N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.

BACKGROUND: N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results. METHODS: The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds. RESULTS: The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds. CONCLUSIONS: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis.

OBJECTIVES: The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND: Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS: We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS: Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS: Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

Is Emergency Department length of stay associated with inpatient mortality?

AIMS: To determine whether Emergency Department length of stay (EDLOS) greater than 8 hours (EDLOS > 8 hours) and less than 4 hours (EDLOS < 4 hours) were independently associated with inpatient mortality taking into account patient comorbidities and age; and to determine the impact of EDLOS on inpatient length of stay (IPLOS). METHODS: This was a retrospective data analysis of emergency presentations and inpatient admissions during 2007 at The Northern Hospital, Victoria. RESULTS: Taking into account age and disease states, EDLOS > 8 hours was not associated with inpatient mortality (odds ratio 1.1; 95% confidence interval (CI) 0.9-1.4, P = 0.4), nor was EDLOS < 4 hours (odds ratio 0.9; 95% CI 0.6-1.4, P = 0.6) associated with reduced mortality. EDLOS > 8 hours was significantly associated with longer inpatient length of stay (IPLOS) (P < 0.001) adjusting for medical comorbidities. Mean EDLOS and IPLOS were significantly longer for patients over 75 years of age. CONCLUSION: EDLOS > 8 hours and EDLOS < 4 hours are not independently associated with mortality. A longer EDLOS is independently associated with longer IPLOS.

Postoperative B-type natriuretic peptide for prediction of major cardiac events in patients undergoing noncardiac surgery: systematic review and individual patient meta-analysis.

BACKGROUND: It is unclear whether postoperative B-type natriuretic peptides (i.e., BNP and N-terminal proBNP) can predict cardiovascular complications in noncardiac surgery. METHODS: The authors undertook a systematic review and individual patient data meta-analysis to determine whether postoperative BNPs predict postoperative cardiovascular complications at 30 and 180 days or more. RESULTS: The authors identified 18 eligible studies (n = 2,051). For the primary outcome of 30-day mortality or nonfatal myocardial infarction, BNP of 245 pg/ml had an area under the curve of 0.71 (95% CI, 0.64-0.78), and N-terminal proBNP of 718 pg/ml had an area under the curve of 0.80 (95% CI, 0.77-0.84). These thresholds independently predicted 30-day mortality or nonfatal myocardial infarction (adjusted odds ratio [AOR] 4.5; 95% CI, 2.74-7.4; P < 0.001), mortality (AOR, 4.2; 95% CI, 2.29-7.69; P < 0.001), cardiac mortality (AOR, 9.4; 95% CI, 0.32-254.34; P < 0.001), and cardiac failure (AOR, 18.5; 95% CI, 4.55-75.29; P < 0.001). For greater than or equal to 180-day outcomes, natriuretic peptides independently predicted mortality or nonfatal myocardial infarction (AOR, 3.3; 95% CI, 2.58-4.3; P < 0.001), mortality (AOR, 2.2; 95% CI, 1.67-86; P < 0.001), cardiac mortality (AOR, 2.1; 95% CI, 0.05-1,385.17; P < 0.001), and cardiac failure (AOR, 3.5; 95% CI, 1.0-9.34; P = 0.022). Patients with BNP values of 0-250, greater than 250-400, and greater than 400 pg/ml suffered the primary outcome at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with N-terminal proBNP values of 0-300, greater than 300-900, and greater than 900 pg/ml suffered the primary outcome at a rate of 1.8, 8.7, and 27%, respectively. CONCLUSIONS: Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery.

Electrocardiograph changes, troponin levels and cardiac complications after orthopaedic surgery.

INTRODUCTION: The relationship between electrocardiograph (ECG) changes and troponin levels after the emergency orthopaedic surgery are not well characterised. The aim of this study was to determine the correlation between ECG changes (ischaemia or arrhythmia), troponin elevations perioperatively and cardiac complications. MATERIALS AND METHODS: One hundred and eighty-seven orthopaedic patients over 60 years of age were prospectively tested for troponin I and ECGs were performed on the fi rst 3 postoperative mornings or until discharge. RESULTS: The incidences of pre- and postoperative troponin elevation were 15.5% and 37.4% respectively, the majority were asymptomatically detected. Most of the patients who sustained a troponin rise did not have any concomitant ECG changes (51/70 or 72.9%). Postoperative ECG changes were noted in 18.4% (34/185) and of those with ECG changes, slightly more than half (55.9%) had a troponin elevation. Most ECG changes occurred on postoperative day 1 and were non-ST elevation in type. ECG changes occurred more frequently with higher troponin levels. Postoperative troponin elevation (P = 0.018) and not preoperative troponin level (P = 0.060) was associated with ECG changes on univariate analysis. Two premorbid factors were predictors of postoperative ECG changes using multivariate logistical regression; age [odds ratio (OR), 1.05; 95% CI, 1.005 to 1.100, P = 0.029) and sex OR, 2.4; 95% CI, 1.069 to 5.446, P = 0.034). Twenty patients sustained postoperative cardiac complications; 9 (45%) were associated with ECG changes and 16 (80%) with postoperative troponin elevation. Pre- or postoperative troponin elevation better predicted cardiac complications compared with preoperative ECG changes. CONCLUSION: Electrocardiograph changes do not necessarily accompany troponin elevations after the emergency orthopaedic surgery but are more likely to have higher troponin levels. The best predictor of postoperative cardiac complications is troponin elevation.

Hospital treatment in residential care facilities is a viable alternative to hospital admission for selected patients.

AIM: To determine if hospital treatment in residential care facilities, led by a geriatric team, might be a viable alternative to inpatient admission for selected patients. METHODS: Case series with a new intervention were compared with historical controls receiving the conventional treatment. Treatment in residential care facilities (TRC) by the Residential Care Intervention Program in The Elderly (RECIPE) service was compared against the conventional treatment group, aged care unit (ACU) inpatients. RESULTS: A total of 95 patients in TRC and 167 patients in ACU were included. The mean Charlson Comorbidity Index score was 7 in both groups and demographics were similar, except more patients in the TRC group had dementia. Palliative care support was provided to 35.8% in the TRC group, compared with 7.8% in ACU, P < 0.001. Six-month mortality rates were similar at 30% for both groups. Rehospitalization rates at 6 months were similar at 41% for both groups. Length of care was significantly shorter for TRC (mean 2 days) compared with ACU (mean 11 days), P < 0.001. CONCLUSIONS: Hospital treatment in residential care is viable for most patients, including those with dementia and those who need palliative care support. This model of care offers a valuable geriatric service to residents who would prefer to avoid hospital transfers, with no difference in mortality or rehospitalization rates for those treated in residential care, but a significant reduction in length of care.

Does cardiology intervention improve mortality for post-operative troponin elevations after emergency orthopaedic-geriatric surgery? A randomised controlled study.

OBJECTIVES: Troponin elevations are common after emergency orthopaedic surgery and confer a higher mortality at one year. The objective was to determine if comprehensive cardiology care after emergency orthopaedic surgery reduces mortality at one year in patients who sustain a post-operative troponin elevation versus standard care. METHODS: A randomised controlled trial was conducted at a metropolitan teaching hospital in Melbourne, Australia. 187 consecutive patients were eligible with 70 patients randomised. Troponin I was tested peri-operatively and patients with a troponin elevation were randomised to cardiology care versus standard ward management. The main outcome measure was one year mortality. RESULTS: The incidence of a post-operative troponin elevation was 37.4% (70/187) and these 70 patients were randomised. In-hospital cardiac complications were similar between the randomised groups: standard care (7/35 or 20.0%) versus cardiology care (8/35 or 22.9%). There was no difference in 1 year mortality between the randomised groups (6/35 or 17.1% in each group). Multivariate predictors of 1 year mortality were post-operative troponin elevation OR 4.3 (95% CI, 1.1-16.4, p=0.035), age OR 1.1 (95% CI, 1.02-1.2, p=0.016) and number of comorbidities OR 2.1 (95% CI, 1.3-3.5, p=0.004). At 1 year 35/187 (18.7%) sustained a cardiac complication and 23/35 (65.7%) had a troponin elevation. CONCLUSIONS: There was no difference in mortality between patients with a post-operative troponin elevation randomised to cardiology care compared with standard care. Troponin elevation predicted one year mortality. Further research is needed to find an effective intervention to reduce mortality.

N-terminal pro-brain natriuretic peptide and angiotensin-converting enzyme-2 levels and their association with postoperative cardiac complications after emergency orthopedic surgery.

The prognostic usefulness of the cardiac biomarkers N-terminal pro-brain natriuretic peptide (NT-proBNP) and angiotensin-converting enzyme 2 (ACE-2), in predicting adverse cardiac outcomes after orthopedic surgery is not well studied. The aim of our study was to determine the usefulness of perioperative NT-proBNP and ACE-2 for predicting cardiac events after emergency orthopedic surgery. The perioperative NT-proBNP and ACE-2 levels were determined in 187 consecutive patients aged >60 years who underwent orthopedic surgery with 1 year of follow-up for any cardiac complications (defined as acute myocardial infarction, congestive cardiac failure, atrial fibrillation, or major arrhythmia) and death. Of the 187 patients, 20 (10.7%) sustained an in-hospital postoperative cardiac complication. The total all-cause in-hospital and 1-year mortality rate was 1.6% (3 of 187) and 8.6% (16 of 187), respectively. The median preoperative and postoperative NT-proBNP level was greater in patients who sustained an in-hospital cardiac event than in those who had not (386 vs 2,273 pg/ml, p <0.001, and 605 vs 4,316 pg/ml, p <0.001, respectively). Similarly, the postoperative median ACE-2 levels were significantly greater in the patients with an in-hospital cardiac event than in those without (25.3 vs 39.5 pmol/ml/min, p = 0.012). A preoperative NT-proBNP level of ≥741 pg/ml (odds ratio 4.5, 95% confidence interval 1.3 to 15.2, p = 0.017), postoperative troponin elevation (odds ratio 4.9, 95% confidence interval 1.3 to 18.9, p = 0.022), and number of co-morbidities (odds ratio 1.8, 95% confidence interval 1.2 to 2.8, p = 0.009) independently predicted in-hospital cardiac complications on multivariate analysis. The pre- and postoperative NT-proBNP level independently predicted 1-year cardiovascular complications but not the ACE-2 levels. In conclusion, elevated perioperative NT-proBNP predicted in-hospital and 1-year cardiac events in an emergency orthopedic population but the ACE-2 levels did not, which requires additional study for validation.

Cardiac injury and troponin testing after orthopaedic surgery.

BACKGROUND: Cardiac injury after orthopaedic surgery is an increasing problem particularly in an ageing population. The detection of cardiac injury has been aided by the use of cardiac troponins which has also raised questions about the utility of this enzyme in the post-operative setting. OBJECTIVE: This review evaluates the diagnosis and pathophysiology of myocardial infarction after orthopaedic surgery and examines how myocardial injury is detected, with particular emphasis on the role of troponin testing. SUBJECTS: Eight recent orthopaedic trials evaluating the use of troponin were identified in the literature and included in this review. RESULTS: This review found that the diagnosis of myocardial infarction ismore difficult after surgery since classic symptoms may be atypical or absent. Therefore, there ismore reliance on the typical rise and fall in troponin to diagnose cardiac injury especially because electrocardiograph changes may be hard to detect. The pathophysiology of ischaemia after orthopaedic surgery may be different to ischaemia in the non-surgical setting. The incidence of troponin elevation is between 22 and 52.9% after emergency orthopaedic operations. Of note, patients sustaining a troponin elevation are often asymptomatic. Small studies have found troponin to be a prognostic marker of in-hospital cardiac complications, increased length of stay, increased likelihood of discharge to residential care and death at 1 year. No interventional studies have been published to date. CONCLUSION: Cardiac injury is an important complication after orthopaedic surgery. Studies have found that troponin testing can detect asymptomatic cardiac injury. These patients are at risk of poorer outcomes and future research should be directed towards treatment of these patients.

Usefulness of N-terminal pro-brain natriuretic peptide to predict postoperative cardiac complications and long-term mortality after emergency lower limb orthopedic surgery.

After emergency orthopedic-geriatric surgery, cardiac complications are an important cause of morbidity and mortality. The utility of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) for the prediction of cardiac complications and mortality was evaluated. NT-pro-BNP was tested pre- and postoperatively in 89 patients >60 years of age. They were followed for 2 years for cardiac complications (defined as acute myocardial infarction, congestive cardiac failure, atrial fibrillation or major arrhythmia) or death. Receiver operating characteristic curves were constructed to determine the optimal discriminatory level for cardiac events and death using NT-pro-BNP. Twenty-three patients (25.8%) sustained an in-hospital postoperative cardiac complication. Total all-cause mortality was 3 of 89 (3.4%) in hospital, 21 of 89 (23.6%) at 1 year, and 27 of 89 (30.3%) at 2 years. Median preoperative and postoperative NT-pro-BNP levels were higher in patients who had an in-hospital cardiac event compared to those without (387 vs 1,969 pg/ml, p <0.001; and 676 vs 7,052 pg/ml, p <0.001 respectively). The optimal discriminatory level for preoperative NT-pro-BNP was 842 pg/ml and that for postoperative NT-pro-BNP was 1,401 pg/ml for the prediction of in-hospital cardiac events and 1- and 2-year mortality. Preoperative NT-pro-BNP >/=842 pg/ml (odds ratio 11.6, 95% confidence interval 2.1 to 65.0, p = 0.005) was an independent predictor of in-hospital cardiac complications using multivariate analysis and pre- and postoperative NT-pro-BNP levels were independent predictors of 2-year cardiovascular events. Patients who had preoperative NT-pro-BNP >/=842 pg/ml or postoperative NT-pro-BNP >/=1,401 pg/ml had significantly worse survival using log-rank testing (p <0.001) and these variables independently predicted 2-year mortality. In conclusion, increase pre- and postoperative NT-pro-BNP levels are independent predictors of in-hospital cardiac events and 1- and 2-year mortality in older patients undergoing emergency orthopedic surgery.

Troponin I and NT-proBNP (N-terminal pro-brain natriuretic peptide) do not predict 6-month mortality in frail older patients undergoing orthopedic surgery.

OBJECTIVES: To determine if troponin I and NT-proBNP were predictors of 6-month mortality after emergency orthopedic-geriatric surgery in a frail population. DESIGN: Prospective observational study. SETTING: Orthopedic-geriatric unit of a metropolitan hospital in Australia. PARTICIPANTS: A total of 383 patients were screened; 44 were eligible for this study of which 33 patients consented who were receiving high-level care or had severe dementia or an illness with a prognosis of less than 12 months. MEASUREMENTS: Troponin I and NT-proBNP were tested on one preoperative sample and at least one postoperative blood sample. Cardiac events were defined as acute myocardial infarction, congestive cardiac failure, new onset or rapid atrial fibrillation, major arrhythmia, or cardiac arrest. RESULTS: The mean age of the patients was 85.8 +/- 9.6 years and 93.9% had a fractured neck of femur. Premorbid cardiac conditions were common (24.2% had ischemic heart disease and 21.2% congestive cardiac failure). A third of patients had a preoperative troponin elevation and 60.6% had a postoperative elevation. The mortality within 30 days of surgery was 15.2% (5/33 patients), rising to 39.4% (13/33) at 6 months with 46.2% (6/13) dying of a cardiac cause. The Kaplan-Meier survival curve was not significantly different between patients with and without a troponin elevation. A third of patients sustained a cardiac event at 6 months. The median preoperative NT-proBNP was 1651.50 pg/L, range 25 to 31,227, and median postoperative NT-proBNP was 3038.50pg/L, range 44 to 27,348. Troponin I and NT pro-BNP did not predict 6-month mortality or cardiac complications. Predictors of 6-month mortality using univariate analysis were number of comorbidities OR 2.0 (95% CI 1.1-3.8, P = .033) and premorbid atrial fibrillation OR 7.7 (95% CI 1.2-47.8, P = .028). CONCLUSION: Troponin I and NT-proBNP were not predictors of 6-month mortality or cardiac events in an older frailer population of patients undergoing orthopedic surgery. These patients sustained substantial cardiac morbidity and mortality at 6 months after surgery. The control of symptoms, rather than prolongation of life with cardiological intervention, may be more appropriate for this patient group.

Orthopaedic-geriatric models of care and their effectiveness.

Different types of orthopaedic geriatric units have been established. This review evaluates the effectiveness of this model of care. A computerised literature search was undertaken using Medline (January 1966-February 2009), Cochrane and CINAHL with the search terms orthopaedics, geriatrics, aged, orthopaedic procedures and fractures. Relevant articles were evaluated and appraised with particular focus on randomised controlled trials. Orthopaedic-geriatric models can be divided according to the setting of care (i) acute inpatient orthopaedic-geriatric care; (ii) subacute rehabilitation; and (iii) community-based rehabilitation. Studies have been heterogenous in nature and outcomes measured have differed making pooled data analysis difficult. In general, there is a trend to effectiveness in outcomes such as functional recovery, length of stay, complications and mortality and importantly studies have not shown detrimental consequences. However, because of the varied types of interventions and models of care, it is difficult to draw firm conclusions about the effectiveness of these programs.

Incidence of post-operative troponin I rises and 1-year mortality after emergency orthopaedic surgery in older patients.

OBJECTIVES: to determine the incidence of post-operative troponin I rises and its association with 1-year all-cause mortality and cardiac events after emergency orthopaedic-geriatric surgery, which has not been studied before. METHODS: one hundred and two patients over the age of 60 were recruited and followed up at 1 year. All consented to serial troponin I measurements peri-operatively. RESULTS: the incidence of a troponin I rise post-operatively was 52.9%. Post-operative acute myocardial infarction was diagnosed in 9.8% and at 1 year, 70% of these patients were dead. At 1 year, 32.4% (33/102) had sustained a cardiac event (myocardial infarction, congestive cardiac failure, atrial fibrillation or major arrhythmia) and using multivariate analysis, post-operative troponin rise (OR 3.9, 95% CI 1.4-10.7, P = 0.008) was an independent predictor of this. Half of the patients with a troponin rise had a cardiac event compared to 18.8% without a rise. All-cause mortality was 20.6% at 1 year; 37% with an associated post-operative troponin rise died versus 2.1% without a rise (P < 0.0001). Using multivariate analysis, only two factors were associated with 1-year all-cause mortality: post-operative troponin rise (OR 12.0, 95% CI 1.4-104.8, P = 0.025) and sustaining a post-operative in-hospital cardiac event (OR 6.6, 95% CI 1.7-25.6, P = 0.006). Furthermore, patients with higher troponin levels had significantly worse survival. CONCLUSIONS: there is a high incidence of post-operative troponin I rises in older patients undergoing emergency orthopaedic surgery with 1-year mortality and cardiac events being significantly increased in these patients. Future studies are needed to determine whether any intervention can improve outcome for these patients.

Pneumonia in the elderly: a review of severity assessment, prognosis, mortality, prevention, and treatment.

Pneumonia is an increasingly common disease in the elderly due to an aging population. This is a comprehensive literature review outlining the severity assessment, morbidity, mortality, prevention and treatment options. Several models have been postulated to predict severity assessment and prognosis in older patients. Mortality increases with age and functional status is also an independent predictor for short- and long-term mortality. The effectiveness of the pneumococcal vaccine is controversial, whereas the influenza vaccine is universally recommended. Treatment involves antibiotics with the type and method depending on the severity of the pneumonia. However, treatment of nursing home patients is challenging and there are no validated guidelines at present to determine when transfer to the hospital is necessary.

Pneumonia in the elderly: a review of the epidemiology, pathogenesis, microbiology, and clinical features.

Pneumonia is a common and important disease in the elderly. The incidence is expected to rise as the population ages, and, therefore, it will become an increasingly significant problem in hospitals and the community. A comprehensive literature review was performed in order to look at the characteristics of pneumonia in the elderly population. In particular, the epidemiology, etiology and pathogenesis--including risk factors, microbiology, and clinical features--were evaluated. While aging causes physiological changes which make elderly patients more susceptible to pneumonia, it was found that comorbidities, rather than age, are also an important risk factor. The most common micro-organism responsible for pneumonia is Streptococcus pneumoniae, but other organisms need to be considered, depending on the environment of presentation. Elderly patients are more likely than younger adults to present with an absence of fever and an altered mental state. Nursing home residents tend to present with more atypical and less characteristic symptoms.