RESUMO
BACKGROUND/OBJECTIVE: The potential correlation between herpes simplex virus (HSV) and human papillomavirus (HPV) infections and rheumatoid arthritis (RA) has not been definitively established. Further research is needed to determine the relationship between the development of RA and the presence of these viral infections. METHODS: A case-control study was conducted with data from the National Health and Nutrition Examination Survey between 2009 and 2014. Our analysis examined the association between HSV I, HSV II, HPV oral polymerase chain reaction (PCR), HPV vaginal PCR, and RA. We identified adults aged 20 to 49 years with a primary diagnosis of RA using the National Health and Nutrition Examination Survey database codes (MCQ191 = 1 [years 2009-2010]; MCQ195 = 2 [years 2011-2014]) and excluded patients with incomplete data on key variables and primary outcomes. RESULTS: The study included 8620 patients, with 150 patients diagnosed with RA and 1500 patients without RA. Patients with RA had a significantly higher prevalence of HSV II infection compared with those without RA (36.34% vs. 24.72%, p = 0.015) after propensity score matching. No significant differences were observed for HSV I, HPV oral PCR, and HPV vaginal PCR between the 2 groups. Patients with RA were older; were more likely to be female, obese, and non-Hispanic White; and had a higher prevalence of comorbidities than those without RA. CONCLUSIONS: This population-based propensity score-matching study provides evidence of an association between HSV II infection and RA in US adults. Further research is needed to fully elucidate the relationship between viral infections and RA, with the aim of developing effective risk reduction strategies and innovative treatments for RA.
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Artrite Reumatoide , Herpes Simples , Infecções por Papillomavirus , Adulto , Humanos , Feminino , Masculino , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/complicações , Estudos de Casos e Controles , Inquéritos Nutricionais , Pontuação de Propensão , Herpes Simples/diagnóstico , Herpes Simples/epidemiologia , Herpes Simples/complicações , Simplexvirus , Artrite Reumatoide/epidemiologia , Artrite Reumatoide/complicaçõesRESUMO
Ischemic preconditioning with non-lethal ischemia can be protective against lethal forebrain ischemia. We hypothesized that aging may aggravate ischemic susceptibility and reduce brain plasticity against preconditioning. Magnetic resonance diffusion tensor imaging (DTI) is a sensitive tool to detect brain integrity and white matter architecture. This study used DTI and histopathology to investigate the effect of aging on ischemic preconditioning. In this study, adult and middle-aged male Mongolian gerbils were subjected to non-lethal 5-min forebrain ischemia (ischemic preconditioning) or sham-operation, followed by 3 days of reperfusion, and then lethal 15-min forebrain ischemia. A 9.4-Tesla MR imaging system was used to study DTI indices, namely fractional anisotropy (FA), mean diffusivity (MD), and intervoxel coherence (IC) in the hippocampal CA1 and dentate gyrus (DG) areas. In situ expressions of microtubule-associated protein 2 (MAP2, dendritic marker protein) and apoptosis were also examined. The 5-min ischemia did not cause dendritic and neuronal injury and any significant change in DTI indices and MAP2 in adult and middle-aged gerbils. The 15-min ischemia-induced significant delayed neuronal apoptosis and early dendritic injury evidenced by DTI and MAP2 studies in both CA1 and DG areas with more severe injury in middle-aged gerbils than adult gerbils. Ischemic preconditioning could improve neuronal apoptosis in CA1 area and dendritic integrity in both CA1 and DG areas with better improvement in adult gerbils than middle-aged gerbils. This study thus suggests an age-dependent protective effect of ischemic preconditioning against both neuronal apoptosis and dendritic injury in hippocampus after forebrain ischemia.
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Envelhecimento/fisiologia , Apoptose/fisiologia , Dendritos/fisiologia , Hipocampo/fisiologia , Precondicionamento Isquêmico/métodos , Neurônios/fisiologia , Envelhecimento/patologia , Animais , Dendritos/patologia , Imagem de Tensor de Difusão/métodos , Gerbillinae , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Masculino , Neurônios/patologia , Prosencéfalo/diagnóstico por imagem , Prosencéfalo/patologia , Prosencéfalo/fisiologiaRESUMO
OBJECTIVE: Sexual dysfunction has been reported in women following treatment for gynecological cancer. However, the actual sexual activities adopted by these women are not well understood. The aims of this study were to (1) explore a relatively new concept, diversity of sexual activities (DSA), and (2) identify factors associated with DSA in women with gynecological cancer. METHODS: This cross-sectional study included 136 Taiwanese long-term partnered women with gynecologic cancer treated in a large medical center. DSA was measured with the Diversity of Sexual Activities Scale, which assesses the number of sexual activities adopted in the past 6 months. Covariates included sexual knowledge and sexual attitudes, perceived changes in relationships of intimacy since treatment, and demographic and clinical factors. RESULTS: The mean age of participants was 51.2 years (SD = 8.66); cancer diagnoses were cervical (50.7%), endometrial (31.6%), and ovarian (17.6%). The mean number of sexual activities was 2.88 (SD = 2.63); 29.4% of participants had no physical contact with their partners after treatment. The participants reported a significantly decreased overall satisfaction toward adopted sexual activities after cancer treatment. Lower DSA was associated with older age and receiving a combination of chemotherapy and radiotherapy. CONCLUSIONS: Cancer treatment has a significant impact on sexual activity in women with gynecological cancer. Around 30% of participants reported not having any physical contact with their partners since receiving cancer treatment. Sexual rehabilitation counseling that emphasizes alternative forms of sexual expression is suggested.
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Neoplasias dos Genitais Femininos/complicações , Comportamento Sexual , Disfunções Sexuais Fisiológicas/psicologia , Adulto , Estudos Transversais , Feminino , Neoplasias dos Genitais Femininos/psicologia , Neoplasias dos Genitais Femininos/terapia , Humanos , Pessoa de Meia-Idade , Parceiros Sexuais/psicologia , Inquéritos e Questionários , TaiwanRESUMO
BACKGROUND: Nasogastric intubation (NGI) is usually challenging in patients under general anesthesia, with reported success rate at the first attempt to be less than 50%. The aim of this study was to investigate whether a preinstalled nasopharyngeal airway (NPA) in the right nasal passageway can facilitate NGI in anesthetized and intubated patients. METHODS: A prospective randomized controlled trial including 108 patients scheduled for elective intra-abdominal surgeries requiring a nasogastric tube (NGT) was conducted. Fifty-three patients were randomized to receive NGI through a preinstalled NPA in the right nasal passageway (Group NPA) and 55 patients to receive NGI via the right nostril (Group O). The primary outcomes were success rates of NGI at first attempt, success rates of NGI in accumulative attempts, durations of successful NGI at the first attempt and success rates of NGI for the rescuing methods. The secondary outcomes were bleeding incidence and hemodynamic changes induced by NGI. RESULTS: Success rate of NGI at the first attempt was 83.0% in Group NPA compared with 47.3% in Group O [P < 0.001; absolute risk reduction (ARR) = 35.7%, 95% confidence interval (CI) = 19.1-52.4%; relative risk reduction (RRR) = 67.8%] and success rate of NGI in accumulative attempts (two attempts maximum) was 88.7% in Group NPA compared with 63.6% in Group O (P = 0.002; ARR = 25.0%, 95% CI = 9.7-40.4%; RRR = 68.9%). Duration for NGI successful at the first attempt in Group NPA was significantly longer than that in Group O (56.3 vs. 27.1 s; P < 0.001; Mean difference = 29.2 s, 95% CI = 20.0-38.4 s). Neither bleeding incidence nor hemodynamic response is significantly different between the two study groups. CONCLUSIONS: The study indicates a preinstalled NPA in the right nasal passageway facilitates NGI in anesthetized and intubated patients as an initial NGI method and as a rescuing method for patients undergoing two unsuccessful initial attempts of NGI without a preinstalled NPA. However, the NPA method proved to take more time than the routine method for NGI successful at the first attempt. TRIAL REGISTRATION: The study was conducted after receiving approval from Institutional Review Board of Chang Gung Memorial Hospital, Linkou branch, Taiwan (registration number 201800138A3; April 11, 2018), and the clinicaltrials.gov (NCT03697642; Principal Investigator: Ting-Yang Huang; Date of registration: October 4, 2018; https://www.clinicaltrials.gov/NCT03697642 ).
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Intubação Gastrointestinal , Intubação Intratraqueal , Anestesia Geral , Humanos , Estudos Prospectivos , TaiwanRESUMO
BACKGROUND: Patients undergoing complex spine surgery present with multilevel spinal involvement, advanced age, and multiple comorbidities. Surgery is associated with significant blood loss and remarkable hemodynamic changes. The present study aimed to investigate the accuracy and trending ability of a non-invasive continuous method to monitor hemoglobin (SpHb) concentrations using a Radical-7™ Pulse CO-Oximeter in complex spine surgery. METHODS: Forty-nine patients who underwent complex spine surgery were enrolled in this prospective observational study. Multiple time points were established for data collection throughout the operation. Simultaneous SpHb-total hemoglobin (tHb) paired data were recorded for analyses. Linear regression analysis, Bland-Altman plot, four-quadrant plot, and Critchley polar plot were used to assess the accuracy and trending ability of the monitor. RESULTS: A total of 272 pairs of SpHb-tHb data were available and were divided into two groups based on the perfusion index (PI): PI values ≥1.0 (n = 200) and PI values < 1.0 (n = 72). The correction coefficients (r) between SpHb and tHb were 0.6946 and 0.6861 in the groups with PI values ≥1.0 and < 1.0, respectively (P < 0000.1). In the ≥1.0 group, the mean bias was - 0.21 g/dL and the percentage error (PE) was 15.85%, whereas in the < 1.0 group, the mean bias was - 0.04 g/dL and the PE was 17.42%. Four-quadrant plot revealed a concordance rate of 85.11%, whereas the Critchley polar plot showed a concordance rate of 67.21%. CONCLUSIONS: The present study demonstrates the acceptable accuracy of the Radical-7™ Pulse CO-Oximeter even with a low PI. However, the trending ability was limited and unsatisfactory.
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Confiabilidade dos Dados , Monitorização Intraoperatória/métodos , Monitorização Fisiológica/métodos , Procedimentos Neurocirúrgicos/métodos , Oximetria/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: During an emergency endotracheal intubation, rapid sequence induction intubation (RSII) with cricoid pressure (CP) is frequently implemented to prevent aspiration pneumonia. We evaluated the CVS in endotracheal intubation in RSII with CP, in comparison with a direct laryngoscope (DL). METHODS: One hundred fifty patients were randomly assigned to one of three groups: the CVS as a video stylet (CVS-V) group, the CVS as a lightwand (CVS-L) group and DL group. Primary outcomes were to assess the power of the CVS, compared with DL, regarding the first attempt success rate and intubation time in simulated RSII with CP. Secondary outcomes were to examine hemodynamic stress response and the incidence of complications. RESULTS: The first attempt success rates within 30 s and within 60 s were higher in CVS-V and DL group than those in CVS-L group (p = 0.006 and 0.037, respectively). The intergroup difference for intubation success rate within 30 s was nonsignificant and almost all the patients were successfully intubated within 60 s (98% for CVS-L and DL group, 96% for CVS-L group). Kaplan-Meier estimator demonstrated the median intubation time was 10.6 s [95% CI, 7.5 to 13.7] in CVS-V group, 14.6 s [95% CI, 11.1 to 18.0] in CVS-L group and 16.5 s [95% CI, 15.7 to 17.3] in DL group (p = 0.023 by the log-rank test). However, the difference was nonsignificant after Sidak's adjustment. The intergroup differences for hemodynamic stress response, sore throat and mucosa injury incidence were also nonsignificant. CONCLUSIONS: The CVS-D and DL provide a higher first attempt intubation success rate within 30 and 60 s in intubation with CP; the intubation time for the CVS-V was nonsignificantly shorter than that for the other two intubation methods. Almost all the patients can be successfully intubated with any of the three intubation methods within 60 s. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03841890 , registered on February 15, 2019 (retrospectively registered).
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Intubação Intratraqueal/métodos , Laringoscópios , Laringoscopia/métodos , Indução e Intubação de Sequência Rápida/métodos , Adulto , Cartilagem Cricoide , Feminino , Humanos , Intubação Intratraqueal/instrumentação , Masculino , Pessoa de Meia-Idade , Pneumonia Aspirativa/prevenção & controle , Pressão , Estudos Prospectivos , Fatores de Tempo , Gravação em VídeoRESUMO
BACKGROUND: The goal of this study was to evaluate the accuracy and interchangeability between continuous cardiac output (CO) measured by electrical velocimetry (COEv) and continuous cardiac output obtained using the pulmonary thermodilution method (COPAC) during living donor liver transplantation (LDLT). METHOD: Twenty-three patients were enrolled in this prospective observational study. CO was recorded by both two methods and compared at nine specific time points. The data were analyzed using correlation coefficients, Bland-Altman analysis for the percentage errors, and the concordance rate for trend analysis using a four-quadrant plot. RESULTS: In total, 207 paired datasets were recorded during LDLT. CO data were in the range of 2.8-12.7 L/min measured by PAC and 3.4-14.9 L/min derived from the EV machine. The correction coefficient between COPAC and COEv was 0.415 with p < 0.01. The 95% limitation agreement was - 5.9 to 3.4 L/min and the percentage error was 60%. The concordance rate was 56.5%. CONCLUSIONS: The Aesculon™ monitor is not yet interchangeable with continuous thermodilution CO monitoring during LDLT. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Chang Gung Medical Foundation in Taiwan (registration number: 201600264B0 ).
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Débito Cardíaco/fisiologia , Transplante de Fígado/métodos , Pulmão/fisiologia , Monitorização Intraoperatória/métodos , Reologia/métodos , Adulto , Idoso , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória/normas , Estudos Prospectivos , Reologia/normas , Termodiluição/métodos , Termodiluição/normasRESUMO
BACKGROUND/PURPOSE: Pulpotomy is the amputation of coronally infected pulp tissue to maintain the vitality and function of the radicular pulp. This study was designed to assess the clinical and radiographic success rates of primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication after a follow-up period of 24 months. METHODS: A retrospective study was conducted by evaluating the success rates of primary molars treated by pulpotomy with diode laser, sodium hypochlorite, or no medication according to the clinical symptoms and signs and radiographic features. RESULTS: There were 145 primary molars included in the study. No significant differences in clinical and radiographic success rates were found among primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication, when the teeth were treated by experienced pedodontists and restored with stainless steel crowns. The 2-year clinical success rates for primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication were all 100%. The 2-year radiographic success rates were 90.9%, 100%, and 87.5% for primary molars treated by pulpotomy using diode laser, sodium hypochlorite, or no medication, respectively. However, when the pulpotomy for primary molars was performed by less-experienced residents, a reduced overall success rate from 94% for attending doctors to 58% for residents was found. CONCLUSION: Operators and final restorations are confounding factors for determining the success rate of primary molars treated by pulpotomy. Pulpotomy with diode laser, sodium hypochlorite, or no medication are all acceptable treatments of choice for coronally infected primary molars.
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Terapia a Laser/métodos , Dente Molar/patologia , Pulpotomia/métodos , Hipoclorito de Sódio/uso terapêutico , Dente Decíduo/patologia , Criança , Pré-Escolar , Fatores de Confusão Epidemiológicos , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: As Chinese Asian populations have an increased risk of intracerebral hemorrhage (ICH) after intravenous tissue plasminogen activator (IV tPA), we aimed to design a rapid, clinically applicable risk scoring system to predict ICH and functional outcomes after IV tPA treatment in Asian ischemic stroke patients. METHODS: From January 2009 to December 2012, consecutive acute ischemic stroke patients treated with IV tPA recruited from the Stroke Registry in Chang Gung Healthcare System (SRICHS) in Taiwan and the National University Hospital of Singapore (NUHS) acute stroke database were used to create and validate a scoring system. Nomogram was created for ICH and 3-month mortality. RESULTS: In total, 932 patients were included in the study: 386 from SRICHS for the derivation of scoring system and 546 from NUHS to validate it. We used nomograms to assign weightage to the scoring system. The presence of atrial fibrillation, glucose level, and the National Institutes of Health Stroke Scale (NIHSS) score were significantly associated with the risk of ICH. Age, NIHSS score, hyperlipidemia, and the presence of post-tPA ICH were significantly associated with mortality. The areas under the curve of derivation and validation cohorts were .663 and .662 for ICH, and .808 and .790 for mortality, respectively. CONCLUSIONS: The scoring system using nomograms can provide a fast, practical, and user-friendly tool that allows physicians to predict the risk of ICH and functional outcomes with IV tPA treatment in a clinical setting.
Assuntos
Povo Asiático , Técnicas de Apoio para a Decisão , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/administração & dosagem , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/induzido quimicamente , Tomada de Decisão Clínica , Bases de Dados Factuais , Feminino , Fibrinolíticos/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Seleção de Pacientes , Valor Preditivo dos Testes , Sistema de Registros , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Singapura/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/etnologia , Acidente Vascular Cerebral/mortalidade , Taiwan/epidemiologia , Terapia Trombolítica/efeitos adversos , Terapia Trombolítica/mortalidade , Ativador de Plasminogênio Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: To investigate if initial blood pressure (BP) on admission is associated with stroke severity and predictive of admission costs and one-year-outcome in acute ischemic (IS) and hemorrhagic stroke (HS). METHODS: This is a single-center retrospective cohort study. Stroke patients admitted within 3 days after onset between January 1st and December 31st in 2009 were recruited. The initial BP on admission was subdivided into high (systolic BP ≥ 211 mmHg or diastolic BP ≥ 111 mmHg), medium (systolic BP 111-210 mmHg or diastolic BP 71-110 mmHg), and low (systolic BP ≤ 110 mmHg or diastolic BP ≤ 70 mmHg) groups and further subgrouped with 25 mmHg difference in systole and 10 mmHg difference in diastole for the correlation analysis with demographics, admission cost and one-year modified Rankin scale (mRS). RESULTS: In 1173 IS patients (mean age: 67.8 ± 12.8 years old, 61.4% male), low diastolic BP group had higher frequency of heart disease (p =0.001), dehydration (p =0.03) and lower hemoglobin level (p <0.001). The extremely high and low systolic BP subgroups had worse National Institutes of Health Stroke Scale (NIHSS) score (p =0.03), higher admission cost (p <0.001), and worse one-year mRS (p =0.03), while extremely high and low diastolic BP subgroups had higher admission cost (p <0.01). In 282 HS patients (mean age: 62.4 ± 15.4 years old, 60.6% male), both low systolic and diastolic BP groups had lower hemoglobin level (systole: p =0.05; diastole: p <0.001). The extremely high and low BP subgroups had worse NIHSS score (p =0.01 and p <0.001, respectively), worse one-year mRS (p =0.002 and p =0.001, respectively), and higher admission cost (diastole: p <0.002). CONCLUSIONS: Stroke patients with extremely high and low BP on admission have not only worse stroke severity but also higher admission cost and/or worse one-year outcome. In those patients with low BP, low admission hemoglobin might be a contributing factor.
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Pressão Sanguínea , Isquemia Encefálica/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Custos e Análise de Custo , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Estados UnidosRESUMO
BACKGROUND: We present a series of patients with blunt abdominal trauma who underwent damage control laparotomy (DCL) and introduce a nomogram that we created to predict survival among these patients. METHODS: This was a retrospective study. From January 2002 to June 2012, 91 patients underwent DCL for hemorrhagic shock. We excluded patients with the following characteristics: a penetrating abdominal injury, age younger than 18 or older than 65 years, a severe or life-threatening brain injury (Abbreviated Injury Scale [AIS] ≥ 4), emergency department (ED) arrival more than 6 hours after injury, pregnancy, end-stage renal disease, or cirrhosis. In addition, we excluded patients who underwent DCL after ICU admission or later in the course of hospitalization. RESULTS: The overall mortality rate was 61.5%: 35 patients survived and 56 died. We identified independent survival predictors, which included a preoperative Glasgow Coma Scale (GCS) score < 8 and a base excess (BE) value < -13.9 mEq/L. We created a nomogram for outcome prediction that included four variables: preoperative GCS, initial BE, preoperative diastolic pressure, and preoperative cardiopulmonary cerebral resuscitation (CPCR). CONCLUSIONS: DCL is a life-saving procedure performed in critical patients, and devastating clinical outcomes can be expected under such dire circumstances as blunt abdominal trauma with exsanguination. The nomogram presented here may provide ED physicians and trauma surgeons with a tool for early stratification and risk evaluation in critical, exsanguinating patients.
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Traumatismos Abdominais/cirurgia , Técnicas de Apoio para a Decisão , Laparotomia , Nomogramas , Choque Hemorrágico/cirurgia , Ferimentos não Penetrantes/cirurgia , Traumatismos Abdominais/complicações , Traumatismos Abdominais/mortalidade , Adolescente , Adulto , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Curva ROC , Estudos Retrospectivos , Medição de Risco , Choque Hemorrágico/etiologia , Choque Hemorrágico/mortalidade , Taxa de Sobrevida , Resultado do Tratamento , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/mortalidade , Adulto JovemRESUMO
BACKGROUND: Liver transplantation is treatment option for patients with end-stage liver disease and hepatocellular carcinoma. Renal function deterioration significantly impacts the survival rates of liver recipients, and serum uric acid (SUA) is associated with both acute and chronic renal function disorders. Thus, our study aimed to assess the relationship and predictive value of preoperative SUA level and postoperative acute kidney injury (AKI) in living donor liver transplantation (LDLT). METHODS: We conducted a prospective observational study on 87 patients undergoing LDLT. Blood samples were collected immediately before LDLT, and renal function status was followed up for 3 consecutive days postoperatively. RESULTS: Low SUA levels (cutoff value 4.15 mg/dL) were associated with a high risk of early posttransplantation AKI. The area under the curve was 0.73 (sensitivity, 79.2%; specificity, 59.4%). Although not statistically significant, there were no deaths in the non-AKI group but two in the early AKI group secondary to liver graft dysfunction in addition to early AKI within the first month after LDLT. CONCLUSION: AKI after liver transplantation may lead to a deterioration of patient status and increased mortality rates. We determined low preoperative SUA levels as a possible risk factor for early postoperative AKI.
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Injúria Renal Aguda , Transplante de Fígado , Doadores Vivos , Ácido Úrico , Humanos , Transplante de Fígado/efeitos adversos , Ácido Úrico/sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologiaRESUMO
Biological drug products are therapeutic moieties manufactured by a living system or organisms. These are important life-saving drug products for patients with unmet medical needs. Because of expensive cost, only a few patients have access to life-saving biological products. Most of the early biological products will lose their patent in the next few years. This provides the opportunity for generic versions of the biological products, referred to as biosimilar drug products. The US Biologic Price Competition and Innovation Act passed in 2009 and the draft guidance issued in 2012 provide an approval pathway for biological products shown to be biosimilar to, or interchangeable with, a Food and Drug Administration-licensed reference biological product. Hence, cost reduction and affordability of the biosimilar products to the average patients may become possible. However, the complexity and heterogeneity of the molecular structures, complicated manufacturing processes, different analytical methods, and possibility of severe immunogenicity reactions make evaluation of equivalence between the biosimilar products and their corresponding reference product a great challenge for statisticians and regulatory agencies. To accommodate the stepwise approach and totality of evidence, we propose to apply a parallel assay to evaluate the extrapolation of the similarity in product characteristics such as doses or pharmacokinetic responses to the similarity in binary efficacy endpoints. We also report the results of simulation studies to evaluate the performance, in terms of size and power, of our proposed methods. We present numerical examples to illustrate the suggested procedures.
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Medicamentos Biossimilares , Técnicas de Química Analítica/métodos , Aprovação de Drogas/métodos , Avaliação de Medicamentos/métodos , Determinação de Ponto Final/métodos , Algoritmos , Produtos Biológicos , Estados Unidos , United States Food and Drug AdministrationRESUMO
For the traditional clinical trials, inclusion and exclusion criteria are usually based on some clinical endpoints; the genetic or genomic variability of the trial participants are not totally utilized in the criteria. After completion of the human genome project, the disease targets at the molecular level can be identified and can be utilized for the treatment of diseases. However, the accuracy of diagnostic devices for identification of such molecular targets is usually not perfect. Some of the patients enrolled in targeted clinical trials with a positive result for the molecular target might not have the specific molecular targets. As a result, the treatment effect may be underestimated in the patient population truly with the molecular target. To resolve this issue, under the exponential distribution, we develop inferential procedures for the treatment effects of the targeted drug based on the censored endpoints in the patients truly with the molecular targets. Under an enrichment design, we propose using the expectation-maximization algorithm in conjunction with the bootstrap technique to incorporate the inaccuracy of the diagnostic device for detection of the molecular targets on the inference of the treatment effects. A simulation study was conducted to empirically investigate the performance of the proposed methods. Simulation results demonstrate that under the exponential distribution, the proposed estimator is nearly unbiased with adequate precision, and the confidence interval can provide adequate coverage probability. In addition, the proposed testing procedure can adequately control the size with sufficient power. On the other hand, when the proportional hazard assumption is violated, additional simulation studies show that the type I error rate is not controlled at the nominal level and is an increasing function of the positive predictive value. A numerical example illustrates the proposed procedures.
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Ensaios Clínicos como Assunto/métodos , Modelos Estatísticos , Projetos de Pesquisa , Algoritmos , Simulação por Computador , Interpretação Estatística de Dados , Determinação de Ponto Final , Humanos , Terapia de Alvo Molecular , Valor Preditivo dos Testes , Probabilidade , Modelos de Riscos ProporcionaisRESUMO
Purpose Intravenous sedation has been well accepted to allow dental restoration in uncooperative children while avoiding aspiration and laryngospasm; however, intravenous anesthetics such as propofol may lead to undesired effects such as respiratory depression and delayed recovery. The use of the bispectral index system (BIS), a monitoring system reflective of the hypnotic state, is con-troversial in the reduction in the risk of respiratory adverse events (RAEs), recovery time, the in-travenous drug dosage, and post-procedural events. The aim of the study is to evaluate whether BIS is advantageous in pediatric dental procedures. Methods A total of 206 cases, aged 2-8 years, receiving dental procedures under deep sedation with propofol using target-controlled infusion (TCI) technique were enrolled in the study. BIS level was not monitored in 93 children whereas it was for 113 children, among which BIS values were maintained between 50-65. Physiological variables and adverse events were recorded. Statistical analysis was conducted using Chi-square, Mann Whitney U, Independent Samples t and Wilcoxon signed tests, with a p value of <0.05 considered to be statistically significant. Results Although no statistical significance in the post-discharge events and total amount of propofol used was observed, a clear significance was identified in periprocedural adverse events (hypoxia, apnea, and recurrent cough, all p value < 0.05) and discharge time (63.4 ± 23.2 vs. 74.5 ± 24.0 min, p value < 0.001) between these two groups. Conclusions The application of BIS in combination with TCI may be beneficial for young children undergoing deep sedation for dental procedures.
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OBJECTIVE: We wanted to examine whether brain computed tomography (CT) perfusion can help to detect the reconstitution of cerebral hemodynamics and predict intracerebral hemorrhage (ICH) after carotid stenting. METHODS: From September 2002 to October 2009, data of 114 patients with carotid intervention were prospectively collected, and we retrospectively identified a total of 108 consecutive patients with unilateral carotid stenting. Brain CT perfusion was studied at three time points: 1 week before, and 1 week and 6 months after stenting. Cerebral blood volume (CBV), cerebral blood flow, and time to peak (TTP) of brain CT perfusion were examined at cortical and subcortical areas of middle cerebral artery (MCA) and posterior cerebral artery territory. The CBV, cerebral blood flow, and TTP ratios of stenting side/nonstenting side were used for comparison. The flow direction of ophthalmic artery was detected by sonography, and the presence of anterior communicating artery was examined on prestenting cerebral angiogram. RESULTS: After carotid stenting, CBV and TTP ratios improved significantly in both MCA cortical and subcortical areas in patients with unilateral carotid stenosis (P < .01) but not in patients with bilateral carotid stenosis. Patients with reversed ophthalmic flow had better improvement of TTP in both MCA and posterior cerebral artery territories (P < .05) than patients with forward flow. However, no significant difference was found between patients with and patients without anterior communicating artery collateral (P > .05). The prestenting TTP ratio in MCA subcortical area was significantly higher in patients with poststenting ICH than patients without ICH (P = .0191). CONCLUSIONS: Cerebral hemodynamics can be reconstituted within a few days after carotid revascularization, especially in patients with reversed ophthalmic flow. Prolonged TTP in prestenting MCA subcortical area may suggest a high risk of poststenting ICH.
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Estenose das Carótidas/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Circulação Cerebrovascular , Hemodinâmica , Neuroimagem , Complicações Pós-Operatórias/diagnóstico por imagem , Stents , Tomografia Computadorizada por Raios X , Idoso , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: We evaluated the effect of neutrophil-to-lymphocyte ratio (NLR) on disease-free survival in patients with stages I to III colorectal cancer (CRC). METHODS: There were 3857 patients identified from our database. We used receiver operating characteristic (ROC) analysis to identify the best cutoff value of NLR. A 5-year disease-free survival was used as end point. Survival analysis was used to assess the NLR effect, after stratification by several clinopathologic factors. RESULTS: In the ROC analysis, NLR = 3 had the highest sensitivity and specificity. Elevated NLR (>3) in colon cancer seemed to accompany larger tumor size (~5 cm) and more advanced T stage. By multivariate analysis, elevated NLR in colon cancer was associated with an increased risk of disease progression or cancer death [hazard ratio (HR) 1.377, 95 % confidence interval 1.104-1.717, P = 0.014]. However, elevated NLR in rectal cancer lost its significance in multivariate analysis (HR 1.121, 95 % confidence interval 0.941-1.336, P = 0.200). Patients with elevated NLR had worse outcome, especially for colon cancer. CONCLUSIONS: Preoperative NLR influenced the disease-free survival in patients with stages I to III CRC. Elevated NLR (>3) was associated with worse outcome (5-year disease-free survival 66.3 % vs. 78.9 % in colon cancer, P < 0.001; 60. 5 % vs. 66.2 % in rectal cancer, P = 0.008). The difference was larger in colon cancer than in rectal cancer. NLR should be considered as a prognostic factor for stages I to III CRC patients after curative surgery.
Assuntos
Neoplasias Colorretais/sangue , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos Eletivos , Linfócitos/patologia , Neutrófilos/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Neoplasias Retais/patologia , Neoplasias Retais/cirurgia , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
Due to increased healthcare expenditure and the need for evidence-supported clinical decision-making, clinical evaluation using comparative effectiveness research (CER) was initially proposed in the US. CER consists of generating and synthesizing evidence in relative benefits, harms, and costs of different alternatives through direct head-to-head comparisons. CER studies can help identify the most effective interventions for patients under specific circumstances, and therefore improve the efficiency of the healthcare system. A Biosignatures project newly launched in Taiwan was inspired by CER, aiming at using discovered biomarkers panel as tools in early detection of disease and prediction of treatment effectiveness.
Assuntos
Biomarcadores/análise , Pesquisa Comparativa da Efetividade , Medicina Baseada em Evidências , Humanos , TaiwanRESUMO
Objectives: To evaluate associations between sarcopenia, type of autoimmune disease and risk of heart failure (HF) and myocardial infarction (MI) in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Methods: In this population-based, cross-sectional study, discharge data from the 2005-2014 US Nationwide Inpatient Sample (NIS) of hospitalized patients with SLE or RA were extracted and analyzed. Univariate and multivariable regression analyses were conducted to determine associations between sarcopenia, type of autoimmune disease and risk of HF/MI. Results: After exclusions, 781,199 hospitalized patients diagnosed with SLE or RA were included. Among the study cohort, 127,812 (16.4%) were hospitalized with HF, and 12,781 (1.6%) were hospitalized with MI. Sarcopenia was found in only 0.1% of HF/MI patients. Logistic regression analyses revealed that sarcopenia was not significantly associated with presence of either HF or MI. Patients with RA had significantly lower odds of HF than SLE patients (aOR = 0.77, 95%CI: 0.76, 0.79) or MI (aOR = 0.86, 95%CI: 0.82, 0.91). Conclusion: In the US, among hospitalized adults diagnosed with SLE or RA, patients with RA are significantly less likely to have HF or MI than those with SLE. Whether sarcopenia leads to increased HF or MI remains inconclusive. Further studies are warranted to investigate the pathophysiology underlying discrepancies between RA and SLE regarding risk for MI or HF.
RESUMO
Background: Adequate pain control is of crucial importance to patient recovery and satisfaction following abdominal surgeries. The optimal analgesia regimen remains controversial in liver resections. Methods: Three groups of patients undergoing open hepatectomies were retrospectively analyzed, reviewing intravenous patient-controlled analgesia (IV-PCA) versus IV-PCA in addition to bilateral rectus sheath and subcostal transversus abdominis plane nerve blocks (IV-PCA + NBs) versus patient-controlled thoracic epidural analgesia (TEA). Patient-reported pain scores and clinical data were extracted and correlated with the method of analgesia. Outcomes included total morphine consumption and numerical rating scale (NRS) at rest and on movement over the first three postoperative days, time to remove the nasogastric tube and urinary catheter, time to commence on fluid and soft diet, and length of hospital stay. Results: The TEA group required less morphine over the first three postoperative days than IV-PCA and IV-PCA + NBs groups (9.21 ± 4.91 mg, 83.53 ± 49.51 mg, and 64.17 ± 31.96 mg, respectively, p < 0.001). Even though no statistical difference was demonstrated in NRS scores on the first three postoperative days at rest and on movement, the IV-PCA group showed delayed removal of urinary catheter (removal on postoperative day 4.93 ± 5.08, 3.87 ± 1.31, and 3.70 ± 1.30, respectively) and prolonged length of hospital stay (discharged on postoperative day 12.71 ± 7.26, 11.79 ± 5.71, and 10.02 ± 4.52, respectively) as compared to IV-PCA + NBs and TEA groups. Conclusions: For postoperative pain management, it is expected that the TEA group required the least amount of opioid; however, IV-PCA + NBs and TEA demonstrated comparable postoperative outcomes, namely, the time to remove nasogastric tube/urinary catheter, to start the diet, and the length of hospital stay. IV-PCA with NBs could thus be a reliable analgesic modality for patients undergoing open liver resections.