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2.
J Clin Anesth ; 78: 110674, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35168136

RESUMO

STUDY OBJECTIVE: In the United States, alcohol use disorder adversely affects 5.6% of all adults. Excessive alcohol consumption adversely affects organ functions critical for adaptation to stress induced by surgery. Colorectal resection is one of the most common major surgeries in patients at risk for alcohol use disorder. The objective of this study was to assess the impact of alcohol use disorder on hospital outcomes after colectomy using a population-based discharge database. SETTING: Population-based discharge database. PATIENTS: The Premier Healthcare Database was queried for the 603,730 adult patients who underwent colectomy from 2016 to 2019. INTERVENTIONS: None. MEASUREMENTS: Multiple logistic regressions estimated the associations between in-hospital mortality, length of stay, and hospitalization cost with alcohol use disorder as the primary predictor, adjusting for other substance use disorders, psychotic disorders, depression, other Elixhauser comorbidities, age, payor, race, gender, non-elective surgery, and other unbalanced variables. MAIN RESULTS: A discharge code for alcohol use disorder was identified in 2.9% of colectomy patients and the overall in-hospital mortality rate in all sampled colectomy patients was 1.4%. Alcohol use disorder was associated with a significantly increased risk of in-hospital mortality after adjusting for other factors (AOR 1.36, 95% CI 1.24-1.48, p < 0.0001). Alcohol use disorder was also significantly associated with long length of stay (AOR 1.45, 95% CI 1.39-1.52, p < 0.0001) and high hospitalization costs (AOR 1.63, 95% CI 1.56-1.70, p < 0.0001). CONCLUSIONS: Alcohol use disorder is associated with an increased risk of in-hospital mortality in patients undergoing colectomy, one of the most common major surgeries. Future research should examine if enhanced efforts to identify patients with alcohol use disorder could enable anesthesiologists to provide worthwhile perioperative interventions for this high-risk population.


Assuntos
Alcoolismo , Adulto , Consumo de Bebidas Alcoólicas , Alcoolismo/complicações , Alcoolismo/epidemiologia , Colectomia/efeitos adversos , Mortalidade Hospitalar , Hospitais , Humanos , Tempo de Internação , Estudos Retrospectivos , Estados Unidos/epidemiologia
3.
Ann Fam Med ; 18(2): 118-126, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32152015

RESUMO

PURPOSE: Although cesarean delivery is the most common surgical procedure in the United States, postoperative opioid prescribing varies greatly. We hypothesized that patient characteristics, procedural characteristics, or both would be associated with high vs low opioid use after discharge. This information could help individualize prescriptions. METHODS: In this prospective cohort study, we quantified opioid use for 4 weeks following hospital discharge after cesarean delivery. Predischarge characteristics were obtained from health records, and patients self-reported total opioid use postdischarge on weekly questionnaires. Opioid use was quantified in milligram morphine equivalents (MMEs). Binomial and Poisson regression analyses were performed to assess predictors of opioid use after discharge. RESULTS: Of the 233 patients starting the study, 203 (87.1%) completed at least 1 questionnaire and were included in analyses (86.3% completed all 4 questionnaires). A total of 113 patients were high users (>75 MMEs) and 90 patients were low users (≤75 MMEs) of opioids postdischarge. The group reporting low opioid use received on average 44% fewer opioids in the 24 hours before discharge compared with the group reporting high opioid use (mean = 33.0 vs 59.3 MMEs, P <.001). Only a minority of patients (11.4% to 15.8%) stored leftover opioids in a locked location, and just 31 patients disposed of leftover opioids. CONCLUSIONS: Knowledge of predischarge opioid use can be useful as a tool to inform individualized opioid prescriptions, help optimize nonopioid analgesia, and reduce opioid use. Additional studies are needed to evaluate the impact of implementing such measures on prescribing practices, pain, and functional outcomes.


Assuntos
Analgésicos Opioides/uso terapêutico , Cesárea , Dor Pós-Operatória/tratamento farmacológico , Cuidado Pós-Natal/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Colorado , Feminino , Humanos , Medição da Dor , Alta do Paciente , Gravidez , Estudos Prospectivos , Análise de Regressão
4.
Mol Cancer Ther ; 18(2): 278-288, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30482852

RESUMO

Molecularly-targeted agents have improved outcomes for a subset of patients with BRAF-mutated melanoma, but treatment of resistant and BRAF wild-type tumors remains a challenge. The MERTK receptor tyrosine kinase is aberrantly expressed in melanoma and can contribute to oncogenic phenotypes. Here we report the effect of treatment with a MERTK-selective small molecule inhibitor, UNC2025, in preclinical models of melanoma. In melanoma cell lines, treatment with UNC2025 potently inhibited phosphorylation of MERTK and downstream signaling, induced cell death, and decreased colony formation. In patient-derived melanoma xenograft models, treatment with UNC2025 blocked or significantly reduced tumor growth. Importantly, UNC2025 had similar biochemical and functional effects in both BRAF-mutated and BRAF wild-type models and irrespective of NRAS mutational status, implicating MERTK inhibition as a potential therapeutic strategy in tumors that are not amenable to BRAF-targeting and for which there are limited treatment options. In BRAF-mutated cell lines, combined treatment with UNC2025 and the BRAF inhibitor vemurafenib provided effective inhibition of oncogenic signaling through ERK, AKT, and STAT6, increased induction of cell death, and decreased colony-forming potential. Similarly, in NRAS-mutated cell lines, addition of UNC2025 to cobimetinib therapy increased cell death and decreased colony-forming potential. In a BRAF-mutated patient-derived xenograft, treatment with combined UNC2025 and vemurafenib was well-tolerated and significantly decreased tumor growth compared with vemurafenib alone. These data support the use of UNC2025 for treatment of melanoma, irrespective of BRAF or NRAS mutational status, and suggest a role for MERTK and targeted combination therapy in BRAF and NRAS-mutated melanoma.


Assuntos
Adenina/análogos & derivados , Melanoma/tratamento farmacológico , Mutação , Piperazinas/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/genética , c-Mer Tirosina Quinase/metabolismo , Adenina/administração & dosagem , Adenina/farmacologia , Animais , Azetidinas/administração & dosagem , Azetidinas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , GTP Fosfo-Hidrolases/genética , Humanos , Melanoma/genética , Melanoma/metabolismo , Proteínas de Membrana/genética , Camundongos , Fosforilação/efeitos dos fármacos , Piperazinas/farmacologia , Piperidinas/administração & dosagem , Piperidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Vemurafenib/administração & dosagem , Vemurafenib/farmacologia
5.
J Am Board Fam Med ; 31(6): 941-943, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30413550

RESUMO

PURPOSE: The opioid epidemic in the United States is an ongoing public health concern. Health care institutions use standardized patient satisfaction surveys to assess the patient experience and some offer incentives to their providers based on the results. We hypothesized that providers who report being incentivized based on patient satisfaction surveys are more likely to report an impact of such surveys on their opioid prescribing practices. METHODS: We developed a 23-item survey instrument to assess the self-perceived impact of patient satisfaction surveys on opioid prescribing practices in primary care and the potential impact of institutional incentives. The survey was emailed to all 1404 members of the Colorado Academy of Family Physicians. RESULTS: The response rate to the online survey was 10.4% (n = 146). Clinical indications for which responders prescribe opioids included acute pain (93%), cancer pain (85%), and chronic nonmalignant pain (72%). Among physicians using patient satisfaction surveys, incentivized physicians reported at least a slight impact on opioid prescribing 3 times more often than physicians who were not incentivized (36% vs 12%, P = .004). CONCLUSIONS: Efforts to improve patient satisfaction may have potentially untoward effects on providers' opioid prescribing behaviors. Our results suggest a need to further study the impact of provider incentive plans that are based on patient satisfaction scores.


Assuntos
Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Satisfação do Paciente , Planos de Incentivos Médicos , Médicos de Família/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Atitude do Pessoal de Saúde , Colorado , Correio Eletrônico/estatística & dados numéricos , Epidemias/prevenção & controle , Humanos , Motivação , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Médicos de Família/psicologia , Padrões de Prática Médica/estatística & dados numéricos , Atenção Primária à Saúde/economia , Atenção Primária à Saúde/organização & administração , Inquéritos e Questionários/estatística & dados numéricos
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