RESUMO
Little is known about the incidence of osteoporosis testing and treatment in individuals with schizophrenia, who may be more likely to fracture. Using competing risk models, we found that schizophrenia was associated with lower incidence of testing or treatment. Implications are for understanding barriers and solutions for this disadvantaged group. PURPOSE: Evidence suggests that individuals with schizophrenia may be more likely to experience hip fractures than the general population; however, little is known about osteoporosis management in this disadvantaged subpopulation. Our study objective was to compare bone mineral density (BMD) testing and pharmacologic treatment in hip fracture patients with versus without schizophrenia. METHODS: This was a retrospective population-based cohort study leveraging health administrative databases, and individuals aged 66-105 years with hip fracture between fiscal years 2009 and 2018 in Ontario, Canada. Schizophrenia was ascertained using a validated algorithm. The outcome was a composite measure of (1) pharmacologic prescription for osteoporosis; or (2) a BMD test. Inferential analyses were conducted using Fine-Gray subdistribution hazard regression, with mortality as the competing event. RESULTS: A total of 52,722 individuals aged 66 to 105 years who sustained an index hip fracture in Ontario during the study period were identified, of whom 1890 (3.6%) had schizophrenia. Hip fracture patients with vs without schizophrenia were more likely to be long-term care residents (44.3% vs. 18.1%; standardized difference, 0.59), frail (62.5% vs. 36.5%; standardized difference, 0.54) and without a primary care provider (9.2% vs. 4.8%; standardized difference, 0.18). In Fine-Gray models, schizophrenia was associated with a lower incidence of testing or treatment (0.795 (0.721, 0.877)). CONCLUSIONS: In this population-based retrospective cohort study, a schizophrenia diagnosis among hip fracture patients was associated with a lower incidence of testing or treatment, after accounting for mortality, and several enabling and predisposing factors. Further research is required to investigate barriers to osteoporosis management in this disadvantaged population.
Assuntos
Conservadores da Densidade Óssea , Densidade Óssea , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Esquizofrenia , Humanos , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/fisiopatologia , Fraturas do Quadril/etiologia , Idoso , Ontário/epidemiologia , Estudos Retrospectivos , Feminino , Masculino , Idoso de 80 Anos ou mais , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Fraturas por Osteoporose/etiologia , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Osteoporose/complicações , Densidade Óssea/fisiologia , Esquizofrenia/complicações , Esquizofrenia/epidemiologia , Esquizofrenia/fisiopatologia , Esquizofrenia/tratamento farmacológico , Conservadores da Densidade Óssea/uso terapêutico , Incidência , Absorciometria de Fóton/métodos , Bases de Dados FactuaisRESUMO
In an Ontario fracture liaison service (FLS), we compared medication prescription rates among patients not taking a previously prescribed bone active medication to those with no previous prescription. Prescription rates were similar between these two groups of patients. The FLS provided a secondary opportunity for patients to initiate bone active medication. PURPOSE: We compared bone active medication prescription rates among patients presenting to an Ontario fracture liaison service (FLS) who reported not taking a previously prescribed bone active medication to those with no history of prescription. METHODS: Eligible patients were those screened in 39 fracture clinics between July 1, 2017, and September 15, 2019, who were not taking bone active medication at the time of screening and classified as high risk for future fracture based on CAROC or FRAX. Sociodemographic and clinical risk factor variables were assessed at screening. Bone active medication prescription rate was assessed within 6 months of screening and defined as having received a prescription for the medication from either a specialist or primary care provider. In cases where a specialist report was not available, patient self-reported data were collected. The chi-square test of independence was used to assess differences in prescription rates. RESULTS: Of 17,575 patients screened, eligible patients were 350 with a previous prescription and 2644 without a previous prescription. Compared with patients who reported no previous prescription, those who had a previous prescription were older, more likely to be female and to report a previous fracture, and less likely to smoke. There was no statistically significant difference between the medication prescription rate of patients with a previous prescription (73.7%) compared to patients with no previous prescription (70.7%) (p = 0.157). CONCLUSION: A large jurisdiction-wide FLS approach provided a secondary opportunity to patients who were not taking a previously prescribed bone active medication to initiate that medication.
Assuntos
Conservadores da Densidade Óssea , Osteoporose , Fraturas por Osteoporose , Conservadores da Densidade Óssea/uso terapêutico , Feminino , Humanos , Masculino , Ontário/epidemiologia , Osteoporose/diagnóstico , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Prevenção SecundáriaRESUMO
We examined the demographic characteristics and risk factors of FLS fragility fracture patients who had sustained prior fragility fracture(s) and found that this is an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle. PURPOSE: Our primary objective was to examine whether fragility fracture patients presenting to a provincial fracture liaison service (FLS) having a history of prior fractures, versus those without, differ in demographic characteristics and risk factors for future fracture. A secondary objective was to understand if those who report two or more prior fractures differ from those reporting one prior fracture. METHODS: This cohort study included fragility fracture patients aged 50 + enrolled in the Ontario FLS between July 2017 and September 2019. Patients with versus those without prior fractures were compared on age, sex, index fracture site, biological parents' history of hip fracture, current fracture due to a fall, history of feeling unsteady when walking, history of falls in the past year, smoking, oral steroid use, and comorbid chronic conditions. Pearson's chi-square, Fischer's exact, and analysis of variance tests were used to assess differences. RESULTS: Among 14,454 patients, 16.8% (n = 2428) reported a history of one or more prior fractures after the age of 40. They were significantly more likely to be older, female, with a higher number of comorbidities, with greater incidence of falls, and feel unsteady when walking. Compared to those with one prior fracture, patients with greater than one prior fracture were more likely to report falls in the past year and feel unsteady when walking. CONCLUSION: Findings suggest that FLS fragility fracture patients who had sustained prior fragility fracture are an important high-risk subgroup that warrants further attention within FLS priority pathways in order to disrupt their fragility fracture cycle.
Assuntos
Fraturas do Quadril , Fraturas por Osteoporose , Estudos de Coortes , Feminino , Humanos , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Fatores de Risco , Prevenção SecundáriaRESUMO
Among individuals presenting to an Ontario FLS, we compared bone active medication initiation rates of patients 80 years and older with those 50-79 years old. After accounting for fracture risk status, there was no statistically significant difference in medication initiation rates between the two age groups INTRODUCTION: A Fracture Liaison Service (FLS) offers post-fracture services to individuals over the age of 50 years and could potentially address age inequities in pharmacotherapy often observed for older adults. Among individuals presenting to an Ontario FLS and classified as being at high risk for future fracture, our objective was to compare bone active medication initiation rates of patients 80 years and older with those 50-79 years old. METHODS: In 39 FLS fracture clinics across Ontario, Canada, fracture prevention coordinators identified, assessed, and facilitated the referral of eligible patients for bone densitometry, fracture risk assessment, and implementation of pharmacotherapy in patients classified as high risk for future fracture. Variables assessed at baseline included age, sex, marital status, living location, fracture location, history of previous fracture, parent's history of hip fracture, history of falls, and fracture risk status. At 6 months, bone active medication initiation was assessed in patients classified as high risk for future fracture. The Chi-square test of independence was used to compare medication initiation rates between patients 80 + and those 50-79 years old. RESULTS: Our sample size consisted of 808 patients aged 50-79 years and 346 aged 80 + years. After accounting for fracture risk status, there was no statistically significant difference in medication initiation rates of patients 50-79 and 80 + years old (76.9% versus 73.7%, p = 0.251). CONCLUSION: A systematic approach to identifying patients at high risk for future fracture and tailoring treatment recommendations to these patients appeared to eliminate differences in treatment initiation rates based on older age.
Assuntos
Conservadores da Densidade Óssea , Fraturas do Quadril , Osteoporose , Fraturas por Osteoporose , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade , Ontário/epidemiologia , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Prevenção SecundáriaRESUMO
We examined the impact of fragility fractures on the work outcomes of employed patients. The majority successfully returned to their previous jobs in a short amount of time, and productivity loss at work was low. Our findings underscore the fast recovery rates of working fragility fracture patients. INTRODUCTION: The purpose of this study is to describe the impact of fragility fractures on the work outcomes of patients who were employed at the time of their fracture. METHODS: A self-report anonymous survey was mailed to fragility fracture patients over 50 who were screened as part of the quality assurance programs of fracture clinics across 35 hospitals in Ontario, Canada. Measures of return to work (RTW), at-work productivity loss (Work Limitations Questionnaire), and sociodemographic, fracture-related, and job characteristics were included in the survey. Kaplan-Meier estimates of the cumulative proportion of patients still off work were computed. Factors associated with RTW time following a fragility fracture were examined using Cox proportional hazards modeling. RESULTS: Of 275 participants, 242 (88 %) returned to work. Of these, the median RTW time was 20.5 days. About 86 % returned to the same job, duties, and hours as before their injury. Among full-time workers, the median number of lost hours due to presenteeism was 2.9 h (Q1-Q3 0.4-8.1 h). The median cost of presenteeism was $75.30 based on the month prior to survey completion. In multivariable analyses, female gender, needing surgery, and medium/heavy work requirements were associated with longer RTW time. Earlier RTW time was associated with elbow fracture and feeling completely better at time of survey completion. CONCLUSIONS: The majority of fragility fracture patients successfully returned to their previous jobs in a short amount of time, and productivity loss at work was low. Our findings underscore their fast recovery rates and give reason for optimism regarding the resilience of this population.
Assuntos
Fraturas por Osteoporose/reabilitação , Retorno ao Trabalho , Absenteísmo , Idoso , Eficiência , Emprego/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ontário , Fatores de TempoRESUMO
We evaluated the impact of a more intensive version of an existing post-fracture coordinator-based fracture prevention program and found that the addition of a full-risk assessment improved treatment rates. These findings provide additional support for more intensive programs aimed at reducing the risk of re-fractures. INTRODUCTION: Evidence-based guidelines support coordinator-based programs to improve post-fracture osteoporosis guideline uptake, with more intensive programs including bone mineral density (BMD) testing and/or treatment being associated with better patient outcomes. The purpose of this study was to evaluate the impact of a more intensive version (BMD "fast track") of an existing provincial coordinator-based program. METHODS: We compared two versions of the program that screened treatment naïve fragility fracture patients (>50 years). Cases came from the BMD fast track program that included full fracture risk assessment and communication of relevant guidelines to the primary care provider (PCP). Matched controls were selected from the usual care program matching according to age, sex, fracture type, and date. Two matching techniques were used: traditional (hard) matching (TM) and propensity score matching (PS). The outcomes were treatment initiation with bone sparing medication, BMD testing rate, and the rate of returning to discuss the test results with a PCP. RESULTS: The program improvements led to a significant improvement in treatment initiation within 6 months from 16 % (controls based on PS) or 21 % (controls based on TM) to 32 % (cases). Ninety percent of patients in the BMD fast track program returned to their PCP to discuss bone health in the cases versus 60 % of the controls (for TM and PS). BMD testing occurred in 96 % of cases compared to the 66 (TM) or 65 % (PS) of the matched controls. CONCLUSIONS: Addition of a full-risk assessment to a coordinator-based program significantly improved treatment rates within 6 months of screening.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Osteoporose/diagnóstico , Fraturas por Osteoporose/prevenção & controle , Prevenção Secundária/métodos , Idoso , Densidade Óssea/fisiologia , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoa de Meia-Idade , Ontário/epidemiologia , Osteoporose/tratamento farmacológico , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/fisiopatologia , Guias de Prática Clínica como Assunto , Avaliação de Programas e Projetos de Saúde , Medição de Risco/métodosRESUMO
OBJECTIVES: To determine whether the online patient education material offered by the American College of Cardiology (ACC) and the American Heart Association (AHA) is written at a higher level than the 6th-7th grade level recommended by the National Institute of Health (NIH). METHODS: Online patient education material from each website was subjected to reading grade level (RGL) analysis using the Readability Studio Professional Edition. One-sample t testing was used to compare the mean RGLs obtained from 8 formulas to the NIH-recommended 6.5 grade level and 8th grade national mean. RESULTS: In total, 372 articles from the ACC website and 82 from the AHA were studied. Mean (±SD) RGLs for the 454 articles were 9.6 ± 2.1, 11.2 ± 2.1, 11.9 ± 1.6, 10.8 ± 1.6, 9.7 ± 2.1, 10.8 ± 0.8, 10.5 ± 2.6, and 11.7 ± 3.5 according to the Flesch-Kincaid grade level (FKGL), Simple Measure of Gobbledygook (SMOG Index), Coleman-Liau Index (CLI), Gunning-Fog Index (GFI), New Dale-Chall reading level formula (NDC), FORCAST, Raygor Readability Estimate (RRE), and Fry Graph (Fry), respectively. All analyzed articles had significantly higher RGLs than both the NIH-recommended grade level of 6.5 and the national mean grade level of 8 (p < 0.00625). CONCLUSIONS: Patient education material provided on the ACC and AHA websites is written above the NIH-recommended 6.5 grade level and 8th grade national mean reading level. Additional studies are required to demonstrate whether lowering the RGL of this material improves outcomes among patients with cardiovascular disease.
Assuntos
Letramento em Saúde/estatística & dados numéricos , Educação de Pacientes como Assunto , Leitura , Cardiologia , Compreensão , Humanos , Internet , Sociedades Médicas , Estados UnidosRESUMO
BACKGROUND: Perioperative myocardial infarction or cardiac arrest is associated with significant morbidity and mortality. The Revised Cardiac Risk Index is currently the most commonly used cardiac risk stratification tool; however, it has several limitations, one of which is its relatively low discriminative ability. The objective of the present study was to develop and validate a predictive cardiac risk calculator. METHODS AND RESULTS: Patients who underwent surgery were identified from the American College of Surgeons' 2007 National Surgical Quality Improvement Program database, a multicenter (>250 hospitals) prospective database. Of the 211 410 patients, 1371 (0.65%) developed perioperative myocardial infarction or cardiac arrest. On multivariate logistic regression analysis, 5 predictors of perioperative myocardial infarction or cardiac arrest were identified: type of surgery, dependent functional status, abnormal creatinine, American Society of Anesthesiologists' class, and increasing age. The risk model based on the 2007 data set was subsequently validated on the 2008 data set (n=257 385). The model performance was very similar between the 2007 and 2008 data sets, with C statistics (also known as area under the receiver operating characteristic curve) of 0.884 and 0.874, respectively. Application of the Revised Cardiac Risk Index to the 2008 National Surgical Quality Improvement Program data set yielded a relatively lower C statistic (0.747). The risk model was used to develop an interactive risk calculator. CONCLUSIONS: The cardiac risk calculator provides a risk estimate of perioperative myocardial infarction or cardiac arrest and is anticipated to simplify the informed consent process. Its predictive performance surpasses that of the Revised Cardiac Risk Index.
Assuntos
Algoritmos , Parada Cardíaca/diagnóstico , Modelos Cardiovasculares , Infarto do Miocárdio/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Adulto , Idoso , Feminino , Parada Cardíaca/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Período Perioperatório , Complicações Pós-Operatórias/etiologia , Curva ROC , Medição de Risco/métodosRESUMO
BACKGROUND: The benefit of carotid endarterectomy (CEA) is heavily influenced by the risk of perioperative stroke. Our objective was to use the American College of Surgeons' 2007 and 2008 National Surgical Quality Improvement Program (NSQIP) database to assess the postoperative stroke and death rate after CEA among the more than 180 NSQIP participating hospitals, and to identify the preoperative risk factors. MATERIALS AND METHODS: Univariate analysis included 56 preoperative variables. Outcomes were studied for 30 d. Multivariate logistic regression was used for assessment of risk factors. RESULTS: Of 13,316 patients, 7503 (56.5%) were asymptomatic, while 5770 (43.5%) were symptomatic. Combined stroke or death was seen in 262 patients (2.0%). Postoperative stroke occurred in 186 patients (1.4%). One hundred patients (0.8%) died within 30 d. In asymptomatic and symptomatic patients, stroke or death was seen in 1.3% and 2.9% of patients; stroke in 0.9% and 2% of patients; and death in 0.5% and 1.1% of patients, respectively (all P < 0.001). On multivariate analysis for symptomatic patients, dialysis dependence, chronic open wound, impaired sensorium, and dependent functional status were risk factors for stroke or death (all P < 0.05). Among asymptomatic patients, acute renal failure, corticosteroid use, COPD, paraplegia, and dependent functional status were risk factors for stroke or death (all P < 0.05). CONCLUSIONS: This prospective database confirms that CEA is currently performed with low peri-procedural stroke rate in participating ACS NSQIP hospitals and provides a contemporary framework for comparison of other treatment modalities to CEA. Identification of the above risk factors may help with risk stratification and patient counseling for CEA.
Assuntos
Bases de Dados como Assunto , Endarterectomia das Carótidas/efeitos adversos , Período Perioperatório , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças das Artérias Carótidas/cirurgia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Estados UnidosRESUMO
BACKGROUND AND OBJECTIVES: Outcomes for patients undergoing major pancreatic surgery have improved, but a subset of patients that significantly utilize more resources exists. Variables that can lead to an increase in resource utilization in patients undergoing pancreatic surgery were identified. METHODS: Patients undergoing pancreatic surgery for neoplasms were identified from the NSQIP database (2006-2008). Indices associated with increased resource utilization that we included were operative time (OT), length of stay (LOS), intraoperative RBC transfusion, return to operating room, and occurrence of postoperative complications. Analysis of covariance and multivariable logistic regression were performed. RESULTS: The 4,306 included patients had a median age of 66 years and 50.3% were males. The 30-day morbidity and mortality were 29.3% and 3.2%, respectively. Median OT was 362 min and median LOS was 10 days. Malignancy, neoadjuvant radiation, and medical co-morbidities were associated with increased OT (P < 0.0001 for all). Declining preoperative functional status was the most important predictor of LOS (P < 0.0001). Age, male gender, hypertension, severe COPD, and higher BMI were significantly associated with postoperative complications (P < 0.050 for all). CONCLUSIONS: Morbidity after pancreatic surgery remains high. Age, obesity, performance status, medical co-morbidities, and neoadjuvant radiation affect outcomes and may lead to increased use of hospital resources.
Assuntos
Recursos em Saúde/estatística & dados numéricos , Hospitais/estatística & dados numéricos , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Complicações Pós-Operatórias , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Comorbidade , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Outcomes for patients who undergo laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery have improved, but a subset of patients who significantly utilize more resources exists. We identified preoperative variables that increase resource utilization in patients who undergo LRYGB. METHODS: Patients who underwent LRYGB in 2007 and 2008 were identified from the NSQIP database. Variables that indicated resource utilization were operative time (OT), length of stay (LOS), and occurrence of postoperative complications. Analyses were performed by using multivariate analysis of variance and logistic regression. RESULTS: Of 14,251 patients with a mean age of 44.6 (± 11.1) years, 19.4% were men. The national 30-day morbidity and mortality were 4.5% and 0.17%, respectively. The median OT was 128 min (interquartile range (IQR), 100-167), and the median LOS was 2 days (IQR, 2-3). Bleeding disorder, male gender, African American race, increasing weight, and age were significantly associated with increased OT (p < 0.05 for all). Severe chronic obstructive pulmonary disease, bleeding disorder, increasing age, and anesthesia time were associated with increased length of stay (p < 0.05). Preoperative dialysis dependence (odds ratio (OR), 8.5; 95% confidence interval (CI), 2.3-32.3) and dyspnea at rest (OR, 3.3; 95% CI, 1.7-6.3) were the greatest predictors of postoperative complications. Emergency case, bleeding disorder, prior percutaneous coronary intervention, and increasing operative time also were significantly associated with increased postoperative complications on multivariate logistic regression analysis (p < 0.05 for all). CONCLUSIONS: Age, sex, race, obesity, and some medical comorbidities affect outcomes and increase resource utilization. Optimization of modifiable factors and careful patient selection are needed to facilitate further improvement in outcomes and resource utilization.
Assuntos
Derivação Gástrica/métodos , Recursos em Saúde/estatística & dados numéricos , Laparoscopia , Adulto , Feminino , Humanos , Masculino , Análise Multivariada , Resultado do TratamentoRESUMO
Palmar-plantar erythrodysesthesia (PPE), more commonly known as hand-foot syndrome, is a dermatologic complication following chemotherapy with selective agents. In this article, we present the case of a young lady with stage III breast cancer who developed palmar-plantar erythrodysesthesia following treatment with Herceptin (trastuzumab), an unusual complication of this particular drug. From our review of literature, this is the second known occurrence of PPE secondary to trastuzumab monotherapy.
RESUMO
UNLABELLED: To review 20 years of literature on chronic mesenteric ischemia (CMI), examining its complex clinical presentation and comparing open and endovascular treatment options. METHODS: The PubMed and EBSCOHost electronic databases were queried to identify English-language articles published over the last 20 years. Scrutiny of the retrieved articles identified 1939 patients (mean age 65 years). Of these, 1163 patients underwent open surgery: 714 between 2000 and 2009 and 449 between 1990 and 1999. Of the 776 patients undergoing endovascular repairs, the majority (684) were performed between 2000 and 2009; 92 patients were treated between 1990 and 1999. Data were entered in an electronic database and were pooled for categorical analysis. RESULTS: No major differences were seen among open surgeries or among endovascular surgeries performed when comparing the 2 time periods. On comparing open and endovascular surgeries performed between 2000 and 2009, symptom improvement was 2.4 times more likely after open compared to endovascular surgery (95% CI 1.5 to 3.6, p<0.001). Five-year primary patency and 5-year assisted primary patency were 3.8 (95% CI 2.4 to 5.8, p<0.001) and 6.4 (95% CI 1.3 to 30.1, p = 0.02) times greater in the open group. Freedom from symptoms at 5 years was 4.4 times greater for open versus endovascular (95% CI 2.8 to 7.0, p<0.001). The complication rate for open versus endovascular surgery was 3.2 times greater (95% CI 2.5 to 4.2, p<0.001). The difference in mortality was not statistically significant (p = 0.75). CONCLUSION: Our data demonstrate that open revascularization surpasses endovascular procedures in long-term vessel patency and control of symptoms. Patients undergoing open procedures do, however, develop increased complications perioperatively. The preferred revascularization approach used in treating this condition should be tailored to the anatomy and physiology of each patient.
Assuntos
Implante de Prótese Vascular , Isquemia/cirurgia , Oclusão Vascular Mesentérica/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Doença Crônica , Humanos , Isquemia/etiologia , Isquemia/mortalidade , Isquemia/fisiopatologia , Oclusão Vascular Mesentérica/complicações , Oclusão Vascular Mesentérica/mortalidade , Oclusão Vascular Mesentérica/fisiopatologia , Pessoa de Meia-Idade , Razão de Chances , Seleção de Pacientes , Reoperação , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução Vascular , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
The hypoxia-regulated tumor-suppressor von Hippel-Lindau (VHL) is an E3 ligase that recognizes its substrates as part of an oxygen-dependent prolyl hydroxylase (PHD) reaction, with hypoxia-inducible factor α (HIFα) being its most notable substrate. Here we report that VHL has an equally important function distinct from its hypoxia-regulated activity. We find that Aurora kinase A (AURKA) is a novel, hypoxia-independent target for VHL ubiquitination. In contrast to its hypoxia-regulated activity, VHL mono-, rather than poly-ubiquitinates AURKA, in a PHD-independent reaction targeting AURKA for degradation in quiescent cells, where degradation of AURKA is required to maintain the primary cilium. Tumor-associated variants of VHL differentiate between these two functions, as a pathogenic VHL mutant that retains intrinsic ability to ubiquitinate HIFα is unable to ubiquitinate AURKA. Together, these data identify VHL as an E3 ligase with important cellular functions under both normoxic and hypoxic conditions.
Assuntos
Aurora Quinase A/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo , Carcinoma de Células Renais/genética , Hipóxia Celular , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/genética , Mutação , Ubiquitinação , Proteína Supressora de Tumor Von Hippel-Lindau/genéticaRESUMO
In this study we examined the changes in alpha and LH beta mRNAs in anterior pituitaries of male and female rats after castration. mRNA concentrations were measured by an optimized RNA dot blot hybridization assay. Rat alpha and LH beta cDNAs were nick-translated to specific activities of 2-5 X 10(8) cpm/micrograms and were used as hybridization probes. The total RNA per assay, RNA per dot, and saturating amounts of probe were optimized. The intra- and interassay coefficients of variation were 5% and 28%, respectively. Both alpha and LH beta mRNA concentrations increased after castration, but marked differences were observed in the kinetics of responses in male and female rats. In males, alpha and LH beta mRNAs were increased by 24 h postcastration (by 25% and 38%, respectively), and 4- to 5-fold increases over intact controls were evident by 18 days. Alpha mRNA rose rapidly and had doubled by 2 days, whereas LH beta mRNA concentrations showed a similar increase by 6-7 days postcastration. The slower rise in LH beta mRNA was associated with a transient decline in serum and pituitary LH concentrations between 2 and 6 days after castration. In female rats, alpha mRNA increased more slowly. Alpha concentrations had doubled by 10 days, while a similar increase in LH beta mRNA occurred 7 days after castration. Thereafter, both subunit mRNAs continued to rise, and by day 20 alpha mRNA was increased 5-fold and LH beta mRNA 16-fold over values in intact females. Serum and pituitary LH concentrations rose gradually, and both were increased by 7-10 days after castration. The increase in serum and pituitary LH followed a time course similar to that of the progressive rise in LH beta mRNA concentrations. These data show that an increase in steady state LH subunit mRNA concentrations is one of the mechanisms involved in increased gonadotropin biosynthesis and secretion after castration. The kinetics of LH subunit mRNA and LH secretory responses are different in male and female rats and suggest that the concentration of LH beta mRNA may be a limiting factor in LH secretion.
Assuntos
Castração , Hormônio Luteinizante/genética , Fragmentos de Peptídeos/genética , Adeno-Hipófise/metabolismo , Hormônios Adeno-Hipofisários/genética , RNA Mensageiro/metabolismo , Animais , DNA/genética , Feminino , Subunidade alfa de Hormônios Glicoproteicos , Cinética , Masculino , Hibridização de Ácido Nucleico , Ratos , Fatores SexuaisRESUMO
Immediate sealing of furcation perforations enhances the repair process. The purpose of this study was to longitudinally compare the ability of mineral trioxide aggregate (MTA) and Super-EBA to seal furcation perforations. Fifty-one extracted human maxillary molars were decoronated 3 mm above the CEJ, and the roots were amputated 3 mm below the furcation. A #2 high-speed round bur was used to perforate the center of the furcations. The canals were obturated with gutta-percha, and the root ends were sealed with C&B Metabond. Three experimental groups of 15 teeth each were restored with MTA, Super-EBA, or a combination of MTA in the perforation and a Super-EBA dome on the pulpal floor. Six teeth served as controls. Each tooth was affixed to a fluid filtration device and subjected to a pressure of 20 cm H2O. The integrity of the perforation seal was evaluated initially at 30 min for the Super-EBA and the combination groups and at 4 h for the MTA group. Additional measurements were then made at 24 h, 1 week, and 1 month. The controls behaved as expected. A two-way ANOVA revealed a significant difference (p = 0.01) between materials. Tukey's test isolated the difference to Super EBA as producing a superior seal but only at 24 h. There was no significant effect with time (p = 0.57) or the interaction of the materials with time (p = 0.66). All materials sealed the perforations very well. The maximum leakage of all materials was <0.007 microL min(-1) cm H2O(-1).
Assuntos
Compostos de Alumínio/uso terapêutico , Compostos de Cálcio/uso terapêutico , Cimentos Dentários/uso terapêutico , Infiltração Dentária/prevenção & controle , Adesivos Dentinários/uso terapêutico , Defeitos da Furca/terapia , Óxidos/uso terapêutico , Silicatos/uso terapêutico , Raiz Dentária/lesões , Análise de Variância , Combinação de Medicamentos , Humanos , Pressão Hidrostática , Estudos Longitudinais , Dente Molar , Distribuição Aleatória , Estatísticas não ParamétricasRESUMO
Microscopic examination, particularly by scanning electron microscopy, of the tunica intima of the pulmonary arteries of dogs experimentally infected with a known number of larvae of Dirofilaria immitis revealed various numbers and shapes of intimal thickenings. The number and morphology of these thickenings were related to the degree of infection. At 11 months after infection, dogs having adult worm populations of 8 to 21 worms had scattered discrete intimal lesions, whereas in dogs with 41 to 68 adult worms, the intima was diffusely affected. Discrete lesions took the form of rugous or verrucous protrusions, and in severely affected animals, the intima was extensively covered with anatomosing ridges. Light microscopy and transmission electron microscopy confirmed earlier reports that the thickenings were mainly confined to the tunica intima, that the surface was covered by endothelium, and that many of the cells in the intimal swellings were derived from smooth muscle.
Assuntos
Dirofilariose/veterinária , Doenças do Cão/patologia , Artéria Pulmonar/ultraestrutura , Animais , Dirofilariose/patologia , Cães , Feminino , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de VarreduraRESUMO
OBJECTIVE: To identify preoperative factors associated with an increased risk of postoperative pneumonia and subsequently develop and validate a risk calculator. PATIENTS AND METHODS: The American College of Surgeons' National Surgical Quality Improvement Program, a multicenter, prospective data set (2007-2008) was used. Univariate and multivariate logistic regression analyses were performed. The 2007 data set (N=211,410) served as the training set, and the 2008 data set (N=257,385) served as the validation set. RESULTS: In the training set, 3825 patients (1.8%) experienced postoperative pneumonia. Patients who experienced postoperative pneumonia had a significantly higher 30-day mortality (17.0% vs 1.5%; P<.001). On multivariate logistic regression analysis, 7 preoperative predictors of postoperative pneumonia were identified: age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The risk model based on the training data set was subsequently validated on the validation data set, with model performance being very similar (C statistic: 0.860 and 0.855, respectively). The high C statistic indicates excellent predictive performance. The risk model was used to develop an interactive risk calculator. CONCLUSION: Preoperative variables associated with an increased risk of postoperative pneumonia include age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The validated risk calculator provides a risk estimate for postoperative pneumonia and is anticipated to aid in surgical decision making and informed patient consent.
Assuntos
Pneumonia/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Medição de Risco/métodos , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pneumonia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Período Pré-Operatório , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de RiscoRESUMO
BACKGROUND: Postoperative pneumonia (PP) and respiratory failure (PRF) are known to be the most common nonwound complications after bariatric surgery. Our objective was to identify their current prevalence after bariatric surgery and to study the preoperative factors associated with them using data from the American College of Surgeons' National Surgical Quality Improvement Program. METHODS: Patients undergoing bariatric surgery were identified from the National Surgical Quality Improvement Program (2006-2008), a multicenter, prospective database. Univariate analysis and multivariate logistic regression analysis were performed. RESULTS: Of 32,889 patients, PP was diagnosed in 187 patients (.6%) and PRF in 204 patients (.6%). The overall 30-day morbidity rate was 6.4%, with PP and PRF accounting for 18.7%. The 30-day mortality rate was greater for the patients with PP and PRF than those without (4.3% versus .16% and 13.7% versus .10%, P < .0001). The hospital length of stay was also longer in patients with PP/PRF (P < .0001). On multivariate analysis, congestive heart failure (odds ratio 5.3, 95% confidence interval 1.20-23.26) and stroke (odds ratio 4.1, 95% confidence interval 1.42-11.49) were the greatest preoperative risk factors for PP. Previous percutaneous coronary intervention (odds ratio 2.8, 95% confidence interval 1.64-4.74) and dyspnea at rest (odds ratio 2.64, 95% confidence interval 1.13-6.13) were the factors most strongly associated with PRF. Bleeding disorder, age, chronic obstructive pulmonary disease, and type of surgery were risk factors for both (P < .05). Smoking also predisposed to PP, and diabetes mellitus, anesthesia time, and increasing weight also predisposed to PRF (P < .05 for all). CONCLUSION: Although PP and PRF are infrequent, they account for one fifth of the postoperative morbidity and are associated with significantly increased 30-day mortality. They can be predicted by various risk factors, emphasizing the importance of patient optimization and careful selection before bariatric surgery.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Obesidade Mórbida/cirurgia , Pneumonia/etiologia , Insuficiência Respiratória/etiologia , Adulto , Análise de Variância , Feminino , Humanos , Intubação , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pneumonia/epidemiologia , Cuidados Pré-Operatórios , Prevalência , Prognóstico , Estudos Prospectivos , Insuficiência Respiratória/epidemiologia , Retratamento , Fatores de Risco , Desmame do RespiradorRESUMO
BACKGROUND: Although a risk score estimating postoperative mortality for patients undergoing gastric bypass exists, there is none predicting postoperative morbidity. Our objective was to develop a validated risk calculator for 30-day postoperative morbidity of bariatric surgery patients. STUDY DESIGN: We used the American College of Surgeons' 2007 National Surgical Quality Improvement Program (NSQIP) dataset. Patients undergoing bariatric surgery for morbid obesity were studied. Multiple logistic regression analysis was performed and a risk calculator was created. The 2008 NSQIP dataset was used for its validation. RESULTS: In 11,023 patients, mean age was 44.6 years, 20% were male, 77% were Caucasian, and mean body mass index (BMI; calculated as kg/m(2)) was 48.9. Thirty-day morbidity and mortality were 4.2% and 0.2%, respectively. Risk factors associated with increased risk of postoperative morbidity included recent MI/angina (odds ratio [OR] = 3.65; 95% CI 1.23 to 10.8), dependent functional status (OR = 3.48; 95% CI 1.78 to -6.80), stroke (OR = 2.89; 95% CI 1.09 to 7.67), bleeding disorder (OR = 2.23; 95% CI 1.47 to 3.38), hypertension (OR = 1.34; 95% CI 1.10 to 1.63), BMI, and type of bariatric surgery. Patients with BMI 35 to <45 and >60 had significantly higher adjusted OR compared with patients with BMI of 45 to 60 (p < 0.05 for all). These factors were used to create the risk calculator and subsequently validate it, with the model performance very similar between the 2007 training dataset and the 2008 validation dataset (c-statistics: 0.69 and 0.66, respectively). CONCLUSIONS: NSQIP data can be used to develop and validate a risk calculator that predicts postoperative morbidity after various bariatric procedures. The risk calculator is anticipated to aid in surgical decision making, informed patient consent, and risk reduction.