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1.
J Diabetes Sci Technol ; 18(3): 541-548, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38454631

RESUMO

BACKGROUND: Hyperglycemia occurs in 22% to 46% of hospitalized patients, negatively affecting patient outcomes, including mortality, inpatient complications, length of stay, and hospital costs. Achieving inpatient glycemic control is challenging due to inconsistent caloric intake, changes from home medications, a catabolic state in the setting of acute illness, consequences of acute inflammation, intercurrent infection, and limitations in labor-intensive glucose monitoring and insulin administration. METHOD: We conducted a retrospective cross-sectional analysis at the University of California San Francisco hospitals between September 3, 2020 and September 2, 2021, comparing point-of-care glucose measurements in patients on nil per os (NPO), continuous total parenteral nutrition, or continuous tube feeding assigned to our novel automated self-adjusting subcutaneous insulin algorithm (SQIA) or conventional, physician-driven insulin dosing. We also evaluated physician efficiency by tracking the number of insulin orders placed or modified. RESULTS: The proportion of glucose in range (70-180 mg/dL) was higher in the SQIA group than in the conventional group (71.0% vs 69.0%, P = .153). The SQIA led to a lower proportion of severe hyperglycemia (>250 mg/dL; 5.8% vs 7.2%, P = .017), hypoglycemia (54-69 mg/dL; 0.8% vs 1.2%, P = .029), and severe hypoglycemia (<54 mg/dL; 0.3% vs 0.5%, P = .076) events. The number of orders a physician had to place while a patient was on the SQIA was reduced by a factor of more than 12, when compared with while a patient was on conventional insulin dosing. CONCLUSIONS: The SQIA reduced severe hyperglycemia, hypoglycemia, and severe hypoglycemia compared with conventional insulin dosing. It also improved physician efficiency by reducing the number of order modifications a physician had to place.


Assuntos
Algoritmos , Glicemia , Controle Glicêmico , Hipoglicemiantes , Insulina , Humanos , Estudos Retrospectivos , Insulina/administração & dosagem , Insulina/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Glicemia/análise , Glicemia/efeitos dos fármacos , Estudos Transversais , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Controle Glicêmico/efeitos adversos , Controle Glicêmico/métodos , Idoso , Hiperglicemia/sangue , Hiperglicemia/tratamento farmacológico , Hospitalização , Injeções Subcutâneas , Hipoglicemia/induzido quimicamente , Hipoglicemia/prevenção & controle , Hipoglicemia/sangue , Hipoglicemia/epidemiologia
2.
Med Care ; 62(3): 189-195, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38180051

RESUMO

BACKGROUND: Studies of nurse staffing frequently use data aggregated at the hospital level that do not provide the appropriate context to inform unit-level decisions, such as nurse staffing. OBJECTIVES: Describe a method to link patient data collected during the provision of routine care and recorded in the electronic health record (EHR) to the nursing units where care occurred in a national dataset. RESEARCH DESIGN: We identified all Veterans Health Administration acute care hospitalizations in the calendar year 2019 nationwide. We linked patient-level EHR and bar code medication administration data to nursing units using a crosswalk. We divided hospitalizations into segments based on the patient's time-stamped location (ward stays). We calculated the number of ward stays and medication administrations linked to a nursing unit and the unit-level and facility-level mean patient risk scores. RESULTS: We extracted data on 1117 nursing units, 3782 EHR patient locations associated with 1,137,391 ward stays, and 67,772 bar code medication administration locations associated with 147,686,996 medication administrations across 125 Veterans Health Administration facilities. We linked 89.46% of ward stays and 93.10% of medication administrations to a nursing unit. The average (standard deviation) unit-level patient severity across all facilities is 4.71 (1.52), versus 4.53 (0.88) at the facility level. CONCLUSIONS: Identification of units is indispensable for using EHR data to understand unit-level phenomena in nursing research and can provide the context-specific information needed by managers making frontline decisions about staffing.


Assuntos
Pesquisa em Enfermagem , Recursos Humanos de Enfermagem Hospitalar , Humanos , Admissão e Escalonamento de Pessoal , Registros Eletrônicos de Saúde , Hospitais
3.
Personal Disord ; 14(1): 19-28, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36848070

RESUMO

The field of personality disorder research has grown since the publication of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition, in 1980; with a notable evolution in the way that personality disorders are defined and operationalized. In evaluating this research, it is necessary to consider the range of sampling practices used. The goal of this study was to describe current sampling methods in personality disorder research and provide recommendations to guide sample design in future personality disorder research. To do this, we coded sampling practices described in recent empirical articles published in four journals that showcase research on personality disorders. We summarized aspects of sampling design including the combination of study question and sample characteristics (e.g., sample size, sample source, and use of screening), study design, and demographic representation of samples. Findings reveal a need for studies to better consider whether their samples are fit for purpose and to make explicit their target population and sampling frame, as well as the specific procedures (i.e., recruitment) used to carry out sampling. We also discuss issues that arise when attempting to capture low-base rate pathology, which is often associated with high comorbidity. We emphasize a process-oriented approach to developing a sampling strategy for personality disorders research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Transtornos da Personalidade , Personalidade , Humanos , Transtornos da Personalidade/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Projetos de Pesquisa
4.
J Invest Dermatol ; 143(8): 1423-1429.e1, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36804150

RESUMO

Artificial intelligence algorithms to classify melanoma are dependent on their training data, which limits generalizability. The objective of this study was to compare the performance of an artificial intelligence model trained on a standard adult-predominant dermoscopic dataset before and after the addition of additional pediatric training images. The performances were compared using held-out adult and pediatric test sets of images. We trained two models: one (model A) on an adult-predominant dataset (37,662 images from the International Skin Imaging Collaboration) and the other (model A+P) on an additional 1,536 pediatric images. We compared performance between the two models on adult and pediatric held-out test images separately using the area under the receiver operating characteristic curve. We then used Gradient-weighted Class Activation Maps and background skin masking to understand the contributions of the lesion versus background skin to algorithm decision making. Adding images from a pediatric population with different epidemiological and visual patterns to current reference standard datasets improved algorithm performance on pediatric images without diminishing performance on adult images. This suggests a way that dermatologic artificial intelligence models can be made more generalizable. The presence of background skin was important to the pediatric-specific improvement seen between models. Our study highlights the importance of carefully curated and labeled data from diverse inputs to improve the generalizability of AI models for dermatology, in this case applied to dermoscopic images of adult and pediatric lesions to improve melanoma detection.


Assuntos
Melanoma , Dermatopatias , Neoplasias Cutâneas , Adulto , Humanos , Criança , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Inteligência Artificial , Melanoma/diagnóstico , Melanoma/patologia , Pele/patologia , Dermatopatias/patologia
5.
Cancer Med ; 12(1): 179-188, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35666021

RESUMO

BACKGROUND: Cutaneous metastases in pancreatic cancer (PC) are rare. Herein, we evaluate the clinical, genomic, and other descriptors of patients with PC and cutaneous metastases. METHODS: Institutional databases were queried, and clinical history, demographics, PC cutaneous metastasis details, and overall survival (OS) from cutaneous metastasis diagnosis were abstracted. OS was estimated using Kaplan-Meier methods. RESULTS: Forty patients were identified, and median age (Q1-Q3, IQR) of PC diagnosis was 66.0 (59.3-72.3, 12.9) years. Most patients had Stage IV disease at diagnosis (n = 26, 65%). The most common location of the primary tumor was the tail of the pancreas (n = 17, 43%). The most common cutaneous metastasis site was the abdomen (n = 31, 78%), with umbilical lesions occurring in 74% (n = 23) of abdominal lesions. The median OS (95% CI) was 11.4 months (7.0, 20.4). Twenty-three patients had umbilical metastases (58%), and 17 patients had non-umbilical metastases (43%). The median OS (95% CI) was 13.7 (7.0, 28.7) months in patients with umbilical metastases and 8.9 (4.1, Not reached) months in patients with non-umbilical metastases (p = 0.1). Sixteen of 40 (40%) patients underwent somatic testing, and findings were consistent with known profiles. Germline testing in 12 (30%) patients identified pathogenic variants in patients: CHEK2, BRCA1, and ATM. CONCLUSION: Cutaneous metastases from PC most frequently arise from a pancreas tail primary site and most frequently occur in the umbilicus. Cutaneous metastases may generally be categorized as umbilical or non-umbilical metastases.


Assuntos
Neoplasias Pancreáticas , Neoplasias Cutâneas , Idoso , Humanos , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Neoplasias Cutâneas/patologia , Umbigo/patologia , Pessoa de Meia-Idade , Neoplasias Pancreáticas
6.
Appl Clin Inform ; 14(1): 76-90, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36473498

RESUMO

OBJECTIVE: The aim of the study is to introduce an innovative use of bar code medication administration (BCMA) data, medication pass analysis, that allows for the examination of nurse staffing and workload using data generated during regular nursing workflow. METHODS: Using 1 year (October 1, 2014-September 30, 2015) of BCMA data for 11 acute care units in one Veterans Affairs Medical Center, we determined the peak time for scheduled medications and included medications scheduled for and administered within 2 hours of that time in analyses. We established for each staff member their daily peak-time medication pass characteristics (number of patients, number of peak-time scheduled medications, duration, start time), generated unit-level descriptive statistics, examined staffing trends, and estimated linear mixed-effects models of duration and start time. RESULTS: As the most frequent (39.7%) scheduled medication time, 9:00 was the peak-time medication pass; 98.3% of patients (87.3% of patient-days) had a 9:00 medication. Use of nursing roles and number of patients per staff varied across units and over time. Number of patients, number of medications, and unit-level factors explained significant variability in registered nurse (RN) medication pass duration (conditional R2 = 0.237; marginal R2 = 0.199; intraclass correlation = 0.05). On average, an RN and a licensed practical nurse (LPN) with four patients, each with six medications, would be expected to take 70 and 74 minutes, respectively, to complete the medication pass. On a unit with median 10 patients per LPN, the median duration (127 minutes) represents untimely medication administration on more than half of staff days. With each additional patient assigned to a nurse, average start time was earlier by 4.2 minutes for RNs and 1.4 minutes for LPNs. CONCLUSION: Medication pass analysis of BCMA data can provide health systems a means for assessing variations in staffing, workload, and nursing practice using data generated during routine patient care activities.


Assuntos
Recursos Humanos de Enfermagem Hospitalar , Carga de Trabalho , Humanos , Admissão e Escalonamento de Pessoal , Preparações Farmacêuticas , Processamento Eletrônico de Dados , Recursos Humanos
8.
Nat Commun ; 13(1): 5312, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085288

RESUMO

Response to immunotherapies can be variable and unpredictable. Pathology-based phenotyping of tumors into 'hot' and 'cold' is static, relying solely on T-cell infiltration in single-time single-site biopsies, resulting in suboptimal treatment response prediction. Dynamic vascular events (tumor angiogenesis, leukocyte trafficking) within tumor immune microenvironment (TiME) also influence anti-tumor immunity and treatment response. Here, we report dynamic cellular-level TiME phenotyping in vivo that combines inflammation profiles with vascular features through non-invasive reflectance confocal microscopic imaging. In skin cancer patients, we demonstrate three main TiME phenotypes that correlate with gene and protein expression, and response to toll-like receptor agonist immune-therapy. Notably, phenotypes with high inflammation associate with immunostimulatory signatures and those with high vasculature with angiogenic and endothelial anergy signatures. Moreover, phenotypes with high inflammation and low vasculature demonstrate the best treatment response. This non-invasive in vivo phenotyping approach integrating dynamic vasculature with inflammation serves as a reliable predictor of response to topical immune-therapy in patients.


Assuntos
Imunoterapia , Microambiente Tumoral , Humanos , Fatores Imunológicos , Inflamação , Fenótipo
11.
Endocr Pract ; 28(9): 884-888, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35753675

RESUMO

OBJECTIVE: To identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events. METHODS: Electronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmol/L, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA. RESULTS: A total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients; 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively. CONCLUSION: Euglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped.


Assuntos
Diabetes Mellitus Tipo 2 , Cetoacidose Diabética , Inibidores do Transportador 2 de Sódio-Glicose , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/epidemiologia , Cetoacidose Diabética/prevenção & controle , Glucose , Humanos , Incidência , Pacientes Internados , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
12.
Int J Ophthalmol ; 15(5): 820-827, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35601175

RESUMO

The presence of inflammation in dry eye disease (DED) results in increased patient symptomatology, ocular surface damage and worsening tear dysfunction. It also affects the health of meibomian glands and their secretions which further aggravates ocular surface disease. This article reviews current knowledge regarding ocular surface inflammation in DED and explores the relationships between the vicious cycles of DED, inflammation and meibomian gland dysfunction (MGD). The clinical evaluation of eyes with such changes, markers that identify the presence of inflammation on the ocular surface and current treatment options are discussed.

15.
J Immunother Cancer ; 9(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34635495

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are approved to treat multiple cancers. Retrospective analyses demonstrate acceptable safety of ICIs in most patients with autoimmune disease, although disease exacerbation may occur. Psoriasis vulgaris is a common, immune-mediated disease, and outcomes of ICI treatment in patients with psoriasis are not well described. Thus we sought to define the safety profile and effectiveness of ICIs in patients with pre-existing psoriasis. METHODS: In this retrospective cohort study, patients from eight academic centers with pre-existing psoriasis who received ICI treatment for cancer were evaluated. Main safety outcomes were psoriasis exacerbation and immune-related adverse events (irAEs). We also assessed progression-free survival (PFS) and overall survival. RESULTS: Of 76 patients studied (50 (66%) male; median age 67 years; 62 (82%) with melanoma, 5 (7%) with lung cancer, 2 (3%) with head and neck cancer, and 7 (9%) with other cancers; median follow-up 25.1 months (range=0.2-99 months)), 51 (67%) received anti-PD-1 antibodies, 8 (11%) anti-CTLA-4, and 17 (22%) combination of anti-PD-1/CTLA-4. All patients had pre-existing psoriasis, most frequently plaque psoriasis (46 patients (61%)) and 15 (20%) with psoriatic arthritis. Forty-one patients (54%) had received any prior therapy for psoriasis although only two (3%) were on systemic immunosuppression at ICI initiation. With ICI treatment, 43 patients (57%) experienced a psoriasis flare of cutaneous and/or extracutaneous disease after a median of 44 days of receiving ICI. Of those who experienced a flare, 23 patients (53%) were managed with topical therapy only; 16 (21%) needed systemic therapy. Only five patients (7%) required immunotherapy discontinuation for psoriasis flare. Forty-five patients (59%) experienced other irAEs, 17 (22%) of which were grade 3/4. PFS with landmark analysis was significantly longer in patients with a psoriasis flare versus those without (39 vs 8.7 months, p=0.049). CONCLUSIONS: In this multicenter study, ICI therapy was associated with frequent psoriasis exacerbation, although flares were manageable with standard psoriasis treatments and few required ICI discontinuation. Patients who experienced disease exacerbation performed at least as well as those who did not. Thus, pre-existing psoriasis should not prevent patients from receiving ICIs for treatment of malignancy.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Psoríase/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
Int J Obes (Lond) ; 45(11): 2347-2357, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34267326

RESUMO

BACKGROUND: A detailed characterization of patients with COVID-19 living with obesity has not yet been undertaken. We aimed to describe and compare the demographics, medical conditions, and outcomes of COVID-19 patients living with obesity (PLWO) to those of patients living without obesity. METHODS: We conducted a cohort study based on outpatient/inpatient care and claims data from January to June 2020 from Spain, the UK, and the US. We used six databases standardized to the OMOP common data model. We defined two non-mutually exclusive cohorts of patients diagnosed and/or hospitalized with COVID-19; patients were followed from index date to 30 days or death. We report the frequency of demographics, prior medical conditions, and 30-days outcomes (hospitalization, events, and death) by obesity status. RESULTS: We included 627 044 (Spain: 122 058, UK: 2336, and US: 502 650) diagnosed and 160 013 (Spain: 18 197, US: 141 816) hospitalized patients with COVID-19. The prevalence of obesity was higher among patients hospitalized (39.9%, 95%CI: 39.8-40.0) than among those diagnosed with COVID-19 (33.1%; 95%CI: 33.0-33.2). In both cohorts, PLWO were more often female. Hospitalized PLWO were younger than patients without obesity. Overall, COVID-19 PLWO were more likely to have prior medical conditions, present with cardiovascular and respiratory events during hospitalization, or require intensive services compared to COVID-19 patients without obesity. CONCLUSION: We show that PLWO differ from patients without obesity in a wide range of medical conditions and present with more severe forms of COVID-19, with higher hospitalization rates and intensive services requirements. These findings can help guiding preventive strategies of COVID-19 infection and complications and generating hypotheses for causal inference studies.


Assuntos
COVID-19/epidemiologia , Obesidade/epidemiologia , Adolescente , Adulto , Idoso , COVID-19/mortalidade , Estudos de Coortes , Comorbidade , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Espanha/epidemiologia , Reino Unido/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
17.
Artigo em Inglês | MEDLINE | ID: mdl-34059527

RESUMO

INTRODUCTION: To evaluate whether outpatient insulin treatment, hemoglobin A1c (HbA1c), glucose on admission, or glycemic control during hospitalization is associated with SARS-CoV-2 (COVID-19) illness severity or mortality in hospitalized patients with diabetes mellitus (DM) in a geographical region with low COVID-19 prevalence. RESEARCH DESIGN AND METHODS: A single-center retrospective study of patients hospitalized with COVID-19 from January 1 through August 31, 2020 to evaluate whether outpatient insulin use, HbA1c, glucose on admission, or average glucose during admission was associated with intensive care unit (ICU) admission, mechanical ventilation (ventilator) requirement, or mortality. RESULTS: Among 111 patients with DM, 48 (43.2%) were on outpatient insulin and the average HbA1c was 8.1% (65 mmol/mol). The average glucose on admission was 187.0±102.94 mg/dL and the average glucose during hospitalization was 173.4±39.8 mg/dL. Use of outpatient insulin, level of HbA1c, glucose on admission, or average glucose during hospitalization was not associated with ICU admission, ventilator requirement, or mortality among patients with COVID-19 and DM. CONCLUSIONS: Our findings in a region with relatively low COVID-19 prevalence suggest that neither outpatient glycemic control, glucose on admission, or inpatient glycemic control is predictive of illness severity or mortality in patients with DM hospitalized with COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus , Glicemia , Diabetes Mellitus/tratamento farmacológico , Controle Glicêmico , Humanos , Pacientes Internados , Pacientes Ambulatoriais , Estudos Retrospectivos , SARS-CoV-2
18.
J Contemp Brachytherapy ; 13(3): 280-285, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34122567

RESUMO

PURPOSE: The use of vaginal immobilization balloons placed into the vagina for immobilization of tandem and ovoid (T+O) applicator during high-dose-rate (HDR) brachytherapy delivery has been used at our institution, and seems to have improved our patient comfort, decreased procedure time, and minimized applicator misplacement. We aimed to show that these balloons, while originally marketed for single-day use, are safe and maintain applicator positioning/dosimetry when left in situ overnight for treatment delivery on sequential days. MATERIAL AND METHODS: Forty-two paired computed tomography (CT) scans from thirteen patients who underwent T+O HDR treatments on sequential days with vaginal immobilization balloons in situ overnight were retrospectively compared to calculate mean change of balloon volumes and balloon/T+O distance to bony landmarks. Dosimetric planning was retroactively performed on day 2 using CT scan of each pair, and the change in estimated radiation delivery to the bladder and rectum was compared. RESULTS: No statistically significant overnight changes were found in balloon volumes or anterior balloon positioning. The posterior balloon shifted -0.29 ±0.46 cm (p = 0.03) to the anterior public symphysis and 0.32 ±0.50 cm (p = 0.01) to the right femoral head. The tandem shifted 0.37 ±0.39 cm (p = 0.002) to the pubic symphysis. There was no significant difference found in radiation delivered to the bladder or rectum between the paired scans. CONCLUSIONS: This study showed minimal change in balloon volumes, balloons/T+O positioning, or in radiation dose to bladder and rectum when the applicator remained overnight. These findings support that inflatable vaginal immobilization balloons remaining in situ overnight for additional HDR T+O treatments on sequential days, is safe and provides stable dosimetry.

19.
BMJ ; 373: n1038, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33975825

RESUMO

OBJECTIVE: To investigate the use of repurposed and adjuvant drugs in patients admitted to hospital with covid-19 across three continents. DESIGN: Multinational network cohort study. SETTING: Hospital electronic health records from the United States, Spain, and China, and nationwide claims data from South Korea. PARTICIPANTS: 303 264 patients admitted to hospital with covid-19 from January 2020 to December 2020. MAIN OUTCOME MEASURES: Prescriptions or dispensations of any drug on or 30 days after the date of hospital admission for covid-19. RESULTS: Of the 303 264 patients included, 290 131 were from the US, 7599 from South Korea, 5230 from Spain, and 304 from China. 3455 drugs were identified. Common repurposed drugs were hydroxychloroquine (used in from <5 (<2%) patients in China to 2165 (85.1%) in Spain), azithromycin (from 15 (4.9%) in China to 1473 (57.9%) in Spain), combined lopinavir and ritonavir (from 156 (<2%) in the VA-OMOP US to 2,652 (34.9%) in South Korea and 1285 (50.5%) in Spain), and umifenovir (0% in the US, South Korea, and Spain and 238 (78.3%) in China). Use of adjunctive drugs varied greatly, with the five most used treatments being enoxaparin, fluoroquinolones, ceftriaxone, vitamin D, and corticosteroids. Hydroxychloroquine use increased rapidly from March to April 2020 but declined steeply in May to June and remained low for the rest of the year. The use of dexamethasone and corticosteroids increased steadily during 2020. CONCLUSIONS: Multiple drugs were used in the first few months of the covid-19 pandemic, with substantial geographical and temporal variation. Hydroxychloroquine, azithromycin, lopinavir-ritonavir, and umifenovir (in China only) were the most prescribed repurposed drugs. Antithrombotics, antibiotics, H2 receptor antagonists, and corticosteroids were often used as adjunctive treatments. Research is needed on the comparative risk and benefit of these treatments in the management of covid-19.


Assuntos
Tratamento Farmacológico da COVID-19 , Quimioterapia Adjuvante/métodos , Reposicionamento de Medicamentos/métodos , Demandas Administrativas em Assistência à Saúde/estatística & dados numéricos , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Azitromicina/uso terapêutico , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Ceftriaxona/uso terapêutico , Criança , Pré-Escolar , China/epidemiologia , Estudos de Coortes , Combinação de Medicamentos , Registros Eletrônicos de Saúde/estatística & dados numéricos , Enoxaparina/uso terapêutico , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Hidroxicloroquina/uso terapêutico , Lactente , Recém-Nascido , Pacientes Internados , Lopinavir/uso terapêutico , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Ritonavir/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , Segurança , Espanha/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Vitamina D/uso terapêutico , Adulto Jovem
20.
Diabetes ; 70(8): 1898-1909, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34021044

RESUMO

When stable and near-normoglycemic, patients with "A-ß+" ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A-ß+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without (n = 21) or with (n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and ß-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones-a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A-ß+ KPD is marked by chronic but varying dysregulation of BCAA metabolism.


Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Carnitina/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Cetoacidose Diabética/sangue , Adulto , Autoanticorpos , Carnitina/análogos & derivados , Feminino , Humanos , Masculino , Metaboloma , Metabolômica , Pessoa de Meia-Idade
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