Predictors Of Poor Long-term Outcome Research Articles

Vagus nerve stimulation in experimental heart failure

Chronic heart failure (HF) is associated with autonomic dysregulation characterized by a sustained increase in sympathetic drive and by withdrawal of parasympathetic activity. Sympathetic overdrive and increased heart rate are predictors of poor long-term outcome in patients with HF. Considerable evidence exists that supports the use of pharmacologic agents that partially inhibit sympathetic activity as effective long-term therapy for patients with HF; the classic example is the wide use of selective and non-selective beta-adrenergic receptor blockers. In contrast, modulation of parasympathetic activation as potential therapy for HF has received only limited attention over the years given its complex cardiovascular effects. In this article, we review the results of recent experimental animal studies that provide support for the possible use of electrical Vagus nerve stimulation (VNS) as a long-term therapy for the treatment of chronic HF. In addition to exploring the effects of chronic VNS on left ventricular (LV) function, the review will also address the effects of VNS on potential modifiers of the HF state that include cytokine production and nitric oxide elaboration. Finally, we will briefly review other nerve stimulation approaches which is also currently under investigation as potential therapeutic modalities for treating chronic HF.

Is an involved circumferential resection margin following oesphagectomy for cancer an important prognostic indicator?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether an involved circumferential resection margin (CRM) following oesophagectomy for cancer is an independent predictor of poor long-term survival. Six hundred and fourteen papers were found using the reported search, of which seven represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group, study type, relevant outcomes and results of these papers are tabulated. Of these studies, four were conducted on patients who predominantly did not receive preoperative chemotherapy and showed conflicting results as to the prognostic significance of CRM involvement. However, three later studies conducted on patients who predominantly did receive preoperative chemotherapy showed that CRM involvement to be an independent predictor of long-term survival. We conclude that for patients who undergo oesophagectomy alone as a treatment for oesophageal cancer, the prognostic importance of CRM involvement is unclear. However, for patients who undergo preoperative chemotherapy prior to surgery, there does appear to be emerging evidence supporting the concept that CRM involvement is an independent predictor of poor long-term outcome.

Effects of chronic renal insufficiency and anemia upon long-term outcomes in patients undergoing percutaneous coronary intervention

To assess whether chronic renal insufficiency and anemia are significant independent and combined predictors of poor long-term outcomes after percutaneous coronary intervention (PCI). We examined the clinical and outcome data of 3770 PCI patients based on the pre-PCI values of glomerular filtration rate (GFR) and hemoglobin (Hb). Depending on their baseline GFR and Hb, the patients were classified into six groups: normal renal function with anemia or not; mild renal impairment with combined anemia or not; severe renal insufficiency with anemia or not. The clinical features and prognosis of patients were compared. Significant differences were found between the groups regarding female gender, age, body mass index, prior history of hypertension, diabetes mellitus, prior stroke, acute coronary syndrome, systolic blood pressure, left ventricular ejection fraction, total serum cholesterol, LDL-C and angiographic features (P < 0. 01). When evaluated as continuous variables, GFR and Hb were independent predictors of long-term mortality after adjusting for effects of each other (GFR: HR 0.979, 95% CI 0.960-0.999, P = 0.035; Hemoglobin: HR 0.952, 95% CI 0.921-0.984, P = 0.004). Mild renal insufficiency with anemia (HR 4.123, 95% CI 1.637-10.386, P = 0.003), severe renal insufficiency without anemia (HR 5.287, 95% CI 1.627-17.183, P = 0. 006) and severe renal insufficiency with anemia (HR 7.134, 95% CI 2.180-23.342, P = 0.001) having a statistically significant decrease in survival in patients undergoing PCI . Renal insufficiency and anemia are significant independent and combined predictors of long-term mortality in patients undergoing PCI.

Mindfulness Meditation and Cognitive Behavioral Therapy for Insomnia: A Naturalistic 12-Month Follow-up

A unique intervention combining mindfulness meditation with cognitive behavioral therapy for insomnia (CBT-I) has been shown to have acute benefits at posttreatment in an open label study. The aim of the present study was to examine the long-term effects of this integrated intervention on measures of sleep and sleep-related distress in an attempt to characterize the natural course of insomnia following this treatment and to identify predictors of poor long-term outcome. Analyses were conducted on 21 participants, who provided follow-up data at six and 12 months posttreatment. At each time point, participants completed one week of sleep and meditation diaries and questionnaires related to mindfulness, sleep, and sleep-related distress, including the Pre-Sleep Arousal Scale, the Glasgow Sleep Effort Scale, the Kentucky Inventory of Mindfulness Skills, and the Insomnia Episode Questionnaire. Analyses examining the pattern of change across time (baseline, end of treatment, six months, and 12 months) revealed that several sleep-related benefits were maintained during the 12-month follow-up period. Participants who reported at least one insomnia episode (>or=1 month) during the follow-up period had higher scores on the Pre-Sleep Arousal Scale (P < .05) and the Glasgow Sleep Effort Scale (P < .05) at end of treatment compared with those with no insomnia episodes. Correlations between mindfulness skills and insomnia symptoms revealed significant negative correlations (P < .05) between mindfulness skills and daytime sleepiness at each of the three time points but not with nocturnal symptoms of insomnia. These results suggest that most sleep-related benefits of an intervention combining CBT-I and mindfulness meditation were maintained during the 12-month follow-up period, with indications that higher presleep arousal and sleep effort at end of treatment constitute a risk for occurrence of insomnia during the 12 months following treatment.

Hyperdense Basilar Artery Sign on Unenhanced CT Predicts Thrombus and Outcome in Acute Posterior Circulation Stroke

In acute stroke patients, the presence of a hyperdense middle cerebral artery sign on unenhanced CT is a specific but insensitive indicator of acute thrombosis. Our purpose was to determine whether the hyperdense basilar artery (HDBA) sign has utility in detecting thrombosis and predicting outcome in patients presenting with signs and symptoms of posterior circulation stroke. Unenhanced CT scans obtained within 24 hours of symptom onset in 95 patients with suspected posterior circulation stroke were reviewed. Three neuroimagers blinded to clinical outcome and results of the concurrent CT angiography (which served as the reference standard) rated presence of HDBA sign on a 5-point scale for level of certainty (1=definitely absent; 5=definitely present). Receiver operating characteristic curve analysis was performed. Short-term outcome was measured by discharge National Institute of Health Stroke Scale (NIHSS) scores; long-term outcome was measured by 6-month modified Rankin score (dichotomized, poor outcome defined as modified Rankin score >2). The following variables were correlated with short-term and long-term outcome by univariate analysis: HDBA sign, age, sex, time from stroke onset to imaging, admission NIHSS, history of stroke/TIA, atrial fibrillation, coronary artery disease, hypertension, diabetes, hypercholesterolemia, tobacco use, and thrombolysis. Variables showing correlation with P<0.1 were included in multiple regression analysis. Using a level of certainty cutoff score of >/=4 (probable, definite), HDBA sign had 71% sensitivity, 98% specificity, 94% accuracy, 83% positive predictive value, and 95% negative predictive value for basilar artery occlusion. In univariate analysis, factors significantly correlated with discharge NIHSS were: admission NIHSS (P<0.0001; r=0.77), HDBA sign (P=0.01), and diabetes (P=0.02). Factors showing significant correlation or association with poor long-term outcome were age (P=0.02), admission NIHSS (P=0.007), HDBA sign (P=0.02), and history of stroke or TIA (P=0.007). The odds ratio of HDBA sign for predicting poor long-term outcome was 5.3 (95% CI, 1.1-33.3). In multiple regression analysis, the only independent predictors of discharge NIHSS were admission NIHSS (P<0.0001) and HDBA sign (P=0.004). Significant independent predictors of poor long-term outcome were age (P=0.02), admission NIHSS (P=0.008), history of stroke/TIA (P=0.03), and HDBA sign (P=0.05). In patients presenting with a high pretest probability of posterior circulation stroke based on clinical symptoms, the presence of the HDBA sign on unenhanced CT is a strong predictor of basilar artery thrombosis, and both short- and long-term outcome.

Bleeding and outcome in acute coronary syndrome: Insights from continuous electrocardiogram monitoring in the Integrilin and Enoxaparin Randomized Assessment of Acute Coronary Syndrome Treatment (INTERACT) trial

Bleeding is associated with adverse outcome in acute coronary syndromes. However, the precise pathophysiologic mechanisms have not been elucidated. We sought to determine the relationship between bleeding and myocardial ischemia detected by concurrent continuous electrocardiogram (ECG) monitoring and their independent long-term prognostic significance. The INTERACT trial was a randomized controlled trial of enoxaparin versus unfractionated heparin in patients with high-risk non-ST-elevation acute coronary syndromes. Continuous ECG monitoring, performed after enrollment up to 96 hours, was analyzed by an automated algorithm and reviewed by a blinded cardiologist. We centrally adjudicated all bleeding and clinical events in a blinded fashion and calculated the Global Registry of Acute Coronary Events risk score (a validated predictor of mortality) for each patient. Of the 746 patients enrolled, 34 (4.6%) developed major bleeding within 96 hours. After a median follow-up of 2.4 years, patients with bleeding had a higher risk of death (28.4% vs 7.3%, P < .001) and death/myocardial infarction (38.0% vs 12.9%, P < .001) compared with those without bleeding. Overall, 619 patients survived the first 96 hours with complete data on continuous ECG monitoring. Bleeding was associated with the simultaneous presence of ST-segment shifts on continuous ECG monitoring (P = .03). After adjusting for Global Registry of Acute Coronary Events risk score and myocardial ischemia detected by continuous ECG monitoring, major bleeding remained an independent predictor of death (adjusted hazard ratio = 3.48, 95% confidence interval 1.51-8.03, P = .003) and death/myocardial infarction (adjusted hazard ratio = 2.85, 95% confidence interval 1.40-5.78, P = .004). Bleeding is a powerful independent predictor of poor long-term outcome, even after adjusting for other associated prognostic factors such as advanced age and renal dysfunction. Although bleeding is associated with concurrent myocardial ischemia, its adverse prognostic impact may be mediated by complex pathophysiologic mechanisms rather than myocardial ischemia alone. Our findings suggest that future investigations should focus on other biologically plausible mechanisms.

Metabolic syndrome and resistance to IV thrombolysis in middle cerebral artery ischemic stroke

The metabolic syndrome (MetS) is a cluster of vascular risk factors associated with a prothrombotic state. We aimed to evaluate the impact of MetS on the response to systemic tPA treatment in patients with acute middle cerebral artery (MCA) ischemic stroke. We studied 100 consecutive patients with ischemic stroke with MCA occlusions on prebolus transcranial Doppler (TCD) examination treated with tPA following SITS-MOST criteria. MetS was diagnosed following AHA/NHLBI-2005 criteria. Resistance to thrombolysis was defined as the absence of TCD-assessed complete MCA recanalization 24 hours after tPA infusion. Infarct volume was measured on CT scans. Long-term clinical outcome was evaluated by the modified Rankin scale (mRS) score at day 90. Fifty-eight (58%) patients fulfilled MetS criteria. Median prebolus NIH Stroke Scale score was 17. Forty (42%) patients showed resistance to clot dissolution, and 53 (53%) had poor clinical outcomes (mRS > 2). A multivariable-adjusted logistic regression model identified MetS as independently associated with resistance to thrombolysis (OR 4.7, 95% CI [1.7-13.6], p = 0.004). In the whole sample, MetS was associated with mRS > 2 (OR 2.4 [1.1-5.4], p = 0.03), although this association was no longer significant after multivariable adjustment. However, in patients with atherothrombotic stroke, MetS emerged as an independent predictor of poor long-term outcome (adjusted OR 13.9 [1.3-148.7], p = 0.02). In our series, the metabolic syndrome was associated with a poor response to thrombolysis in patients with acute middle cerebral artery occlusions, as reflected by a higher resistance to clot dissolution.

Results of Coronary Bypass and Valve Operations for Mitral Valve Regurgitation

Combined coronary bypass grafting and valve procedures for mitral valve regurgitation result in poor outcomes, but the impact of the etiology of valve regurgitation on operative and long-term outcomes is not well defined. A retrospective analysis of 468 patients who had combined coronary bypass grafting and valve operations for mitral regurgitation showed that 78% had valve repairs and 22% had replacements for ischemic (45%) or degenerative (55%) disease. Predictors of operative mortality were ischemic mitral regurgitation, failure to use the internal mammary artery for grafting, severe coronary disease, acute myocardial infarction, low ejection fraction, advanced heart failure, emergency operation, and mitral valve replacement. The 5-year survival rates for propensity-matched patients with ischemic or degenerative disease were similar (66%). Low ejection fraction (< 35%), advanced age (> 67 years), valve replacement surgery, residual mitral regurgitation, and severe coronary artery disease were predictors of poor long-term outcome. Although the operative outcomes of ischemic mitral regurgitation were poor compared to those of degenerative disease, the long-term survival was similar in both groups of propensity-matched patients. Left ventricular remodeling, an optimal valve procedure without residual mitral regurgitation, and left ventricular function are more important determinants of long-term outcome than the etiology of valve regurgitation.

Patient outcomes in schizophrenia II: the impact of cognition

Background. – Cognitive dysfunction is increasingly considered to be the strongest clinical predictor of poor long-term outcome in schizophrenia. Associations have been found between the severity of cognitive deficits and social dysfunction, impairments in independent living, occupational limitations, and disturbances in quality of life (QOL). Methods. – In this cross-sectional study, the relationships of cognitive deficits and treatment outcomes in terms of QOL, needs, and psychosocial functioning were examined in 60 outpatients with schizophrenia who had a duration of illness over 2 years and had been treated with either clozapine or olanzapine for at least 6 months. Results. – The present study suggests that cognitive functioning might be a predictor of work functioning/independent living outcome in stabilized patients with schizophrenia: deficits of visual memory and working memory were negatively associated with occupational functioning, and older patients lived independently and/or in a stable partnership more often. The patients' assessments of QOL and needs for care did not show any significant associations with cognitive functioning. Discussion. – These findings suggest that cognitive functioning is a key determinant of work functioning/independent living for stable outpatients with schizophrenia.

Why do kidney grafts fail?A long-term single-center experience.

Chronic allograft failure remains the main problem limiting long-term success after kidney transplantation. The aim of this retrospective analysis was to define clinical and histological parameters associated with favorable or poor 10-year outcome. To compare outcome we defined two groups of cadaveric-allograft recipients: a good-outcome group (GOG), composed of 145 cadaveric-kidney recipients who had lived with a functioning graft for at least 10 years and who were either still alive or had died with the functioning graft, and a poor-outcome group (POG) consisting of 86 cadaveric-kidney recipients who had had a functioning graft for at least 1 year and had returned to dialysis between 1 and 10 years after transplantation. The following factors were found to be statistically significant indicators of poor outcome: advanced donor age ( P=0.0001); a first biopsy-proven acute rejection episode within the 1st year ( P<0.0001); more than one acute rejection episode within the 1st year ( P<0.0001); acute vascular rejection, especially if occurring after the 3rd month ( P<0.0001); chronic sclerosing rejection ( P<0.0001); glomerulonephritis in the graft ( P=0.0001); and non-compliance and suboptimal medical treatment (15% of the POG). The mean plasma creatinine and mean urine protein-to-creatinine ratios were significantly lower at 1 month and 1 year in the GOG. In conclusion, advanced donor age, acute rejection episodes with vascular involvement, chronic sclerosing rejection, non-compliance, and suboptimal medical treatment are strong predictors of a poor long-term outcome. The plasma creatinine and protein-to-creatinine ratios at 1 year are the best predictors of good or poor long-term outcome.

Long-term disability after first-ever stroke and related prognostic factors in the Perth Community Stroke Study, 1989-1990.

Few reliable estimates of the long-term functional outcome after stroke are available. This population-based study aimed to describe disability, dependency, and related independent prognostic factors at 5 years after a first-ever stroke in patients in Perth, Western Australia. All individuals with a suspected acute stroke who were resident in a geographically defined region (population, 138 708) of Perth, Western Australia, were registered prospectively and assessed according to standardized diagnostic criteria over a period of 18 months in 1989 to 1990. Patients were followed up prospectively at 4 and 12 months and 5 years after the index event. There were 370 cases of first-ever stroke, and 277 patients survived to 30 days. Of these early survivors, 152 (55%) were alive at 5 years, and among those who were neither institutionalized (n=146) nor disabled (n=129) at the time of their stroke, 21 (14%) were institutionalized in a nursing home, and 47 (36%) were disabled. The most important predictors of death or disability at 5 years were increasing age, baseline disability defined by a Barthel Index score of <20/20 (odds ratio [OR], 6.3; 95% confidence interval [CI], 2.7 to 14), moderate hemiparesis (OR, 2.7; 95% CI, 1.1 to 6.2), severe hemiparesis (OR, 4.5; 95% CI, 1.1 to 19), and recurrent stroke (OR, 9.4; 95% CI, 3.0 to 30). A low level of activity before the stroke was a significant predictor of institutionalization, and subsequent recurrent stroke was a consistent, independent predictor of institutionalization, disability, and death or institutionalization, increasing the odds of each of these 3 adverse outcomes by 5- to 15-fold. Among 30-day survivors of first-ever stroke, about half survive 5 years; of survivors, one third remain disabled, and 1 in 7 are in permanent institutional care. The major modifiable predictors of poor long-term outcome are a low level of activity before the stroke and subsequent recurrent stroke. Efforts to increase physical activity among the elderly and to prevent recurrent stroke in survivors of a first stroke are likely to reduce the long-term burden of cerebrovascular disease.

Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke.

To evaluate the prognostic impact of early pathologic sympathetic activation after stroke. The authors examined 112 consecutive patients (mean age, 69 years; 60 men) with their first brain infarction. A pathologic sympathetic activation was presumed if the initial norepinephrine level exceeds 300 pg/mL. In addition, involvement of the insular cortex, nighttime blood pressure changes, and several cardiovascular risk factors were determined. One-year outcome measures were mortality rate, cardiovascular and cerebrovascular events, and activities of daily living (Barthel index and Rankin score). Norepinephrine levels greater than 300 pg/mL, nighttime blood pressure increases, and insular involvement were associated with a lower Barthel index (p < 0.005) at the 1-year follow-up. By stepwise logistic regression analysis, insular infarction, serum norepinephrine concentration, right-sided infarction, and nighttime blood pressure increase were significant and independent predictors of an unfavorable functional outcome. Cox regression analysis showed a higher rate of cardiovascular and cerebrovascular events (hazard ratio, 2.9; 95% CI, 1.07; 6.83; p < 0.04) in patients with initially increased norepinephrine concentrations. The involvement of the insular cortex, the occurrence of a pathologic nighttime blood pressure increase, and an initially increased serum norepinephrine concentration are independent predictors of poor long-term outcome.

Delirium on hospital admission in aged hip fracture patients: prediction of mortality and 2-year functional outcomes.

Hip fracture patients are at increased risk of confusion or delirium due to the trauma associated with the injury and the rapid progression to hospitalization and surgery, in addition to the pain and loss of function experienced. Hip fracture patients who develop delirium may require longer hospital stays, are more often discharged to long-term care, and have a generally poor prognosis for returning home or regaining function in activities of daily living (ADL). The present study examines the impact of delirium present on hospital admission in a sample of 682 non-demented, aged hip fracture patients residing in the community at the time of their fracture. In-hospital assessments designed to assess both prefracture and postfracture functioning, as well as follow-up interviews at 2, 6, 12, 18, and 24 months postfracture, were obtained from participants. Analyses indicate that baseline or admission delirium is an important prognostic predictor of poor long-term outcomes in persons without known cognitive impairment, after controlling for age, gender, race, comorbidity, and functional status. Delirium at admission (i.e., prior to surgery) was associated with poorer functioning in physical, cognitive, and affective domains at 6 months postfracture and slower rates of recovery. Impairment and delays in recovery may be further exacerbated by increased depressive symptoms in confused patients over time. Delirium on hospital admission was not a significant predictor of mortality after adjustment for confounding factors. The present findings further emphasize the significance of immediate detection and treatment of delirium in hip fracture patients to ameliorate the short and long-term effects of acute confusion on functional outcomes.

Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.

There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease. Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%. The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases <12 months (p = 0.03), number of hepatic tumors >1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor. Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.

Family history as a predictor of poor long-term outcome in depression.

We investigated whether family history had prognostic significance in depression in a study which addressed some of the methodological shortcomings of previous studies. We collected family history data on a consecutive series of 89 patients admitted with RDC major depression, blind to the outcome of the proband. This comprised 116, 283 and 120 first-degree relatives examined with the SADS-L, FH-RDC and case note data, respectively. The outcome of 74 of these probands (83%), previously categorised into four operationally defined groups, was then examined. A positive family history of severe psychiatric illness (i.e. a relative with a history of either a psychosis, hospitalised depression or suicide) was associated with poor outcome in the proband. This association persisted after controlling for variable family size, age structure and gender. As family history was correlated with neither Kendell's neurotic/psychotic index nor the proband's neuroticism score, an individual with high scores an all three would have a greatly increased chance of having a poor outcome. A family history of severe psychiatric illness in a first-degree relative may be useful as one of the vulnerability factors for predicting poor long-term outcome in depression.

Long Term Outcome of Anorexia Nervosa

The long-term outcome (mean follow-up period 5.7 years) for 20 patients with anorexia nervosa was assessed on a comprehensive battery of self-report inventories and a structured clinical interview. Two thirds of the cohort were improved to a clinically significant degree at follow-up, but the majority still showed higher than normal scores on inventories of anorexic symptomatology, social maladjustment, anxiety, and hostility. The remaining one third were unimproved and demonstrated a broad range of impairment including distorted attitudes toward eating, overconcern about body shape, poor social functioning, high levels of anxiety, hostility, depression, and external locus of control. Moderate to strong correlations were found across outcome measures. Longer duration of eating difficulties before presentation was a strong predictor of poor long-term outcome, suggesting a chronic relapsing form of the disorder occurred in a subgroup of patients.

HM-PAO-SPECT in persistent vegetative state after head injury: Prognostic indicator of the likelihood of recovery?

Management of patients presenting with traumatic persistent vegetative state (PVS) calls for extensive resources. The ability to predict whether or not a patient is likely to recover is a critical issue. In 12 patients with PVS admitted consecutively for early rehabilitation after head injury, pattern of brain activity was measured by 99mTc-hexamethyl-propylenamineoxime (99mTc-HM-PAO) brain SPECT (single photon emission computer tomography). All patients were re-investigated after a mean observation period of 3 years. A global reduction of cortical blood flow was a reliable predictor of poor long-term outcome, but the demonstration of only focal deficits did not reliably indicate a favourable outcome. Brain SPECT may help to improve outcome prediction in patients with traumatic PVS.