attenuation measurement on CCTA helped diagnose active extravasation into the hemopericardium. This case highlights the high index of suspicion needed for rare but fatal complications post-MI and the utility of CCTA in their management.

15.
Clin Infect Dis ; 55(12): 1661-8, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22972866

RESUMEN

BACKGROUND: Studies of Clostridium difficile outbreaks suggested that certain ribotypes (eg, 027 and 078) cause more severe disease than other ribotypes. A growing number of studies challenge the validity of this hypothesis. METHODS: We conducted a cross-sectional study of C. difficile infection (CDI) to test whether ribotype predicted clinical severity when adjusted for the influence of other predictors. Toxigenic C. difficile isolates were cultured from stool samples, screened for genes encoding virulence factors by polymerase chain reaction (PCR) and ribotyped using high-throughput, fluorescent PCR ribotyping. We collected data for 15 covariates (microbiologic, epidemiologic, and laboratory variables) and determined their individual and cumulative influence on the association between C. difficile ribotype and severe disease. We then validated this influence using an independent data set. RESULTS: A total of 34 severe CDI cases were identified among 310 independent cases of disease (11.0%). Eleven covariates, including C. difficile ribotype, were significant predictors of severe CDI in unadjusted analysis. However, the association between ribotypes 027 and 078 and severe CDI was not significant after adjustment for any of the other covariates. After full adjustment, severe cases were significantly predicted only by patients' white blood cell count and albumin level. This result was supported by analysis of a validation data set containing 433 independent CDI cases (45 severe cases; 10.4%). CONCLUSIONS: Ribotype is not a significant predictor of severe CDI when adjusted for the influence of any other variables separately or in combination. White blood cell count and albumin level are the most clinically relevant predictors of severe CDI cases.


Asunto(s)
Clostridioides difficile/clasificación , Enterocolitis Seudomembranosa/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Clostridioides difficile/genética , Clostridioides difficile/aislamiento & purificación , Clostridioides difficile/patogenicidad , Estudios Transversales , Enterocolitis Seudomembranosa/epidemiología , Femenino , Humanos , Lactante , Modelos Logísticos , Masculino , Michigan/epidemiología , Persona de Mediana Edad , Oportunidad Relativa , Reproducibilidad de los Resultados , Ribotipificación
16.
Am J Ophthalmol ; 237: 235-240, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34942108

RESUMEN

PURPOSE: To report outcomes of tape splint tarsorrhaphy (TST) for persistent corneal epithelial defects (PCED). DESIGN: Retrospective, interventional case series. METHODS: The study population was consecutive patients with a PCED (14 days or longer) treated at a tertiary cornea clinic with TST. Patients with a corneal epithelial defect that did not respond to treatment with a bandage contact lens were included. Patients with a follow-up time of less than 3 months were excluded. Time to PCED resolution was the main outcome measure. RESULTS: Thirty-four eyes of 33 patients (mean age 62.9 ± 17.8 years; range, 27-90 years) were included in this study. The main etiologies of the PCED were post keratoplasty (n = 15), herpes simplex virus (n = 4), superficial keratectomy (n = 3), neurotrophic cornea (n = 4), fungal keratitis (n = 2), exposure keratopathy (n = 2), failed graft (n = 1), peripheral ulcerative keratitis (n = 1), rosacea (n = 1), and stitch abscess (n = 1). Mean ± SD time from PCED presentation to TST was 58.9 ± 106.3 days (range, 14-390 days). The mean ± SD area of the PCED was 25.1 ± 15.7 mm2 (range, 0.50-42.0 mm2). After TST, resolution of the PCED was achieved in 29/34 eyes (85.3%) without the need for additional interventions within 22.5 ± 24.3 days (range, 2-105 days). The mean ± SD logMAR best-corrected visual acuity improved significantly from 1.11 ± 0.41 to 0.83 ± 0.70 (P = .02). There were no complications attributed to TST and 2 patients elected to discontinue due to discomfort. CONCLUSIONS: TST achieved resolution of PCEDs secondary to various etiologies in 85.3% of eyes, with significant improvement in vision demonstrated. This simple, inexpensive, noninvasive technique may be considered for patients with PCEDs.


Asunto(s)
Enfermedades de la Córnea , Trasplante de Córnea , Úlcera de la Córnea , Anciano , Anciano de 80 o más Años , Córnea/cirugía , Enfermedades de la Córnea/terapia , Trasplante de Córnea/efectos adversos , Úlcera de la Córnea/cirugía , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Férulas (Fijadores) , Resultado del Tratamiento
17.
Artículo en Inglés | MEDLINE | ID: mdl-36361096

RESUMEN

CONTEXT: Healthcare workers all over the world were prioritized for vaccination against COVID-19 in view of the high-risk nature of their job scopes when vaccines were first available in late 2020. Vaccine hesitancy was an important problem to tackle in order to achieve a high vaccination rate, especially for vaccines that were developed using mRNA technology. We aimed to use the '3Cs' model to address vaccine hesitancy to ensure maximal uptake of the Pfizer-BioNTech vaccine among healthcare workers in a tertiary hospital in Singapore. METHODS: Various measures were used to reduce the confidence, complacency, and convenience barriers. The staff vaccination clinic was on-site and centralized, with appointments given in advance to ensure vaccine availability and to reduce wait time, providing convenience to staff. Direct and repeated communications with the staff via multiple channels were used to address vaccine safety and efficacy so as to promote confidence in the vaccines and overcome complacency barriers. To further encourage staff to get vaccinated, staff were allowed time off for vaccination when at work. Staff with a high risk of exposure to COVID-19 or those caring for immunocompromised patients were prioritized to take the vaccines first. The collection of data on adverse events was via on-site monitoring and consultation at Occupational Health Clinic (OHC). RESULTS: Nearly 80% of staff had completed vaccination when the vaccination exercise ended at the end of March 2021. With the loosening of the contraindications to vaccination over time, staff vaccination rates reached 89.3% in early July and nearly 99.9% by the end of the year. No major or serious vaccine-related medication or administration errors were reported. No staff had anaphylaxis. CONCLUSIONS: By using the '3Cs' model to plan out the vaccination exercise, it is possible to achieve a high vaccination rate coupled with effective and customized communications. This multi-disciplinary team approach can be adapted to guide vaccination efforts in various settings in future pandemics.


Asunto(s)
COVID-19 , Gripe Humana , Servicios de Salud del Trabajador , Vacunas , Humanos , Vacunas contra la COVID-19/uso terapéutico , COVID-19/prevención & control , Centros de Atención Terciaria , Gripe Humana/prevención & control , Singapur/epidemiología , Vacunación
18.
Comput Methods Programs Biomed ; 221: 106839, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35550456

RESUMEN

BACKGROUND AND OBJECTIVE: Platinum-induced nephrotoxicity is a severe and unexpected adverse drug reaction that could lead to treatment failure in non-small cell lung cancer patients. Better prediction and management of this nephrotoxicity can increase patient survival. Our study aimed to build up and compare the best machine learning models with clinical and genomic features to predict platinum-induced nephrotoxicity in non-small cell lung cancer patients. METHODS: Clinical and genomic data of patients undergoing platinum chemotherapy at Wan Fang Hospital were collected after they were recruited. Twelve models were established by artificial neural network, logistic regression, random forest, and support vector machine with integrated, clinical, and genomic modes. Grid search and genetic algorithm were applied to construct the fine-tuned model with the best combination of predictive hyperparameters and features. Accuracy, precision, recall, F1 score, and area under the receiver operating characteristic curve were calculated to compare the performance of the 12 models. RESULTS: In total, 118 patients were recruited for this study, among which 28 (23.73%) were experiencing nephrotoxicity. Machine learning models with clinical and genomic features achieved better prediction performances than clinical or genomic features alone. Artificial neural network with clinical and genomic features demonstrated the best predictive outcomes among all 12 models. The average accuracy, precision, recall, F1 score and area under the receiver operating characteristic curve of the artificial neural network with integrated mode were 0.923, 0.950, 0.713, 0.808 and 0.900, respectively. CONCLUSIONS: Machine learning models with clinical and genomic features can be a preliminary tool for oncologists to predict platinum-induced nephrotoxicity and provide preventive strategies in advance.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Platino (Metal) , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Aprendizaje Automático , Platino (Metal)/toxicidad
19.
Cell Chem Biol ; 29(2): 249-258.e5, 2022 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-34547225

RESUMEN

Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates plasma low-density lipoprotein cholesterol (LDL-C) levels by promoting hepatic LDL receptor (LDLR) degradation. Therapeutic antibodies that disrupt PCSK9-LDLR binding reduce LDL-C concentrations and cardiovascular disease risk. The epidermal growth factor precursor homology domain A (EGF-A) of the LDLR serves as a primary contact with PCSK9 via a flat interface, presenting a challenge for identifying small molecule PCSK9-LDLR disruptors. We employ an affinity-based screen of 1013in vitro-translated macrocyclic peptides to identify high-affinity PCSK9 ligands that utilize a unique, induced-fit pocket and partially disrupt the PCSK9-LDLR interaction. Structure-based design led to molecules with enhanced function and pharmacokinetic properties (e.g., 13PCSK9i). In mice, 13PCSK9i reduces plasma cholesterol levels and increases hepatic LDLR density in a dose-dependent manner. 13PCSK9i functions by a unique, allosteric mechanism and is the smallest molecule identified to date with in vivo PCSK9-LDLR disruptor function.


Asunto(s)
Péptidos/farmacología , Proproteína Convertasa 9/metabolismo , Receptores de LDL/antagonistas & inhibidores , Animales , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Ligandos , Masculino , Ratones , Ratones Endogámicos C57BL , Péptidos/síntesis química , Péptidos/química , Conformación Proteica , Receptores de LDL/metabolismo
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