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1.
JAMA Dermatol ; 160(1): 54-62, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38019562

RESUMO

Importance: Isotretinoin is hypothesized to contribute to the development of psychiatric disorders, but the epidemiological association and risk factors associated with psychiatric disorders among isotretinoin users remain unclear. Objective: To clarify the absolute and relative risk and risk factors associated with suicide and psychiatric disorders among isotretinoin users. Data Sources: PubMed, Embase, Web of Science, and Scopus were searched from inception until January 24, 2023. Study Selection: Randomized trials and observational studies were selected if they reported the absolute risk, relative risk, and risk factors for suicide and psychiatric disorders among isotretinoin users. Data Extraction and Synthesis: Relevant data were extracted and risk of bias was evaluated at the study level using the Newcastle-Ottawa Scale. Data were pooled using inverse variance-weighted meta-analyses. Heterogeneity was measured using the I2 statistic, and meta-regression analyses were performed. Main Outcomes and Measures: Absolute risk (percentage), relative risks (risk ratios [RR]), and risk factors (RR) of suicide and psychiatric disorders among isotretinoin users. Results: A total of 25 studies including 1 625 891 participants were included in the review and 24 in the meta-analysis. Among the included studies, participants' average age ranged from 16 to 38 years, and distribution by sex ranged from 0% to 100% male. The 1-year pooled absolute risk from between 2 and 8 studies of completed suicide, suicide attempt, suicide ideation, and self-harm were each less than 0.5%, while that of depression was 3.83% (95% CI, 2.45-5.93; I2 = 77%) in 11 studies. Isotretinoin users were less likely than nonusers to attempt suicide at 2 years (RR, 0.92; 95% CI, 0.84-1.00; I2 = 0%), 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%), and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment. Isotretinoin was not associated with the risk of all psychiatric disorders (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%). Study-level meta-regression found that studies with participants of older age reported lower 1-year absolute risk of depression, while those with a higher percentage of male participants reported a higher 1-year absolute risk of completed suicide. Conclusions and Relevance: The findings suggest that at a population level, isotretinoin users do not have increased risk of suicide or psychiatric conditions but may instead have a lower risk of suicide attempts at 2 to 4 years following treatment. While these findings are reassuring, clinicians should continue to practice holistic psychodermatologic care and monitor patients for signs of mental distress during isotretinoin treatment.


Assuntos
Isotretinoína , Transtornos Mentais , Humanos , Masculino , Adolescente , Adulto Jovem , Adulto , Feminino , Isotretinoína/efeitos adversos , Transtornos Mentais/epidemiologia , Tentativa de Suicídio/psicologia , Ideação Suicida , Fatores de Risco
2.
Heart Lung Circ ; 32(10): 1230-1239, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37743221

RESUMO

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.


Assuntos
Doenças Cardiovasculares , Insuficiência Cardíaca , Infarto do Miocárdio , Acidente Vascular Cerebral , Feminino , Humanos , Doenças Cardiovasculares/epidemiologia , Cálcio , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/prevenção & controle , Suplementos Nutricionais
3.
PLoS One ; 18(9): e0291036, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37703258

RESUMO

INTRODUCTION: In low-resource settings, midwives are the first contact for women with preeclampsia and lead the coordination of care. Unfavourable preeclampsia outcomes create a burden for women, families, and the health system. It is therefore important to understand the unique context of midwives' practice and the complex factors that influence the delivery of maternal healthcare. AIM: This qualitative study explored the perspectives of key stakeholders in a tertiary hospital in Ghana regarding the facilitators and barriers influencing midwives' provision of preeclampsia care using a socioecological model. METHODS: Semi-structured interviews were conducted with 42 participants comprising senior managers (n = 7) and hospital midwives (n = 35) in 2021. Thematic analysis used Braun and Clarke's six-step method, and the findings were organised within four levels of the socioecological model: individual, interpersonal, organisational, and public policy. RESULTS: Two main themes were identified: 1) Facilitators of preeclampsia management, and 2) Barriers to preeclampsia management. Facilitators were identified at three levels (individual, interpersonal, and organisational) and included midwives' knowledge of preeclampsia; midwives' self-efficacy; midwives' skillset to enhance preeclampsia care; collaborative practice; and strategies for preeclampsia care quality improvement. At the individual level, the barriers were inadequate pre-service preparation, lack of evidence-based midwifery care, and colleagues' work attitudes. Hierarchical decision-making and staff views of women's risk perceptions were identified as barriers at the interpersonal level. At the organisational level, the barriers were: scarce resources and staff shortages, and a lack of midwifery-specific guidelines. Two barriers were identified within the public policy level: the high cost of preeclampsia care and issues with the referral system. CONCLUSION: Multi-faceted factors play a significant role in midwives' management of preeclampsia. Hence context-specific multi-level interventions have the potential to improve the quality-of-care women in Ghana receive.


Assuntos
Tocologia , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Masculino , Centros de Atenção Terciária , Gana , Pré-Eclâmpsia/terapia , Encaminhamento e Consulta
4.
Clin Cancer Res ; 29(14): 2621-2630, 2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37289007

RESUMO

PURPOSE: To assess whether higher plasma 25-hydroxyvitamin D [25(OH)D] is associated with improved outcomes in colon cancer and whether circulating inflammatory cytokines mediate such association. EXPERIMENTAL DESIGN: Plasma samples were collected from 1,437 patients with stage III colon cancer enrolled in a phase III randomized clinical trial (CALGB/SWOG 80702) from 2010 to 2015, who were followed until 2020. Cox regressions were used to examine associations between plasma 25(OH)D and disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR). Mediation analysis was performed for circulating inflammatory biomarkers of C-reactive protein (CRP), IL6, and soluble TNF receptor 2 (sTNF-R2). RESULTS: Vitamin D deficiency [25(OH)D <12 ng/mL] was present in 13% of total patients at baseline and in 32% of Black patients. Compared with deficiency, nondeficient vitamin D status (≥12 ng/mL) was significantly associated with improved DFS, OS, and TTR (all Plog-rank<0.05), with multivariable-adjusted HRs of 0.68 (95% confidence interval, 0.51-0.92) for DFS, 0.57 (0.40-0.80) for OS, and 0.71 (0.52-0.98) for TTR. A U-shaped dose-response pattern was observed for DFS and OS (both Pnonlinearity<0.05). The proportion of the association with survival that was mediated by sTNF-R2 was 10.6% (Pmediation = 0.04) for DFS and 11.8% (Pmediation = 0.05) for OS, whereas CRP and IL6 were not shown to be mediators. Plasma 25(OH)D was not associated with the occurrence of ≥ grade 2 adverse events. CONCLUSIONS: Nondeficient vitamin D is associated with improved outcomes in patients with stage III colon cancer, largely independent of circulation inflammations. A randomized trial is warranted to elucidate whether adjuvant vitamin D supplementation improves patient outcomes.


Assuntos
Neoplasias do Colo , Interleucina-6 , Humanos , Vitamina D , Vitaminas , Intervalo Livre de Doença , Proteína C-Reativa
5.
Br J Cancer ; 129(2): 283-290, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37179438

RESUMO

BACKGROUND: We sought to assess the influences of sleep duration, sleep adequacy, and daytime sleepiness on survival outcomes among Stage III colon cancer patients. METHODS: We conducted a prospective observational study of 1175 Stage III colon cancer patients enrolled in the CALGB/SWOG 80702 randomised adjuvant chemotherapy trial who completed a self-reported questionnaire on dietary and lifestyle habits 14-16 months post-randomisation. The primary endpoint was disease-free survival (DFS), and secondary was overall survival (OS). Multivariate analyses were adjusted for baseline sociodemographic, clinical, dietary and lifestyle factors. RESULTS: Patients sleeping ≥9 h-relative to 7 h-experienced a worse hazard ratio (HR) of 1.62 (95% confidence interval (CI), 1.01-2.58) for DFS. In addition, those sleeping the least (≤5 h) or the most (≥ 9 h) experienced worse HRs for OS of 2.14 (95% CI, 1.14-4.03) and 2.34 (95% CI, 1.26-4.33), respectively. Self-reported sleep adequacy and daytime sleepiness showed no significant correlations with outcomes. CONCLUSIONS: Among resected Stage III colon cancer patients who received uniform treatment and follow-up within a nationwide randomised clinical trial, very long and very short sleep durations were significantly associated with increased mortality. Interventions targeting optimising sleep health among indicated colon cancer patients may be an important method by which more comprehensive care can be delivered. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01150045.


Assuntos
Neoplasias do Colo , Distúrbios do Sono por Sonolência Excessiva , Qualidade do Sono , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Intervalo Livre de Doença , Humanos , Estudos Prospectivos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso
6.
Langenbecks Arch Surg ; 408(1): 21, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36635455

RESUMO

OBJECTIVE: The effectiveness of adjuvant radioiodine (RAI) after reoperation in patients with persistent or recurrent differentiated thyroid cancer (DTC) is controversial. Although various organizations recognize that strong evidence for the use of RAI is lacking, they continue to recommend the use of adjuvant RAI therapy for select groups of patients. This is concerning as RAI therapy has potential side effects such as gastrointestinal symptoms, bone marrow suppression, and gonadal damage. METHODS: Four electronic databases were systematically searched for randomized trials or observational studies that examined the outcomes of adjuvant RAI after reoperation for recurrent DTC, among patients of any age. The baseline characteristics, treatment response, disease progression, and overall survival of these studies were synthesized and reported. A meta-analysis of the use of RAI on progression-free survival was also performed. RESULTS: Six observational studies, comprising a combined cohort of 437 patients who underwent reoperation, were included from 1212 records. Adjuvant RAI after reoperation in recurrent DTC was not associated with longer progression-free or overall survival. There was also no association of RAI with excellent structural or biochemical treatment response, lower thyroglobulin levels, nor a lower rate of second recurrence or distant metastases. CONCLUSIONS: Adjuvant RAI after reoperation in recurrent DTC was not associated with improved cancer or treatment-related outcomes. However, as the included studies were of inadequate quality, there is an urgent need for randomized trials and well-analyzed cohort studies. Physicians should exercise clinical judgment to prescribe adjuvant RAI for only selected, high-risk patients.


Assuntos
Adenocarcinoma , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/diagnóstico , Radioisótopos do Iodo/uso terapêutico , Reoperação , Recidiva Local de Neoplasia/radioterapia , Recidiva Local de Neoplasia/cirurgia , Adenocarcinoma/cirurgia , Estudos Retrospectivos , Tireoidectomia
7.
J Clin Oncol ; 41(5): 1079-1091, 2023 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-36367997

RESUMO

PURPOSE: We sought to evaluate the independent and interactive associations of planned treatment duration, celecoxib use, physical activity, body mass index (BMI), diabetes mellitus, and vitamin B6 with oxaliplatin-induced peripheral neuropathy (OIPN) among patients with stage III colon cancer enrolled in a clinical trial. METHODS: We conducted a prospective, observational study of 2,450 patients with stage III colon cancer enrolled in the CALGB/SWOG 80702 trial, randomly assigned to 6 versus 12 cycles of adjuvant fluorouracil, leucovorin, and oxaliplatin chemotherapy with or without 3 years of celecoxib. OIPN was reported using the Common Terminology Criteria for Adverse Events (CTCAE) during and following completion of chemotherapy and the FACT/GOG-NTX-13 15-17 months after random assignment. Multivariate analyses were adjusted for baseline sociodemographic and clinical factors. RESULTS: Patients assigned to 12 treatment cycles, relative to 6, were significantly more likely to experience higher-grade CTCAE- and FACT/GOG-NTX-13-reported neuropathy and longer times to resolution, while neither celecoxib nor vitamin B6 intake attenuated OIPN. Exercising ≥ 9 MET-hours per week after treatment relative to < 9 was associated with improvements in FACT/GOG-NTX-13-reported OIPN (adjusted difference in means, 1.47; 95% CI, 0.49 to 2.45; P = .003). Compared with patients with baseline BMIs < 25, those with BMIs ≥ 25 were at significantly greater risk of developing higher-grade CTCAE-reported OIPN during (adjusted odds ratio, 1.18; 95% CI, 1.00 to 1.40; P = .05) and following completion (adjusted odds ratio, 1.23; 95% CI, 1.01 to 1.50; P = .04) of oxaliplatin treatment. Patients with diabetes were significantly more likely to experience worse FACT/GOG-NTX-13-reported neuropathy relative to those without (adjusted difference in means, -2.0; 95% CI, -3.3 to -0.73; P = .002). There were no significant interactions between oxaliplatin treatment duration and any of these potentially modifiable exposures. CONCLUSION: Lower physical activity, higher BMI, diabetes, and longer planned treatment duration, but not celecoxib use or vitamin B6 intake, may be associated with significantly increased OIPN severity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Colo , Oxaliplatina , Doenças do Sistema Nervoso Periférico , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Estudos Prospectivos
8.
J Clin Oncol ; 41(2): 243-254, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35944235

RESUMO

PURPOSE: To determine the specific types, durations, and intensities of recreational physical activity associated with the greatest improvements in disease-free survival (DFS) of patients with colon cancer. METHODS: We conducted a prospective cohort study nested within a randomized multicenter trial of stage III colon cancer that compared 3 versus 6 months of fluorouracil, leucovorin, and oxaliplatin with or without celecoxib. We measured recreational physical activity in the first 3 months of chemotherapy and again 6 months after completion of chemotherapy. The primary end point was DFS. RESULTS: During a median follow-up of 5.9 years, 457 of 1,696 patients experienced disease recurrence or death. For total recreational physical activity volume, the 3-year DFS was 76.5% with < 3.0 metabolic equivalent task hours per week (MET-h/wk) and 87.1% with ≥ 18.0 MET-h/wk (risk difference [RD], 10.6%; 95% CI, 4.7 to 19.4; P < .001). For light-intensity to moderate-intensity activities, the 3-year DFS was 65.7% with 0.0 h/wk and 87.1% with ≥ 1.5 h/wk (RD, 21.4%; 95% CI, 9.2 to 37.1; P < .001). For vigorous-intensity activity, the 3-year DFS was 76.0% with 0.0 h/wk and 86.0% with ≥ 1.0 h/wk (RD, 10.0%; 95% CI, 4.5 to 18.9; P < .001). For brisk walking, the 3-year DFS was 81.7% with < 1.0 h/wk and 88.4% with ≥ 3.0 h/wk (RD, 6.7%; 95% CI, 3.0 to 13.8; P < .001). For muscle strengthening activity, the 3-year DFS was 81.8% with 0.0 h/wk and 88.8% for ≥ 0.5 h/wk (RD, 7.0%; 95% CI, 3.1 to 14.2; P = .003). CONCLUSION: Among patients with stage III colon cancer enrolled in a trial of postoperative treatment, larger volumes of recreational physical activity, longer durations of light- to moderate-intensity aerobic physical activity, or any vigorous-intensity aerobic physical activity were associated with the greatest improvements in DFS.


Assuntos
Neoplasias do Colo , Recidiva Local de Neoplasia , Humanos , Estudos Prospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Exercício Físico , Fluoruracila/uso terapêutico , Intervalo Livre de Doença , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucovorina/uso terapêutico , Estadiamento de Neoplasias
9.
Clin Infect Dis ; 74(5): 905-908, 2022 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-34079986

RESUMO

We report a case of resistance development toward cefiderocol in a patient with intra-abdominal and bloodstream infections caused by carbapenemase-producing Enterobacter cloacae within 21 days of cefiderocol therapy. Whole genome sequencing revealed heterogeneous mutations in the cirA gene, encoding a catecholate siderophore receptor, conferring phenotypic resistance to cefiderocol.


Assuntos
Enterobacter cloacae , Sideróforos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Carbapenêmicos/uso terapêutico , Cefalosporinas , Enterobacter cloacae/genética , Humanos , Testes de Sensibilidade Microbiana , Mutação , Sideróforos/uso terapêutico , beta-Lactamases/genética , Cefiderocol
10.
J Thromb Thrombolysis ; 50(3): 596-603, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32661758

RESUMO

The Coronavirus disease 2019 (COVID-19) pandemic is rapidly evolving and affecting healthcare systems across the world. Singapore has escalated its alert level to Disease Outbreak Response System Condition (DORSCON) Orange, signifying severe disease with community spread. We aimed to study the overall volume of AIS cases and the delivery of hyperacute stroke services during DORSCON Orange. This was a single-centre, observational cohort study performed at a comprehensive stroke centre responsible for AIS cases in the western region of Singapore, as well as providing care for COVID-19 patients. All AIS patients reviewed as an acute stroke activation in the Emergency Department (ED) from November 2019 to April 2020 were included. System processes timings, treatment and clinical outcome variables were collected. We studied 350 AIS activation patients admitted through the ED, 206 (58.9%) pre- and 144 during DORSCON Orange. Across the study period, number of stroke activations showed significant decline (p = 0.004, 95% CI 6.513 to - 2.287), as the number of COVID-19 cases increased exponentially, whilst proportion of activations receiving acute recanalization therapy remained stable (p = 0.519, 95% CI - 1.605 to 2.702). Amongst AIS patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h (-4 versus -4, p = 0.685) were largely similar between the pre- and during DORSCON orange periods. The number of stroke activations decreased while the proportion receiving acute recanalization therapy remained stable in the current COVID-19 pandemic in Singapore.


Assuntos
Assistência Integral à Saúde/organização & administração , Infecções por Coronavirus/terapia , Prestação Integrada de Cuidados de Saúde/organização & administração , Necessidades e Demandas de Serviços de Saúde/organização & administração , Pneumonia Viral/terapia , Acidente Vascular Cerebral/terapia , Idoso , COVID-19 , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Equipe de Assistência ao Paciente/organização & administração , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Recuperação de Função Fisiológica , Encaminhamento e Consulta/organização & administração , Singapura/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Tempo para o Tratamento/organização & administração , Resultado do Tratamento , Fluxo de Trabalho
11.
J Thromb Thrombolysis ; 46(1): 68-73, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29616407

RESUMO

Left ventricular (LV) thrombus is commonly seen in patients with extensive anterior ST-elevation myocardial infarction. The standard of care for LV thrombus is anticoagulation with warfarin. However, there has been an increasing trend of case reports using non-vitamin K antagonist oral anticoagulants (NOAC) for the treatment of LV thrombus. This study aimed to perform a meta-summary of the literature to characterise and evaluate the safety and feasibility of using NOAC in patients with LV thrombus. We searched for articles published in four electronic databases: PubMed, EMBASE, Scopus and Google Scholar using an appropriate keyword/MeSH term search strategy. Twenty-four studies comprising 36 patients were included in the analysis. Rivaroxaban was used in majority of patients (47.2%), whilst Apixaban and Dabigatran were prescribed in 25.0% and 27.8% of patients respectively. The most commonly associated risk factor found was post-acute myocardial infarction in 15 patients (41.7%). LV thrombus resolution was met by most patients (87.9%), and the median duration of treatment to resolution was 30.0 days (IQR = 22.5-47.0). One non-fatal bleeding event (3.0%) and no embolic events were reported. The use of NOAC may have a role in the treatment of LV thrombus in selected patients. Further randomized controlled trials are needed to evaluate this treatment strategy.


Assuntos
Anticoagulantes/uso terapêutico , Trombose/tratamento farmacológico , Disfunção Ventricular Esquerda/dietoterapia , Administração Oral , Anticoagulantes/efeitos adversos , Dabigatrana/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/etiologia , Pirazóis/uso terapêutico , Piridonas/uso terapêutico , Rivaroxabana/uso terapêutico , Trombose/complicações
12.
J Stroke Cerebrovasc Dis ; 27(6): 1539-1545, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29422380

RESUMO

BACKGROUND: In acute ischemic stroke (AIS), treatment with intravenous tissue-type plasminogen activator (IV-tPA) is time-sensitive. All stroke centers make continual efforts to reduce door-to-needle time (DNT) with varying success. We present the impact of modifications to our stroke activation protocol on DNT. METHODS: We included 404 consecutive patients with AIS receiving IV-tPA between January 2014 and December 2016. First changes in stroke activation protocol were made in March 2015 in the form of prenotification by paramedics, direct transfer from ambulance to computed tomography (CT) scanner, and rapid en route neurological assessment by an emergency physician and neurologist. In March 2016, a second amendment was made where a stroke nurse accompanied the patient to expedite various steps in the treatment pathway, including endovascular treatment in eligible cases. RESULTS: Both protocol amendments resulted in improvement in DNT and door-to-CT time from 84 ± 47 minutes before intervention to 69 ± 33 minutes after protocol amendment 1 to 59 ± 37 minutes after protocol amendment 2. In particular, the second amendment (144 patients) showed significant shortening of DNT compared with the 137 patients before (59 ± 37 minutes versus 69 ± 33 minutes, P = .020), with a higher percentage achieving the target of 60 minutes (68.1% versus 48.2%, P < .001). This finding was attributed to a reduction in both door-to-CT time and CT-to-needle time. This improvement remained consistent over subsequent months. CONCLUSIONS: The application of a simple systems-based, multidisciplinary stroke activation protocol may help in significant reduction in DNT. Encouraging increased patient ownership by stroke nurses appeared to be a promising approach for timely administration of definitive acute therapies.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Prestação Integrada de Cuidados de Saúde/organização & administração , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Tempo para o Tratamento/organização & administração , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Pessoal Técnico de Saúde/organização & administração , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Protocolos Clínicos , Serviço Hospitalar de Emergência/organização & administração , Fibrinolíticos/efeitos adversos , Humanos , Exame Neurológico , Neurologistas/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Centros de Atenção Terciária , Terapia Trombolítica/efeitos adversos , Fatores de Tempo , Ativador de Plasminogênio Tecidual/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Int J Radiat Oncol Biol Phys ; 99(2): 417-426, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28871992

RESUMO

PURPOSE: To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. METHODS AND MATERIALS: Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. RESULTS: Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). CONCLUSIONS: Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution.


Assuntos
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia/métodos , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/mortalidade , Neoplasias Retais/terapia , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Cuidados Pré-Operatórios , Radioterapia/métodos , Neoplasias Retais/mortalidade , Neoplasias Retais/patologia
14.
HPB (Oxford) ; 19(5): 449-457, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28162923

RESUMO

To report long-term follow up of a phase II, single-arm trial of resectable pancreatic ductal adenocarcinoma (PDAC) treated with adjuvant interferon-based chemoradiation followed by gemcitabine to determine survival, recurrence, and complications. METHODS: From 2002 to 2005, 53 patients with PDAC underwent pancreaticoduodenectomy and received adjuvant interferon-based chemoradiation consisting of external-beam irradiation and simultaneous 3-drug chemotherapy of continuous daily 5-fluorouracil infusion, weekly intravenous bolus cisplatin, and subcutaneous interferon-α, followed by two months of weekly intravenous gemcitabine. RESULTS: Actual overall survival for the 5- and 10-year periods were 26% and 10%, respectively, with a median overall survival of 25 months (95% CI: 16.4-38.5). Adverse prognostic factors on multivariate analysis were positive tumor margin (p < 0.035), lymphovascular invasion (p < 0.015), and perineural invasion (p < 0.026). Median time to recurrence was 11 months. Positive tumor margin was associated with lymph node involvement (p < 0.005), portal vein resection (p < 0.038), and metastases (p < 0.018). Late complications were frequent and predominated by gastrointestinal and infectious complications. CONCLUSIONS: Adjuvant interferon-based chemoradiation for PDAC improves long-term survival compared to standard therapy. However, recurrence rates and long-term complications remain high, thus further studies are indicated to assess patient characteristics that indicate a favorable treatment profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Ductal Pancreático/terapia , Desoxicitidina/análogos & derivados , Fracionamento da Dose de Radiação , Interferon-alfa/administração & dosagem , Neoplasias Pancreáticas/terapia , Pancreaticoduodenectomia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/secundário , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Distribuição de Qui-Quadrado , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Interferon-alfa/efeitos adversos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Missouri , Análise Multivariada , Recidiva Local de Neoplasia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Gencitabina
15.
HPB (Oxford) ; 19(2): 133-139, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27916436

RESUMO

BACKGROUND & OBJECTIVES: Multidisciplinary tumor boards (MDTBs) are frequently employed in cancer centers but their value has been debated. We reviewed the decision-making process and resource utilization of our MDTB to assess its utility in the management of pancreatic and upper gastrointestinal tract conditions. METHODS: A prospectively-collected database was reviewed over a 12-month period. The primary outcome was change in management plan as a result of case discussion. Secondary outcomes included resources required to hold MDTB, survival, and adherence to treatment guidelines. RESULTS: Four hundred seventy cases were reviewed. MDTB resulted in a change in the proposed plan of management in 101 of 402 evaluable cases (25.1%). New plans favored obtaining additional diagnostic workup. No recorded variables were associated with a change in plan. For newly-diagnosed cases of pancreatic ductal adenocarcinoma (n = 33), survival time was not impacted by MDTB (p = .154) and adherence to National Comprehensive Cancer Network guidelines was 100%. The estimated cost of physician time per case reviewed was $190. CONCLUSIONS: Our MDTB influences treatment decisions in a sizeable number of cases with excellent adherence to national guidelines. However, this requires significant time expenditure and may not impact outcomes. Regular assessments of the effectiveness of MDTBs should be undertaken.


Assuntos
Carcinoma Ductal Pancreático/terapia , Tomada de Decisão Clínica , Prestação Integrada de Cuidados de Saúde/estatística & dados numéricos , Neoplasias Gastrointestinais/terapia , Recursos em Saúde/estatística & dados numéricos , Comunicação Interdisciplinar , Neoplasias Pancreáticas/terapia , Equipe de Assistência ao Paciente/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal Pancreático/economia , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Bases de Dados Factuais , Prestação Integrada de Cuidados de Saúde/economia , Prestação Integrada de Cuidados de Saúde/normas , Feminino , Neoplasias Gastrointestinais/economia , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Fidelidade a Diretrizes , Custos de Cuidados de Saúde , Recursos em Saúde/economia , Recursos em Saúde/normas , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Equipe de Assistência ao Paciente/economia , Equipe de Assistência ao Paciente/normas , Guias de Prática Clínica como Assunto , Resultado do Tratamento , Adulto Jovem
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