RESUMO
PURPOSE: To evaluate the effect of intravitreal aflibercept injection on visual function in wet age-related macular degeneration (AMD). DESIGN: Prospective, multicenter, double-masked, active-controlled, parallel-group, randomized phase 3 clinical studies (VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet AMD [VIEW] 1 and 2 [clinicaltrials.gov identifiers, NCT00509795 and NCT00637377, respectively]). PARTICIPANTS: Patients (n=2419) with active, treatment-naïve, exudative AMD. This analysis included patients who received intravitreal aflibercept 2.0 mg every 8 weeks (2q8; n=607) or ranibizumab 0.5 mg every 4 weeks (0.5q4; n=595). INTERVENTION: Patients were randomized 1:1:1:1 to receive intravitreal aflibercept 2q8 (after 3 initial monthly doses), intravitreal aflibercept 2q4, intravitreal aflibercept 0.5q4, or ranibizumab 0.5q4 in the study eye. Patients in the intravitreal aflibercept 2q8 group received a sham injection alternating with active treatment. MAIN OUTCOME MEASURES: The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was administered at baseline and at weeks 12, 24, 36, and 52. The NEI VFQ-25 subscale scores were compared between intravitreal aflibercept 2q8 and ranibizumab 0.5q4 treatment arms, the approved dosing for each agent worldwide. Change in composite NEI VFQ-25 score was evaluated based on categorical change in visual acuity (worsened, unchanged, improved). RESULTS: Baseline NEI VFQ-25 scores were similar for both treatments in both studies. Mean change from baseline to 52 weeks was similar for ranibizumab 0.5q4 and intravitreal aflibercept 2q8 across all 12 subscales, with the greatest improvements noted for mental health and general vision (9.0-11.6 points, both treatments, both studies). Improvement of 4 points or more (both treatments, both studies) also was observed for subscales near vision, distance vision, role difficulties, and dependency. Mean change from baseline to 52 weeks in NEI VFQ-25 composite score (pooled data) stratified by clinical response showed meaningful improvement only in patients who gained 5 Early Treatment Diabetic Retinopathy letters or more (7.3 and 7.8 points for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, respectively). CONCLUSIONS: Visual function outcomes were similar across all NEI VFQ-25 subscales over 52 weeks for intravitreal aflibercept 2q8 and ranibizumab 0.5q4, with clinically meaningful improvement recorded in 6 of 12 subscales.
Assuntos
Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Degeneração Macular Exsudativa/tratamento farmacológico , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Injeções Intravítreas , Masculino , Estudos Prospectivos , Ranibizumab , Perfil de Impacto da Doença , Inquéritos e Questionários , Degeneração Macular Exsudativa/fisiopatologiaRESUMO
In celebrating the 60th anniversary of the first isolation of human cytomegalovirus (HCMV), we reflect on the merits and limitations of the viral strains currently being used to develop urgently needed treatments. HCMV research has been dependent for decades on the high-passage strains AD169 and Towne, heavily exploiting their capacity to replicate efficiently in fibroblasts. However, the genetic integrity of these strains is so severely compromised that great caution needs to be exercised when considering their past and future use. It is now evident that wild-type HCMV strains are not readily propagated in vitro. HCMV mutants are rapidly selected during isolation in fibroblasts, reproducibly affecting gene RL13, the UL128 locus (which includes genes UL128, UL130 and UL131A) and often the U(L)/b' region. As a result, the virus becomes less cell associated, altered in tropism and less pathogenic. This problem is not restricted to high-passage strains, as even low-passage strains can harbour biologically significant mutations. Cloning and manipulation of the HCMV genome as a bacterial artificial chromosome (BAC) offers a means of working with stable, genetically defined strains. To this end, the low-passage strain Merlin genome was cloned as a BAC and sequentially repaired to match the viral sequence in the original clinical sample from which Merlin was derived. Restoration of UL128L to wild type was detrimental to growth in fibroblasts, whereas restoration of RL13 impaired growth in all cell types tested. Stable propagation of phenotypically wild-type virus could be achieved only by placing both regions under conditional expression. In addition to the development of these tools, the Merlin transcriptome and proteome have been characterized in unparalleled detail. Although Merlin may be representative of the clinical agent, high-throughput whole-genome deep sequencing studies have highlighted the remarkable high level of interstrain variation present in circulating virus. There is a need to develop systems capable of addressing the significance of this diversity, free from the confounding effects of genetic changes associated with in vitro adaptation. The generation of a set of BAC clones, each containing the genome of a different HCMV strain repaired to match the sequence in the clinical sample, would provide a pathway to address the biological and clinical effects of natural variation in wild-type HCMV.
Assuntos
Infecções por Citomegalovirus/imunologia , Infecções por Citomegalovirus/virologia , Citomegalovirus/fisiologia , Animais , Citomegalovirus/classificação , Evolução Molecular , Regulação Viral da Expressão Gênica , Genes Virais , Variação Genética , Genoma Viral , Humanos , Mutação , Seleção Genética , Biologia de SistemasRESUMO
BACKGROUND AND OBJECTIVES: Recommendations to refer pancreatic procedures to high-volume centers have been in place for a decade. We sought to determine whether regionalization of pancreatic procedures to high-volume centers is occurring in Illinois. METHODS: We compared pancreatic procedures performed in Illinois hospitals from 2000 to 2004 [time period (TP) 1] versus 2005-2009 (TP2) for changes in inpatient mortality and hospital volume. Hospitals were categorized into low- (LVH), intermediate- (IVH), or high-volume (HVH). RESULTS: From TP1 to TP2, there was a 23% increase in absolute case volume (2,232-2,737), despite fewer hospitals performing pancreatic procedures (114-95). In hospital mortality decreased (5.5-3.3%, P < 0.01) and was lowest at HVHs. LVHs and IVHs were associated with a 4.7 and 3.0 higher odds of mortality, respectively (both P < 0.001). Overall, HVHs performed 659 (+73%) more procedures, whereas cumulative procedure volume dropped by 154 cases at LVHs (+1%) and IVHs (-18%). CONCLUSIONS: We observed limited evidence of regionalization of pancreatic procedures in Illinois. The increase in HVH case volume cannot be solely attributed to regionalization, given the corresponding modest decrease seen at non-HVHs. There is opportunity for Illinois hospitals to implement strategies such as selective referral to improve mortality after pancreatic resection.
Assuntos
Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Pâncreas/cirurgia , Pancreatectomia , Pancreatopatias/cirurgia , Encaminhamento e Consulta , Adulto , Idoso , Análise de Variância , Comorbidade , Feminino , Mortalidade Hospitalar , Humanos , Illinois/epidemiologia , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Pancreatectomia/mortalidade , Pancreatectomia/normas , Pancreatectomia/estatística & dados numéricos , Pancreatectomia/tendências , Neoplasias Pancreáticas/cirurgia , Encaminhamento e Consulta/normas , Encaminhamento e Consulta/tendênciasRESUMO
The recommended dose of IgG in primary immunodeficiency (PID) has been increasing since its first use. This study aimed to determine if higher subcutaneous IgG doses resulted in improved patient outcomes by comparing results from two parallel clinical studies with similar design. One patient cohort received subcutaneous IgG doses that were 1.5 times higher than their previous intravenous doses (mean 213 mg/kg/week), whereas the other cohort received doses identical to previous subcutaneous or intravenous doses (mean 120 mg/kg/week). While neither cohort had any serious infections, the cohort maintained on higher mean IgG dose had significantly lower rates of non-serious infections (2.76 vs. 5.18 episodes/year, P < 0.0001), hospitalization (0.20 vs. 3.48 days/year, P < 0.0001), antibiotic use (48.50 vs. 72.75 days/year, P < 0.001), and missed work/school activity (2.10 vs. 8.00 days/year, P < 0.001). The higher-dose cohort had lower health care utilization and improved indices of well being compared to the cohort treated with traditional IgG doses.
Assuntos
Imunoglobulina G/uso terapêutico , Síndromes de Imunodeficiência/terapia , Administração Cutânea , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Hospitalização , Humanos , Imunoglobulina G/administração & dosagem , Síndromes de Imunodeficiência/complicações , Infecções/etiologia , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND AIM OF THE STUDY: Current guidelines suggest that the use of a mechanical prosthesis is favored when patients are already receiving long-term anticoagulation for conditions such as atrial fibrillation (AF). Surgical AF ablation can restore normal sinus rhythm (NSR) and obviate the need for anticoagulation. The study aim was to determine the impact of concomitant AF ablation in patients with AF undergoing aortic valve replacement (AVR) on the restoration of NSR and subsequent requirement for anticoagulation. METHODS: Between April 2004 and December 2009, a total of 124 patients (mean age 74 +/- 12 years) with pre-existing AF underwent AVR with or without coronary artery bypass grafting. The documented preoperative rhythm was long-standing persistent AF in 39 patients (32%), persistent AF in five (4%), and paroxysmal AF in 80 (65%). Eighty patients (65%) had concomitant surgical AF ablation. In the ablation group, bilateral pulmonary vein isolation was performed in 55 cases (69%), left atrial-maze in 15 (19%), and Cox-maze in 10 (13%). A left atrial appendage closure was performed in 70 patients (88%). Sinus rhythm, in addition to anti-arrhythmic and warfarin use, were assessed between three and 15 months after surgery. Postoperatively, 13 patients died and 18 were lost to follow up during the three- to 15-month window; consequently, 71 patients were available for analysis in the ablation group, and 22 in the non-ablation group. RESULTS: In-hospital mortality was 4% (the Ambler score predicted a median (IQR) of 6 (4-9)%). Freedom from AF when not receiving anti-arrhythmic drugs (AADs) occurred in 58 patients (82%) in the ablation group, compared to eight (36%) in the non-ablation group (p < 0.001). Fifty patients (70%) were free from warfarin in the ablation group, compared to six (27%) in the non-ablation group (p < 0.001). No differences were identified in freedom from AF between the surgical AF lesion sets. AF ablation, younger age, and paroxysmal AF were independently associated with freedom from AF when not receiving AADs. CONCLUSION: Surgical AF ablation is associated with an improved restoration of NSR in patients with AF requiring AVR. The need for anticoagulation is reduced in the majority of patients. A bioprosthetic valve may be an acceptable option for a patient with AF who requires AVR.
Assuntos
Anticoagulantes/uso terapêutico , Valva Aórtica/cirurgia , Fibrilação Atrial , Ablação por Cateter , Doenças das Valvas Cardíacas , Implante de Prótese de Valva Cardíaca , Isquemia Miocárdica , Idoso , Idoso de 80 Anos ou mais , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/terapia , Ablação por Cateter/métodos , Ablação por Cateter/estatística & dados numéricos , Comorbidade , Ponte de Artéria Coronária/métodos , Ponte de Artéria Coronária/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Doenças das Valvas Cardíacas/epidemiologia , Doenças das Valvas Cardíacas/terapia , Implante de Prótese de Valva Cardíaca/métodos , Implante de Prótese de Valva Cardíaca/estatística & dados numéricos , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/terapia , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Hyperspectral imaging is a novel technology that can noninvasively measure oxyhemoglobin and deoxyhemoglobin concentrations to create an anatomic oxygenation map. It has predicted healing of diabetic foot ulcers; however, its ability to assess peripheral arterial disease (PAD) has not been studied. The aims of this study were to determine if hyperspectral imaging could accurately assess the presence or absence of PAD and accurately predict PAD severity. METHODS: This prospective study included consecutive consenting patients presenting to the vascular laboratory at the Jesse Brown VA Medical Center during a 10-week period for a lower extremity arterial study, including ankle-brachial index (ABI) and Doppler waveforms. Patients with lower extremity edema were excluded. Patients underwent hyperspectral imaging at nine angiosomes on each extremity. Additional sites were imaged when tissue loss was present. Medical records of enrolled patients were reviewed for demographic data, active medications, surgical history, and other information pertinent to PAD. Patients were separated into no-PAD and PAD groups. Differences in hyperspectral values between the groups were evaluated using the two-tailed t test. Analysis for differences in values over varying severities of PAD, as defined by triphasic, biphasic, or monophasic Doppler waveforms, was conducted using one-way analysis of variance. Hyperspectral values were correlated with the ABI using a Pearson bivariate linear correlation test. RESULTS: The study enrolled 126 patients (252 limbs). After exclusion of 15 patients, 111 patients were left for analysis, including 46 (92 limbs) no-PAD patients and 65 (130 limbs) PAD patients. Groups differed in age, diabetes, coronary artery disease, congestive heart failure, tobacco use, and insulin use. Deoxyhemoglobin values for the plantar metatarsal, arch, and heel angiosomes were significantly different between patients with and without PAD (P < .005). Mean deoxyhemoglobin values for the same three angiosomes showed significant differences between patients with monophasic, biphasic, and triphasic waveforms (P < .05). In patients with PAD, there was also significant correlation between deoxyhemoglobin values and ABI for the same three angiosomes (P = .001). Oxyhemoglobin values did not predict the presence or absence of PAD, did not correlate with PAD severity, and did not correlate with the ABI. CONCLUSIONS: These results suggest the ability of hyperspectral imaging to detect the presence of PAD. Hyperspectral measurements can also evaluate different severities of PAD.
Assuntos
Hemoglobinas/metabolismo , Oxiemoglobinas/metabolismo , Doença Arterial Periférica/diagnóstico , Análise Espectral , Idoso , Estudos de Coortes , Feminino , Humanos , Extremidade Inferior/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/metabolismo , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Análise Espectral/instrumentaçãoRESUMO
BACKGROUND: An abnormally elevated preoperative white blood cell count (WBC) has been associated with postoperative morbidity and mortality. However, it is unknown if a normal WBC is predictive of postoperative outcomes following vascular interventions. Thus, the objective of this study is to determine if a WBC within the normal range is predictive of outcomes following vascular interventions. METHODS: The medical records of patients undergoing endovascular and open repair of carotid stenosis, aortic aneurysm, and peripheral arterial disease from 1999 to 2009 were retrospectively reviewed. Major adverse events (MAE) were defined as death, stroke, and myocardial infarction. RESULTS: Of 1773 cases with normal preoperative WBC (3.5-10.5 K/µL), there were 804 [45.3%] endovascular and 969 [54.7%] open vascular surgeries. Patients with complications (55) or MAE (19) after endovascular intervention had higher preoperative WBC compared with patients without complications (WBC 7.7 ± 1.47 vs 7.1 ± 1.57, respectively, P = .002) or MAE (WBC 8.3 ± 1.26 vs 7.1 ± 0.06, respectively, P = .001). No difference was observed for patients who received open surgery. Patients undergoing endovascular intervention were 2.3, 4.8, and 22 times more likely to experience complications (P = .004), MAE (P = .003), or death (P = .036) when WBC exceeded 7.5 K/µL. Multivariate analysis showed that preoperative normal WBC was an independent predictor of complications, MAE, and death in patients after endovascular procedures but only for death in patients after open vascular procedures. CONCLUSIONS: This study demonstrates a strong linear correlation between an increasing preoperative WBC within the normal range and an increased risk for postoperative complications and death following endovascular interventions. The study also found a significant curvilinear U-shaped relation between a normal preoperative WBC and death in the open surgical cohort, with patients in the very low and very high normal WBC range at an increased risk of death.
Assuntos
Aneurisma Aórtico/cirurgia , Estenose das Carótidas/cirurgia , Procedimentos Endovasculares , Contagem de Leucócitos , Doença Arterial Periférica/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aneurisma Aórtico/sangue , Aneurisma Aórtico/mortalidade , Estenose das Carótidas/sangue , Estenose das Carótidas/mortalidade , Distribuição de Qui-Quadrado , Chicago , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/etiologia , Doença Arterial Periférica/sangue , Doença Arterial Periférica/mortalidade , Valor Preditivo dos Testes , Período Pré-Operatório , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Extraction of a gallbladder through an endoscopic overtube during natural orifice translumenal endoscopic surgery (NOTES) transgastric cholecystectomy avoids potential injury to the esophagus. This study examined the rate of successful gallbladder specimen extraction through an overtube and hypothesized that preoperative ultrasound findings could predict successful specimen passage. METHODS: Gallbladder specimens from patients undergoing laparoscopic cholecystectomy were measured, and an attempt was made to pull the specimens through a commercially available overtube with an inner diameter of 16.7-mm. A radiologist blinded to the outcomes reviewed the available preoperative ultrasound measurements from these patients. Ultrasound dimensions including gallbladder length, width, and depth; wall thickness; common bile duct diameter; and size of the largest gallstone (LGS) were recorded. Multiple logistic regression analysis was performed to determine whether ultrasound findings and patient characteristics (age, body mass index [BMI], and sex) could predict the ability of a specimen to pass through the overtube. RESULTS: Of 57 patients, 44 (77%) who had preoperative ultrasounds available for electronic review were included in the final analysis. Gallstones were present in 35 (79%) of these 44 patients. Intraoperative gallbladder perforation occurred in 18 (41%) of the 44 patients, and 16 (36%) of the 44 gallbladders could be extracted through the overtube. Measurement of LGS was possible for 23 patients, and indeterminate gallstone size (IGS) was determined for 12 patients. The rate for passage of perforated versus intact gallbladders was similar (40% vs. 23%; p = 0.054). The LGS (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.02-1.33; p = 0.021) and IGS (OR, 22.97; 95% CI, 1.99-265.63; p = 0.025) predicted failed passage on multivariate logistic regression analysis. The passage rate was 80% for LGS smaller than 10 mm or no stones present, 18% for LGS 10 mm or larger, and 8% for IGS (p < 0.001). CONCLUSION: A majority of cholecystectomy specimens cannot pass through an endoscopic overtube. Preoperative ultrasound findings can predict successful specimen extraction. An IGS or a gallstone 10 mm or larger should be considered a relative contraindication to transgastric NOTES cholecystectomy.
Assuntos
Colecistectomia/instrumentação , Colelitíase/diagnóstico por imagem , Vesícula Biliar/diagnóstico por imagem , Cálculos Biliares/diagnóstico por imagem , Complicações Intraoperatórias/prevenção & controle , Cirurgia Endoscópica por Orifício Natural/instrumentação , Seleção de Pacientes , Antropometria/métodos , Índice de Massa Corporal , Colecistectomia/efeitos adversos , Colecistectomia/métodos , Colecistectomia Laparoscópica , Colecistite/diagnóstico por imagem , Colecistite/cirurgia , Colelitíase/cirurgia , Ducto Cístico/diagnóstico por imagem , Procedimentos Cirúrgicos Eletivos , Desenho de Equipamento , Esôfago/lesões , Estudos de Viabilidade , Feminino , Vesícula Biliar/lesões , Vesícula Biliar/patologia , Vesícula Biliar/cirurgia , Cálculos Biliares/patologia , Humanos , Técnicas In Vitro , Complicações Intraoperatórias/etiologia , Masculino , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/métodos , Tamanho do Órgão , Método Simples-Cego , Estômago , UltrassonografiaRESUMO
OBJECTIVES: To compare the effects of 3 different exercise training regimens on cardiorespiratory fitness and coronary risk factor reduction in subjects with unilateral stroke. DESIGN: A cluster assignment by residential location repeated-measures design. SETTING: University-based medical center. PARTICIPANTS: Fifty-five subjects with unilateral ischemic stroke were assigned to the following groups: intensity (n=18), duration (n=19), and therapeutic exercise (n=18). INTERVENTION: A 14-week intervention with subjects randomized to 1 of 3 interventions: (1) moderate intensity, shorter duration (MISD) exercise (gradually increasing exercise intensity while keeping exercise duration constant at 30 min), (2) low-intensity, longer duration (LILD) exercise (gradually increasing duration to 60 min while keeping exercise intensity constant), or (3) conventional therapeutic exercise (TE) consisting mainly of strength, balance, and range of motion activities. All groups exercised 3 days per week. MAIN OUTCOME MEASURES: Peak oxygen consumption (VO2peak), submaximal oxygen consumption (VO2), lipid panel, and resting blood pressure. RESULTS: The MISD group attained more favorable effects on systolic (P<.04) and diastolic blood pressure (P<.002) and total cholesterol (TC) (P<.036) compared with LILD and TE groups. Both MISD (P<.029) and LILD (P<.045) showed significant reductions in triglycerides compared with TE (P<.029). There was no significant change in VO2peak and submaximal VO2 in any of the groups. CONCLUSIONS: Overall, both MISD and LILD conditions achieved greater clinical and significant gains in coronary risk reduction compared with TE.
Assuntos
Terapia por Exercício/classificação , Terapia por Exercício/métodos , Aptidão Física , Reabilitação do Acidente Vascular Cerebral , Doença das Coronárias/etiologia , Doença das Coronárias/prevenção & controle , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/etiologia , Debilidade Muscular/reabilitação , Consumo de Oxigênio , Projetos Piloto , Comportamento de Redução do Risco , Acidente Vascular Cerebral/complicaçõesRESUMO
The umbrella cells that line the bladder are mechanosensitive, and bladder filling increases the apical surface area of these cells; however, the upstream signals that regulate this process are unknown. Increased pressure stimulated ATP release from the isolated uroepithelium of rabbit bladders, which was blocked by inhibitors of vesicular transport, connexin hemichannels, ABC protein family members, and nucleoside transporters. Pressure-induced increases in membrane capacitance (a measure of apical plasma membrane surface area where 1 microF approximately equals 1 cm2) were inhibited by the serosal, but not mucosal, addition of apyrase or the purinergic receptor antagonist PPADS. Upon addition of purinergic receptor agonists, increased capacitance was observed even in the absence of pressure. Moreover, knockout mice lacking expression of P2X2 and/or P2X3 receptors failed to show increases in apical surface area when exposed to hydrostatic pressure. Treatments that prevented release of Ca2+ from intracellular stores or activation of PKA blocked ATPgammaS-stimulated changes in capacitance. These results indicate that increased hydrostatic pressure stimulates release of ATP from the uroepithelium and that upon binding to P2X and possibly P2Y receptors on the umbrella cell, downstream Ca2+ and PKA second messenger cascades may act to stimulate membrane insertion at the apical pole of these cells.
Assuntos
Trifosfato de Adenosina/metabolismo , Membrana Celular/metabolismo , Receptores Purinérgicos P2/metabolismo , Bexiga Urinária/citologia , Urotélio , Trifosfato de Adenosina/agonistas , Animais , Apirase/metabolismo , Cálcio/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Capacitância Elétrica , Endocitose/fisiologia , Exocitose/fisiologia , Feminino , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Agonistas do Receptor Purinérgico P2 , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/metabolismo , Coelhos , Receptores Purinérgicos P2/genética , Receptores Purinérgicos P2X2 , Receptores Purinérgicos P2X3 , Transdução de Sinais/fisiologia , Urotélio/metabolismo , Urotélio/ultraestruturaRESUMO
Reversible cardiomyopathy has been reported in patients after liver transplantation. However, there are few data on the incidence, risk factors, and prognosis of this condition. Liver transplantation recipients who underwent preoperative right- and left-sided cardiac catheterization as well as preoperative transthoracic echocardiography from 2001 to 2005 were identified. Eighty-six patients met the outlined criteria and were included in the study. The incidence of severe heart failure (HF) after transplantation in this population was 6 of 86 (approximately 7%). Patients who developed HF were slightly older (mean age 61.2 +/- 8.9 vs 55.4 +/- 9.2 years, p = 0.08) but had similar preoperative ejection fractions (60 +/- 5% vs 57 +/- 8%, p = 0.22) and comparable systemic arterial blood pressure (116 +/- 22/62 +/- 11 vs 127 +/- 9/66 +/- 9, p >0.1). In addition, the severity of liver disease as measured by the model for end-stage liver disease score was not different between the 2 groups (23.9 +/- 9.7 vs 26 +/- 10.7, p = 0.5). There was also no significant difference in the preoperative cardiac index (3.8 +/- 1 vs 3.6 +/- 1.5 L/min/m2, p = 0.9) or pulmonary artery wedge pressure (13.6 +/- 5.8 vs 15.3 +/- 2.8 mm Hg, p = 0.42). The incidence of alcohol use as the presumed cause of liver failure was equivalent in the 2 groups (33% vs 25%, p = 0.65). The patients who developed HF did have significantly higher preoperative mean pulmonary arterial systolic pressures (43 +/- 10 vs 30 +/- 9 mm Hg, p = 0.02) and right ventricular systolic pressures (44 +/- 13 vs 34 +/- 8 mm Hg, p = 0.05). In conclusion, severe systolic HF may occur after liver transplantation in patients without traditional risk factors for HF. This study suggests that those patients with preoperative elevated right-sided cardiac pressures, as well as older patients, may be at excess risk for developing HF after transplantation.
Assuntos
Insuficiência Cardíaca/epidemiologia , Transplante de Fígado , Adulto , Idoso , Ecocardiografia Transesofagiana , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico por imagem , Humanos , Illinois/epidemiologia , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Can attending a communication skills workshop focused on advance care planning, shifting focus to palliative care, personal grief, managing anger, and culture and communication result in changes in attitudes and knowledge? One hundred and three clinicians completed surveys prior to and following the workshop resulting in significant changes in knowledge, attitudes and intent to change that persisted for at least 3 months. As most clinicians are not routinely exposed to learning communication skills for end-of-life conversations, opportunities to practice these skills in a safe supportive environment should be made available in medical schools, residency programs, and in the practice community.
Assuntos
Atitude Frente a Morte , Comunicação , Hábitos , Relações Médico-Paciente , Adaptação Psicológica , Atitude Frente a Saúde , Educação Médica , Humanos , Intenção , Competência Profissional , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To examine the antigenic distribution of human leukocyte antigens (HLA) of the human larynx. STUDY DESIGN AND SETTING: Twelve human larynges were examined for Class I (HLA-A, -B, -C) and Class II (HLA-DR) histocompatibility antigens using mouse monoclonal antibodies in an indirect immunoperoxidase assay. Structures of the larynx and surrounding tissues were examined and given a semiquantitative score based on HLA Class I and II expression. RESULTS: The mucosal surface epithelium of the larynx stains 2+ or stronger for HLA Class I antigens and 1+ for Class II antigens. The deeper submucosal glands stain 1+ for Class I antigens and 2+ or stronger for Class II antigens. Thyroid cartilage showed 2+ or stronger staining of the chondrocytes for Class I antigens only. Thyroid follicular cells also stain only for Class I antigens. Perichondrium and Schwann cells of nerves stain stronger for Class I antigens than Class II antigens. Cartilage matrix, muscle cells, and axons of nerves do not stain for either class of antigens. Endothelium stains 3+ for both classes of antigens. CONCLUSIONS: The detailed distribution of major transplantation antigens in the human larynx is elucidated. Class II antigens implicated as initiators of organ transplant rejection were primarily found in 6 areas: mucosal surface epithelium, submucosal glands, ducts, vascular endothelium, perichondrium, and Schwann cells of nerves. The relevance of these findings to the initiation and detection of laryngeal allograft graft rejection is discussed.
Assuntos
Antígenos HLA/metabolismo , Mucosa Laríngea/metabolismo , Endotélio Vascular/metabolismo , Rejeição de Enxerto/metabolismo , Antígenos HLA-A/metabolismo , Antígenos HLA-B/metabolismo , Antígenos HLA-C/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Imuno-Histoquímica , Laringe/transplante , Nervo Laríngeo Recorrente/metabolismo , Células de Schwann/metabolismoRESUMO
Worldwide, major depression is the leading cause of years lived with a disability, and the fourth cause of disability-adjusted life years. Depression is second only to hypertension as the most common chronic condition encountered in general medical practice. Unfortunately, despite the high prevalence of depression, under-recognition and under-treatment are common.Historically, clinicians have assessed the short-term effectiveness of antidepressants by response rates, often defined as a 50% reduction in depressive symptoms. However, this usually does not reflect true clinical remission, and residual symptoms are common. Persistence of residual symptoms appears to be a common link to relapse, chronic disability and suicide. The burden of not treating depression effectively to remission is significant, as the disease is an important contributor to the disability levels of the general population. Disability, in turn, has a profound impact on lost productivity and medical expenses. In 2000, depression cost the US more than US 83 billion dollars annually in lost productivity, medical expenses and premature death.Venlafaxine, a dual-acting serotonin norepinephrine (noradrenaline) reuptake inhibitor, may improve a patient's response to treatment and their chances of achieving complete remission compared with conventional antidepressant therapies, with the evidence for this being the strongest for comparisons with the selective serotonin receptor inhibitors (SSRIs). To date, there are only a small number of economic studies of venlafaxine, and most are cost or resource utilisation analyses with significant limitations. Nevertheless, two cost-effectiveness analyses of venlafaxine are available. They found venlafaxine had a lower average cost per patient achieving remission or per symptom-free day compared with SSRIs; one reported an incremental cost-effectiveness ratio for venlafaxine of US 586 dollars (year 2002 values) per additional patient achieving remission over 8 weeks, and the other found venlafaxine to be a dominant treatment choice over SSRIs over 6 months (year 2001 values). Although requiring further confirmation, these initial data suggest that venlafaxine is a cost-effective strategy for the treatment of depression. The availability of an effective armamentarium of antidepressant strategies, including venlafaxine, to achieve and sustain remission offers both clinical and economic value to all those touched by the burden of depression.
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Cicloexanóis/uso terapêutico , Depressão/tratamento farmacológico , Antidepressivos de Segunda Geração/economia , Antidepressivos de Segunda Geração/uso terapêutico , Efeitos Psicossociais da Doença , Cicloexanóis/economia , Depressão/economia , Humanos , Indução de Remissão , Prevenção Secundária , Cloridrato de VenlafaxinaRESUMO
The objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of pneumococcal conjugate vaccination for infants and children aged <5 years in Canada. A health state model incorporating incidence, vaccine efficacy, costs, and transitional probabilities for the health states (well, meningitis, bacteremia, otitis media, pneumonia, and death) was constructed for a 10-year time horizon. Implementation of a pneumococcal conjugate vaccine program in Canada for each annual birth cohort of 340,000 persons observed over 10 years would be expected to save approximately 12 lives and 100,000 cases of pneumococcal disease over 10 years, resulting in total savings of $67 million (Canadian dollars [Can$]). Vaccination of healthy infants would result in net savings for society if the vaccine costs less than Can$50 per dose. Moreover, for a vaccine purchase price of Can$67.50, infant vaccination would cost society Can$79,000 per life-year gained. Pneumococcal conjugate vaccination is a potentially cost-effective means of pneumococcal disease prevention.
Assuntos
Custos de Cuidados de Saúde , Vacinas Pneumocócicas/economia , Vacinas Conjugadas/economia , Canadá , Análise Custo-Benefício , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas/administração & dosagem , Medição de Risco , Vacinas Conjugadas/administração & dosagemRESUMO
BACKGROUND: The importance of incorporating quality-of-life (QoL) assessments into medical practice is growing as health care practice shifts from a "disease-based" to a "patient-centered" model. The prevalence of age-related macular degeneration (AMD) is increasing in today's aging population. The purpose of this paper is: (1) to discuss, by reviewing the current literature, the impact of AMD on patients' QoL and the utility of QoL assessments in evaluating the impact of AMD and its treatment; and (2) to make a recommendation for incorporating QoL into clinical practice. METHODS: We conducted a PubMed and an open Internet search to identify publications on the measurement of QoL in AMD, as well as the impact of AMD and the effect of treatment on QoL. A total of 28 articles were selected. RESULTS: AMD has been found to cause a severity-dependent decrement in QoL that is comparable to systemic diseases such as cancer, ischemic heart disease, and stroke. QoL impairment manifests as greater social dependence, difficulty with daily living, higher rates of clinical depression, increased risk of falls, premature admission to nursing homes, and suicide. The National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25) is the most widely used eye disease-specific QoL instrument in AMD. It has been shown to correlate significantly with visual acuity (VA). QoL reflects aspects of AMD including psychological well-being, functional capacity, and the ability to perform patients' valued activities, which are not captured by a single, numerical VA score. CONCLUSION: The literature shows that the adverse impact of AMD on QoL is comparable to serious systemic disease. Eye disease-specific instruments for measuring QoL, such as the NEI VFQ-25, have shown a significant correlation of QoL decrement with measures of disease severity, as well as significant QoL improvement with treatment. The NEI VFQ-25 and other validated instruments provide a wide-ranging assessment of vision-related functioning that is important to patients and complementary to VA measurement. We strongly recommend the incorporation of QoL assessment into routine clinical practice.
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BACKGROUND: The aim of this study was to investigate the link between atrial fibrillation (AF) and dyspepsia, as well as the contribution of dyspepsia to the overall burden of AF. METHODS: The 2008, 2009, and 2010 Japan National Health and Wellness Survey (NHWS) datasets were used in this study. The NHWS is an Internet-based survey administered to the adult population in Japan using a random stratified sampling framework to ensure demographic representativeness. The presence of dyspepsia was compared between those with and without AF. Among those with AF, the effect of dyspepsia on health status, work productivity, and activity impairment was examined, along with health care resource use using multivariable regression modeling and controlling for baseline differences. RESULTS: Among patients with AF (n = 565), the three most commonly reported comorbidities were hypertension (38.76%), dyspepsia (37.35%), and overactive bladder (28.72%). Patients with AF had 48.59% greater odds of reporting dyspepsia than those without AF (P < 0.05). Patients with dyspepsia used more AF medications (2.05 versus 1.54) and had been diagnosed more recently (9.97 versus 10.58 years). Dyspepsia was associated with significantly worse physical health status (P < 0.05) and significantly more absenteeism, overall work impairment, activity impairment, physician visits, and emergency room visits (all P < 0.05). CONCLUSION: Patients with AF in Japan experience a number of comorbidities, with dyspepsia being the most common noncardiovascular comorbidity. Given the prevalence and additional burden of this comorbidity across both humanistic and economic outcomes, the management of dyspepsia among patients with AF should be an area of greater focus.
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UNLABELLED: . OBJECTIVE: Menstrual symptoms are associated with various health problems in women and may also significantly impact their lives. This study aims to assess the current burden of menstrual symptoms in Japanese women. METHODS: Two online surveys were conducted among women aged 15-49 years, where sampling was designed to approximate the age and geographic distribution in Japan. The first survey collected data on menstrual symptom severity based on a modified, 35-item, Japanese version of the Menstrual Distress Questionnaire (mMDQ), current treatments, and impact on work productivity. The second survey collected costs of outpatient treatment within the previous 3 months. Additional outcomes of the second survey will be presented in a separate paper. RESULTS: In this study, 19,254 women had menses, with 74% suffering from menstrual symptoms. A total of 50% reported pain and 19% reported heavy bleeding. Increasing severity of menstrual symptoms and self-reported heavy bleeding were related to more outpatient visits and greater work productivity loss. Among subjects with heavy bleeding, increasing severity of symptoms was related to greater interference with daily life. The estimated annual economic burden extrapolated to the Japanese female population was 683 billion Japanese Yen (JPY) or ~8.6 billion United States Dollars (USD). LIMITATIONS: The study population may be biased due to the online survey method. CONCLUSIONS: To the authors' knowledge, this is the first large-scale research assessing outcomes by severity categories for all menstrual symptoms and women's perception of bleeding. A large proportion of women suffer from menstrual symptoms, and symptom severity impacts women's lives. Menstrual symptoms lead to significant economic burden, mainly due to work productivity loss. However, the majority of women do not visit a gynecologist, even when their menstrual symptoms are severe. Thus, increasing public awareness on the recently available medical treatments has the potential to improve the overall burden of menstrual problems.
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Distúrbios Menstruais/economia , Distúrbios Menstruais/epidemiologia , Absenteísmo , Adolescente , Adulto , Fatores Etários , Feminino , Gastos em Saúde/estatística & dados numéricos , Humanos , Japão , Menorragia/economia , Menorragia/epidemiologia , Pessoa de Meia-Idade , Visita a Consultório Médico , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Gravidade do Paciente , Prevalência , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: The goal of this study was to determine whether preoperative albumin level in vascular surgery patients is predictive of postoperative outcomes in the Veterans Affairs (VA) versus private sector and in open versus endovascular interventions. METHODS: A retrospective analysis of male patients with peripheral arterial disease, carotid artery disease, and abdominal aortic aneurysms who underwent open or endovascular interventions at the Jesse Brown VA Medical Center or Northwestern Memorial Hospital from January 2006 to June 2009 was conducted. Preoperative demographics and postoperative outcomes were assessed. Major adverse events (MAE) were defined as myocardial infarction, stroke, or death. RESULTS: A total of 591 men were included. Preoperative albumin level was significantly higher in VA versus private sector patients (3.6 ± .5 g/dL vs 3.2 ± .8 g/dL, respectively; P = .0001) and endovascular versus open patients (3.6 ± .6 g/dL vs 3.3 ± .7 g/dL, respectively; P < .0001). Albumin level was an independent predictor of MAE (odds ratio [OR], .46; P = .04) and 1-year death (OR, .35; P = .01) for all patients, and was predictive of MAE (OR, .40; P = .05) and 1-year death (OR, .23; P = .0008) in the open cohort. CONCLUSIONS: Preoperative malnutrition has important prognostic implications for vascular surgery patients in both the VA and private hospital settings, especially for those patients undergoing open repair.
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Aneurisma da Aorta Abdominal/cirurgia , Doenças das Artérias Carótidas/cirurgia , Hospitais de Veteranos , Desnutrição/complicações , Doença Arterial Periférica/cirurgia , Albumina Sérica/metabolismo , Procedimentos Cirúrgicos Vasculares , Idoso , Aneurisma da Aorta Abdominal/sangue , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/mortalidade , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/mortalidade , Chicago , Estudos de Coortes , Procedimentos Endovasculares , Hospitais Privados , Humanos , Modelos Logísticos , Masculino , Desnutrição/sangue , Desnutrição/diagnóstico , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/mortalidade , Doença Arterial Periférica/sangue , Doença Arterial Periférica/complicações , Doença Arterial Periférica/mortalidade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Período Pré-Operatório , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Resultado do Tratamento , Saúde dos VeteranosRESUMO
BACKGROUND: Newborn alertness soon after birth facilitates mother-infant interaction and may be related to umbilical cortisol levels. Yet, little is known about whether epidural analgesia influences umbilical cortisol at birth. AIM: The aims of this study were to explore relationships between exposure to epidural analgesia and maternal and umbilical cortisol; maternal and umbilical cortisol levels at birth; and umbilical cortisol and infant alertness after birth. METHOD: Forty women were self-selected to unmedicated or epidural labors in this pilot study. Maternal saliva and infant umbilical artery (UA) plasma at birth were enzyme immunoassayed for cortisol. Infant alertness was assessed nearly 1 hr after birth. RESULTS: Maternal cortisol was higher in the unmedicated versus epidural group (p = .003). Umbilical cortisol was not related to epidural analgesia exposure but was related to duration of labor (higher cortisol with longer labors; p = .026). Maternal cortisol level explained 55% of the variance in umbilical cortisol in the unmedicated group (p = .002), but there was no significant shared variance in the epidural sample (p = .776). There was a positive correlation (r(2) = .17, p = .008) between umbilical cortisol and infant alertness. Latina infants demonstrated a higher frequency of alertness than Black infants. In multivariate analysis, umbilical cortisol (p = .049) and race/ethnicity (p = .024) remained significant predictors of infant alertness. CONCLUSIONS: Our findings indicate that higher umbilical cortisol is related to greater infant alertness soon after birth. While epidural analgesia did not directly relate to infant cortisol, other factors contributed to higher umbilical cortisol.