Urban environment and physical activity and capacity in patients with chronic obstructive pulmonary disease.

BACKGROUND: Physical activity and exercise capacity are key prognostic factors in chronic obstructive pulmonary disease (COPD) but their environmental determinants are unknown. OBJECTIVES: To test the association between urban environment and objective physical activity, physical activity experience and exercise capacity in COPD. METHODS: We studied 404 patients with mild-to-very severe COPD from a multi-city study in Catalonia, Spain. We measured objective physical activity (step count and sedentary time) by the Dynaport MoveMonitor, physical activity experience (difficulty with physical activity) by the Clinical visit-PROactive (C-PPAC) instrument, and exercise capacity by the 6-min walk distance (6MWD). We estimated individually (geocoded to the residential address) population density, pedestrian street length, slope of terrain, and long-term (i.e., annual) exposure to road traffic noise, nitrogen dioxide (NO2) and particulate matter (PM2.5). We built single- and multi-exposure mixed-effects linear regressions with a random intercept for city, adjusting for confounders. RESULTS: Patients were 85% male, had mean (SD) age 69 (9) years and walked 7524 (4045) steps/day. In multi-exposure models, higher population density was associated with fewer steps, more sedentary time and worse exercise capacity (-507 [95% CI: 1135, 121] steps, +0.2 [0.0, 0.4] h/day and -13 [-25, 0] m per IQR). Pedestrian street length related with more steps and less sedentary time (156 [9, 304] steps and -0.1 [-0.1, 0.0] h/day per IQR). Steeper slope was associated with better exercise capacity (15 [3, 27] m per IQR). Higher NO2 levels related with more sedentary time and more difficulty in physical activity. PM2.5 and noise were not associated with physical activity or exercise capacity. DISCUSSION: Population density, pedestrian street length, slope and NO2 exposure relate to physical activity and capacity of COPD patients living in highly populated areas. These findings support the consideration of neighbourhood environmental factors during COPD management and the attention to patients with chronic diseases when developing urban and transport planning policies.

Roles of the physical environment in health-related quality of life in patients with chronic obstructive pulmonary disease.

RATIONALE: Many clinical and psychological factors are known to influence the health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD). However, research on whether environmental factors, such as air pollution, noise, temperature, and blue/green spaces also influence HRQL in COPD has not been systematically investigated. OBJECTIVE: To assess the relationship between air pollution, road traffic noise, temperature, and distance to blue/green spaces and respiratory-specific HRQL in COPD. METHODS: We used cross-sectional data from a multicenter study in 407 stable mild-to-very severe COPD patients from Barcelona (Catalonia). Patients answered the COPD Assessment Test (CAT) and Clinical COPD Questionnaire (CCQ). Individual residential exposure to air pollutants (nitrogen dioxide [NO2] and particulate matters of varying aerodynamic diameters [PM2.5, PM10, and PM2.5absorbance]), road traffic noise (Lden), and land surface temperature were estimated using long-term averages from land-use regression models, 24-h noise maps, and land surface temperature maps, respectively. We measured residential distances to blue/green spaces from the Urban Atlas. We used mixed-effect negative binomial (for CAT) and linear (for CCQ) regression models, adjusted for potential confounders, with a random effect by center. RESULTS: Of those patients, 85 % were male and had a mean (SD) age of 69 (9) years, CAT score of 12 (7), CCQ-total score of 1.4 (1.0), and post-bronchodilator forced expiratory volume in 1 s (FEV1) of 57 (18) %predicted. We found that NO2 and PM2.5absorbance were associated with worsened CAT and CCQ-mental scores, e.g., 0.15-unit change in CAT score [regression coefficient (ß) = 0.15; 95 % confidence interval (CI) = 0.03, 0.26] per interquartile range in NO2 [13.7 µg/m3]. Greater distances to blue/green spaces were associated with worsened CCQ-mental scores [0.08; 0.002, 0.15]. CONCLUSIONS: Our study showed that increased air pollution, particularly NO2 and PM2.5absorbance and greater distances to blue/green spaces negatively influence HRQL in COPD patients. These findings have important implications for the WHO promotion to develop healthy cities for our future.

Patterns of Physical Activity Progression in Patients With COPD / Patrones de progresión de la actividad física en pacientes con EPOC

Introduction: Although mean physical activity in COPD patients declines by 400•500steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants.Methods: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns.Results: In 291 COPD patients (mean±SD 68±8 years, 81% male, FEV1 59±19%pred) we identified three distinct physical activity progression patterns: Inactive (n=173 [59%], baseline: 4621±1757 steps/day, 12-month change (΢): ∧487±1201 steps/day), ActiveImprovers (n=49 [17%], baseline: 7727±3275 steps/day, ΢:+3378±2203 steps/day) and ActiveDecliners (n=69 [24%], baseline: 11 267±3009 steps/day, ΢: ∧2217±2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90•0.98] per 10m, P=.001) and a higher mMRC dyspnea score (1.71 [1.12•2.60] per 1 point, P=.012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver.Conclusions: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline. (AU)

Introducción: Aunque la actividad física en pacientes con EPOC declina una media anual de 400-500 pasos/día, se desconoce si esta progresión es igual en todos los pacientes. Este estudio pretendió identificar los patrones de progresión de la actividad física mediante métodos libres de hipótesis y evaluar sus determinantes.Métodos: Se estudiaron 291 pacientes con EPOC estable (media±DE: 68±8años, 81% hombres, VEMS 59±19%pred) de dos cohortes europeas con actividad física basal y a 12meses (acelerómetro Dynaport MoveMonitor). Se identificaron conglomerados (patrones) de progresión de actividad física basados en los niveles y cambios de pasos/día usando k-means, y se compararon entre patrones las características sociodemográficas, interpersonales, ambientales, clínicas y psicosociales basales.Resultados: Se identificaron tres patrones: inactivo (n=173 [59%], basal: 4.621±1.757 pasos/día, cambio en 12meses (΢): ∧487±1.201 pasos/día), activo que aumenta (n=49 [17%], basal: 7.727±3.275 pasos/día, ΢: +3.378±2.203 pasos/día) y activo que reduce (n=69 [24%], basal: 11.267±3.009 pasos/día, ΢: ∧2.217±2.085 pasos/día). La distancia en la prueba de la marcha de 6minutos (6MWD) y la disnea se asociaron independientemente con ser inactivo: RRR [IC95%] 0,94 [0,90-0,98] por cada 10m de 6MWD (p=0,001) y 1,71 [1,12-2,60] por cada punto en la escala mMRC (p=0,012), respectivamente, en comparación con el patrón activo que reduce. No se encontraron variables basales independientemente asociadas con ser activo que aumenta.Conclusiones: La progresión natural de la actividad física en pacientes con EPOC es heterogénea. Mientras que el patrón de pacientes inactivo se relaciona con peores características clínicas de EPOC, no se pudo predecir la evolución de los activos a aumentar o reducir. (AU)

Patterns of Physical Activity Progression in Patients With COPD.

INTRODUCTION: Although mean physical activity in COPD patients declines by 400-500steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants. METHODS: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns. RESULTS: In 291 COPD patients (mean±SD 68±8 years, 81% male, FEV1 59±19%pred) we identified three distinct physical activity progression patterns: Inactive (n=173 [59%], baseline: 4621±1757 steps/day, 12-month change (Δ): -487±1201 steps/day), ActiveImprovers (n=49 [17%], baseline: 7727±3275 steps/day, Δ:+3378±2203 steps/day) and ActiveDecliners (n=69 [24%], baseline: 11 267±3009 steps/day, Δ: -2217±2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90-0.98] per 10m, P=.001) and a higher mMRC dyspnea score (1.71 [1.12-2.60] per 1 point, P=.012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver. CONCLUSIONS: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline.

Determinants of study completion and response to a 12-month behavioral physical activity intervention in chronic obstructive pulmonary disease: A cohort study.

OBJECTIVES: Physical activity is key to improve the prognosis of chronic obstructive pulmonary disease (COPD). To help to tailor future interventions we aimed to identify the baseline characteristics of COPD patients which predict 12-month completion and response to a behavioral physical activity intervention. METHODS: This is a 12-month cohort study of the intervention arm of the Urban Training randomized controlled trial (NCT01897298), an intervention proven to be efficacious to increase physical activity. We considered baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics as potential determinants of completion and response. We defined completion as attending the 12-month study visit. Among completers, we defined response as increasing physical activity ≥1100 steps/day from baseline to 12 months, measured by accelerometer. We estimated the factors independently for completion and response using multivariable logistic regression models. RESULTS: Of a total of 202 patients (m (SD) 69 (9) years, 84% male), 132 (65%) completed the study. Among those, 37 (28%) qualified as responders. Higher numbers of baseline steps/day (OR [95% CI] 1.11 [1.02-1.21] per increase of 1000 steps, p<0.05) and living with a partner (2.77 [1.41-5.48], p<0.01) were related to a higher probability of completion while more neighborhood vulnerability (0.70 [0.57-0.86] per increase of 0.1 units in urban vulnerability index, p<0.01) was related to a lower probability. Among the completers, working (3.14 [1.05-9.33], p<0.05) and having an endocrino-metabolic disease (4.36 [1.49-12.80], p<0.01) were related to a higher probability of response while unwillingness to follow the intervention (0.21 [0.05-0.98], p<0.05) was related to a lower probability. CONCLUSIONS: This study found that 12-month completion of a behavioral physical activity intervention was generally determined by previous physical activity habits as well as interpersonal and environmental physical activity facilitators while response was related to diverse factors thought to modify the individual motivation to change to an active lifestyle.

The First Case(s) of Botulism in Vienna in 21 Years: A Case Report.

UNLABELLED: We describe two linked cases of botulinum toxin intoxication to provide the clinician with a better idea about how botulism cases may present since early diagnosis and treatment are crucial in botulism. Botulinum toxin is the strongest neurotoxin known. METHODS: We review the available literature, the compiled clinical data, and observations. RESULTS: After a slow onset of clinical signs a married couple living in Vienna presented with dysphagia, difficulties in accommodation, inability to sweat, urinary and stool retention, dizziness, and nausea. They suffered intoxication with botulinum toxin type B. Botulism is a rarely occurring disease in Austria. In the last 21 years there were only twelve reported cases. CONCLUSION: Both patients went to a general practitioner as well as several specialists before they were sent to and correctly diagnosed at our outpatient department. To avoid long delays between intoxication and diagnosis we think it is crucial to advert to the complex symptoms a nonsevere intoxication with botulinum toxin can produce, especially since intoxications have become rare occurrences in the industrialized societies due to the high quality of industrial food production.

Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha as acne inversa therapy.

We present a case of fever, brain abscesses, and Gemella morbillorum bacteremia after anti-tumor necrosis factor alpha (TNF-α) therapy in a 21-year-old acne inversa patient currently taking long-term dapsone. To the best of our knowledge, this is the first report describing such a case. During antimicrobial therapy, the patient developed systemic varicella infection with severe thrombocytopenia.

Effect of cooling after human cardiac arrest on myocardial infarct size.

AIMS: The Hypothermia after Cardiac Arrest (HACA) trial assessed whether mild therapeutic hypothermia improved the rate of good neurological recovery in patients after ventricular fibrillation cardiac arrest of presumed cardiac origin. We evaluated the impact of hypothermia on myocardial injury. METHODS: Re-analysis of a HACA trial subset for our department (cooling, n=55; controls, n=56). Plasma levels of CK, CKMB and ST-scores were used as a measure of infarct size. RESULTS: Area under the curve (AUC) for CK was 28,786U/l x 24 h (IQR 5646-44,998) in the cooling group and 20,373U/l x 24 h (IQR 8211-30,801) for controls (p=0.40), for CKMB AUC was 1691U/l x 24 h (IQR 724-3330) and 1187U/l x 24 h (IQR 490-2469), respectively (p=0.18). The ST score was -40% (IQR [-55]-[+16]) in the cooling group (n=23) and -22% (IQR [-84]-[+33]) for controls (n=24) (p=0.76). When the cooling group was stratified into early (< or =8h) and longer (>8h) time to target temperature, the early group displayed a significantly lower CK 7340U/l x 24 h (IQR 3921-33,753) vs. 38,986U/l x 24 h (IQR 23,945-57,514, p=0.007) and a lower CKMB. CONCLUSION: Cooling after successful resuscitation for ventricular fibrillation cardiac arrest did not influence infarct size. Cautious interpretation of the subgroup analysis may indicate a favourable trend for early cooling.

Cardiac arrest in public locations--an independent predictor for better outcome?

OBJECTIVE: Outcome after cardiac arrest is known to be influenced by immediate access to resuscitation. We aimed to analyse the location of arrest in relation to the prognostic value for outcome. DESIGN: Retrospective review from prospective databases (ambulance routine documentation database and emergency department database on patients treated for cardiac arrest). SETTING: Vienna (1.7 million inhabitants) ambulance service and tertiary care facility (university clinics). PATIENTS: Two independent cohorts: (1) a population-based cohort of patients who were treated for cardiac arrest by the municipal ambulance service outside the hospital. The endpoint in this group was survival to hospital admission with spontaneous circulation. (2) A cohort of patients who were admitted to the emergency department after successful out of hospital resuscitation. The endpoint in this group was survival to 6 months with good neurological status (best Cerebral Performance Category 1 or 2 within 6 months). MEASUREMENTS: We analysed whether the location of non-traumatic adult out-of-hospital cardiac arrest (public versus private place) was a predictor for good outcome. RESULTS: PATIENTS who had cardiac arrest in a public location were more likely to arrive in hospital alive (39% versus 31%, crude OR 1.4, 95% CI 1.001-1.975, p=0.049) and were more likely to have a good neurological outcome after 6 months (35% versus 25%, crude OR 1.65, adjusted OR 1.59, 95% CI 1.07-2.36, p=0.023), compared to patients who had cardiac arrest in a non-public location. CONCLUSION: Cardiac arrest in a public location is independently associated with a better outcome.

Dynamics of inflammation parameters prior to tachyarrhythmias in critically ill patients.

BACKGROUND: The aim of this study was to assess the dynamics of inflammation parameters prior to a tachyarrhythmic event in critically ill patients. We evaluated the course of inflammation parameters over 48 hours before the occurrence of tachyarrhythmias. METHODS: Prospective observational study conducted at a cardiologic medical-postoperative tertiary intensive care unit at the Vienna university hospital. Between November 1996 and July 1999 all consecutive patients (n = 756) were screened for the occurrence of arrhythmias. Patients with sustained tachyarrhythmias (n = 119) form the basis of the report. The tachyarrhythmia episodes were related to the evolution of C-reactive protein, leukocytes and fibrinogen during the 48 hours before the arrhythmic event. RESULTS: A total of 278 tachyarrhythmia episodes was identified (wide QRS complex tachycardia, n = 168; narrow QRS complex tachycardia, n = 108; ventricular fibrillation, n = 2). The body temperature on the day of arrhythmia was 37.4 +/- 1 degrees C. Overall, there was no statistically significant change in any inflammation parameter within 48 hours prior to tachyarrhythmias (C-reactive protein: 17.4 +/- 12 [-48 h], 16.2 +/- 11 [-24 h], 15.2 +/- 12 [0 h] mg/dl, p = 0.2). When stratifying for different levels of C-reactive protein on the day of arrhythmia, the trend was inhomogenous. For lower strata, values were significantly decreasing towards arrhythmias; for higher strata, an increase in C-reactive protein was observed (stratum A: 8.5 +/- 7.2 [-48 h], 6.6 +/- 4.9 [-24 h], 4.8 +/- 2.9 mg/dl [0 h], p = 0.0001; stratum B: 16.0 +/- 7.1 [-48 h], 13.8 +/- 6.0 [-24 h], 14.4 +/- 2.6 mg/dl [0 h], p = 0.09; stratum C: 21.2 +/- 7.4 [-48 h], 21.5 +/- 7.5 [-24 h], 24.9 +/- 3.0 mg/dl [0 h], p = 0.008; stratum D: 34.3 +/- 13.4 [-48 h], 35.7 +/- 9.0 [-24 h], 39.7 +/- 5.5 mg/dl [0 h], p = 0.13). CONCLUSION: In this group of critically ill patients inflammation parameters did not change significantly during the 48 hours prior to the arrhythmic event. For different levels of C-reactive protein at the time of arrhythmia, no clear dynamics of inflammatory signs were observed.

Arterial puncture closing devices compared with standard manual compression after cardiac catheterization: systematic review and meta-analysis.

CONTEXT: Arterial puncture closing devices (APCDs) were developed to replace standard compression at the puncture site and to shorten bed rest following percutaneous coronary intervention. OBJECTIVE: To assess the safety and efficacy of APCDs (Angioseal, Vasoseal, Duett, Perclose, Techstar, Prostar) compared with standard manual compression in patients undergoing coronary angiography or percutaneous vascular interventions. DATA SOURCES: A systematic literature search of MEDLINE (1966-January 2003), EMBASE (1989-January 2003), PASCAL (1996-January 2003), BIOSIS (1990-January 2003), and CINHAL (1982-January 2003) databases and the Cochrane Central Register of Controlled Trials for relevant articles in any language. STUDY SELECTION: Included randomized controlled trials reporting vascular complications at the puncture site (hematoma, bleeding, arteriovenous fistula, pseudoaneurysm) and efficacy (time to hemostasis, time to ambulation, time to discharge from hospital). DATA EXTRACTION: Two reviewers abstracted the data independently and in duplicate. Disagreements were resolved by discussion among at least 3 reviewers. The most important criteria were adequacy of allocation concealment, whether the analysis was according to the intention-to-treat principle, and if person assessing the outcome was blinded to intervention group. Random-effects models were used to pool the data. DATA SYNTHESIS: Thirty trials met the selection criteria and included up to 4000 patients. When comparing any APCD with standard compression, the relative risk (RR) of groin hematoma was 1.14 (95% confidence interval [CI], 0.86-1.51; P =.35); bleeding, 1.48 (95% CI, 0.88-2.48; P =.14); developing an arteriovenous fistula, 0.83 (95% CI, 0.23-2.94; P =.77); and developing a pseudoaneurysm at the puncture site, 1.19 (95% CI, 0.75-1.88; P =.46). Time to hemostasis was shorter in the group with APCD compared with standard compression (mean difference, 17 minutes; range, 14-19 minutes), but there was a high degree of heterogeneity among studies. Only 2 studies explicitly reported allocation concealment, blinded outcome assessment, and intention-to-treat analysis. When limiting analyses to only trials that used explicit intention-to-treat approaches, APCDs were associated with a higher risk of hematoma (RR, 1.89; 95% CI, 1.13-3.15) and a higher risk of pseudoaneurysm (RR, 5.40; 95% CI, 1.21-24.5). CONCLUSIONS: Based on this meta-analysis of 30 randomized trials, many of poor methodological quality, there is only marginal evidence that APCDs are effective and there is reason for concern that these devices may increase the risk of hematoma and pseudoaneurysm.

Short versus prolonged bed rest after uncomplicated acute myocardial infarction: a systematic review and meta-analysis.

BACKGROUND: Recently updated guidelines by the American College of Cardiology/American Heart Association and the European Society of Cardiology recommend at least 12 hours bed rest in patients with uncomplicated myocardial infarction. METHODS: We performed a systematic literature review and meta-analysis of randomized and quasi-randomized controlled trials comparing short versus prolonged bed rest in patients with uncomplicated acute myocardial infarction. RESULTS: We found 15 trials with 1332 patients assigned to a short period of bed rest (range 2 to 12 days) and 1326 patients assigned to prolonged bed rest (range 5 to 28 days). Generally, the studies were outdated and seemed to be of poor methodologic reporting quality. There was no evidence that shorter bed rest was more harmful than longer bed rest in terms of death, reinfarction, post-infarction angina, or thromboembolic events. CONCLUSION: We concluded that bed rest ranging from 2 to 12 days seems to be as safe as longer periods of bed rest.

Plasma concentrations of von Willebrand factor and intracellular adhesion molecule-1 for prediction of outcome after successful cardiopulmonary resuscitation.

OBJECTIVE: Ischemia/reoxygenation following cardiopulmonary resuscitation might cause endothelial injury/activation that could contribute to an adverse outcome after cardiopulmonary resuscitation. We studied plasma concentrations of von Willebrand factor (vWF) antigen and soluble intracellular adhesion molecule (sICAM)-1 as markers of a generalized endothelial injury/activation in relation to outcome after cardiopulmonary resuscitation. DESIGN: Retrospective study on stored plasma samples. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty-five patients who survived >24 hrs after in- or out-of-hospital cardiopulmonary resuscitation and 15 noncritically ill control patients.I NTERVENTIONS: Blood sampling. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of vWF antigen and sICAM-1 on day 2 after cardiopulmonary resuscitation were higher in patients than in controls (p < .001 and p = .001, respectively). In-hospital cardiopulmonary resuscitation, cardiopulmonary resuscitation duration > or = 15 mins, severe cardiovascular failure, and renal dysfunction/failure at the time of blood sampling were associated with significant elevations in vWF antigen and sICAM-1 concentrations. Patients with an unfavorable outcome after cardiopulmonary resuscitation (cerebral performance category > or = 3) exhibited higher vWF antigen and sICAM-1 concentrations than patients with good outcome (cerebral performance category 1-2; p < .001 and p = .097, respectively). Renal dysfunction/failure, severe cardiovascular failure, systemic inflammatory response syndrome, and cardiopulmonary resuscitation duration > or = 15 mins were also associated with higher adverse outcome rates. Combination of these four variables into a cardiac arrest risk score (levels 0-4) showed adverse outcome rates of 100, 56, and 0% in patients with arrest scores of 4, 2-3, and 0-1, respectively. A vWF antigen concentration >166% was an independent predictor of outcome after cardiopulmonary resuscitation (p = .002) and was associated with increased adverse outcome rates in patients with cardiac arrest risk scores of 2-3. Furthermore, both vWF antigen concentrations >166% and sICAM-1 concentrations >500 ng/mL had 100% specificity for an adverse outcome in patients after out-of-hospital cardiopulmonary resuscitation but were less predictive in patients after in-hospital cardiopulmonary resuscitation. CONCLUSIONS: vWF antigen and sICAM-1 might be useful adjunctive variables for early determination of outcome in patients after successful out-of-hospital cardiopulmonary resuscitation.

Predictors of survival in unselected patients with acute myocardial infarction requiring continuous catecholamine support.

BACKGROUND: Several predictors of survival have been described in selected subgroups of patients suffering from acute myocardial infarction. However, data on unselected patients with acute myocardial infarction and cardiogenic shock, including patients with out-of hospital cardiac arrest, are missing. We aimed to assess predictors of survival for an unselected cohort of patients representative of clinical practice who experienced acute myocardial infarction and required continuous catecholamine support for circulatory failure. METHODS: The study was performed at a 2000 bed university hospital. All consecutive patients admitted to our emergency department with acute myocardial infarction were prospectively enrolled in a clinical trial from 1993 to 2000. DESIGN: A retrospective cohort study was performed on patients with myocardial infarction requiring catecholamine support within the first 24 h. Primary endpoint was in-hospital mortality. RESULTS: The analysis was carried out on 262 patients, 189 men (72%), median age 65 years (IQR 53-73). Out-of-hospital cardiac arrest was reported in 47% (122/262). In-hospital mortality was 53% (138/262). Survivors as compared to non-survivors exhibited significant differences with respect to age (60 vs. 68 years, P<0.0001), systolic and diastolic blood pressure on admission (110 vs. 102 mmHg, P=0.01 and 64 vs. 58 mmHg, P=0.006, respectively), initial blood serum lactate (6.8 vs. 8.3, P=0.01), peak CKMB level (93 vs. 138 U/l, P=0.005), use of adrenaline (epinephrine) (38 vs. 68%, P<0.0001) and any attempt of revascularisation (76 vs. 63%, P=0.03). In a multivariate model younger age [OR 1.06 (CI 1.03-1.10), P<0.001], no use of adrenaline [OR 2.63 (CI 1.35-5.26) P=0.005] and lower peak CKMB [OR 1.01 (CI 1.01-1.01), P<0.0001] were independently associated with in-hospital survival. CONCLUSION: In unselected patients including CPR survivors with acute myocardial infarction requiring continuous catecholamine support, younger age, the absence of continuous adrenaline administration and a lower peak CKMB were independently associated with increased in-hospital survival.

Multiple organ failure in patients with cardiogenic shock is associated with high plasma levels of interleukin-6.

OBJECTIVE: In patients with septic shock, multiple organ failure (MOF) is associated with high levels of interleukin-6 (IL-6). Although organ failure is also a common complication of cardiogenic shock (CS), IL-6 levels have been reported to be lower in patients with CS than in patients with septic shock. We studied IL-6 plasma levels in patients with CS with respect to organ failure. SETTING: Eight-bed intensive care unit at a university hospital. PATIENTS: Fifty-one patients with CS, 26 patients with septic shock, and 11 noncritically ill controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with CS had higher IL-6 levels than noncritically ill controls ( p<.001) but lower levels than patients with septic shock ( p=.003). CS patients with MOF at the time of blood sampling exhibited, however, higher IL-6 levels than CS patients without organ failure, and IL-6 levels in patients with CS correlated to the total Sepsis-related Organ Failure Assessment score at the time of blood sampling ( r=.57, <.001). No significant differences in IL-6 levels were found when comparing CS patients with MOF at the time of blood sampling with patients with septic shock. Furthermore, CS patients who developed MOF during ICU stay exhibited significantly higher IL-6 levels than CS patients who never did develop MOF. An IL-6 level of >200 pg/mL had a 93% specificity and 100% sensitivity for the prediction of MOF in patients with CS. CONCLUSIONS: Once MOF is present, patients with CS exhibit similarly high IL-6 levels as patients with septic shock. High IL-6 levels in CS patients are associated with a progression to MOF.

Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis.

OBJECTIVE: Melatonin is involved in the regulation of the sleep-wake cycle and exhibits multiple interactions with the neuroendocrine and the immune system. Melatonin secretion in healthy individuals follows a stable circadian rhythm. Critical illness, continuous administration of drugs, and loss of external zeitgeber might impair the circadian rhythm of melatonin secretion in the intensive care unit (ICU), thereby compromising the physiologic stress-induced immune response. DESIGN: Prospective, controlled clinical study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Seventeen septic, sedated ICU patients (group A); 7 nonseptic ICU patients (group B); and 21 control patients (group C) were studied. MEASUREMENTS AND MAIN RESULTS: 6-Sulfatoxymelatonin (aMT6s) was determined from urine samples taken at 4-hr intervals over a total period of 24 hrs. aMT6s was measured by enzyme-linked immunosorbent assay. Circadian mesors, phase amplitudes, and timing of the acrophase were assessed by cosinor analysis. Differences between groups were calculated by contingency data analysis and by analysis of variance. Circadian mesors of urinary aMT6s were 3904 +/- 1597, 2622 +/- 927, and 3183 +/- 1514 ng/4 hrs in groups A, B, and C, respectively (p = NS). aMT6s exhibited significant circadian periodicity in only 1/17 (6%) patients of group A but in 6/7 (86%) patients of group B and in 18/23 (78%) patients of group C (group A vs. groups B and C: p = .0001) Phase amplitudes were markedly lower in group A (1071 +/- 1005 ng/4 hrs) compared with group B (2284 +/- 581 ng/4 hrs, p = .009) and C (2838 +/- 2255 ng/4 hrs, p = .006). The acrophase was significantly delayed in patients of group A (10:35 am +/- 255 mins) compared with group B (05:43 am +/- 114 mins, p = .01) and group C (4:20 am +/- 107 mins, p < .0001). In sepsis survivors, aMT6s excretion profiles tended to normalize, but still lacked a significant circadian rhythm at ICU discharge. CONCLUSION: The present study revealed striking abnormalities in urinary aMT6s excretion in septic ICU patients. In contrast, circadian rhythm was preserved in nonseptic ICU patients, indicating that impaired circadian melatonin secretion in septic patients is mainly related to the presence of severe sepsis and/or concomitant medication. Further investigations are required to examine the underlying pathophysiologic mechanism and the clinical implications of this finding.

Complicated infective endocarditis necessitating ICU admission: clinical course and prognosis.

AIM: To study incidence, clinical course and prognostic factors in patients admitted to medical intensive care units (ICUs) because of a complicated course of infective endocarditis. METHOD: This was a retrospective multicenter observational study of 4106 patients admitted to four medical ICUs in one tertiary hospital and one university hospital between 1994 and 1999. RESULTS: Infective endocarditis was identified in 33 (0.8%) patients. Of these, 26 were male, mean age was 59 +/- 12 and APACHE-III score was 75 +/- 31. Reasons for transfer to the ICU were congestive heart failure in 64%, septic shock in 21%, neurological deterioration in 15% and cardiopulmonary resuscitation in 9%. Inotropes or vasoconstrictors were required in 73% and multiorgan failure developed in 64% of the patients. Prosthetic valve endocarditis was present in 21%. Gram-positive cocci were found in 96% of all positive cultures; cultures were negative in 27% of the patients. Transthoracic echocardiograms were diagnostic in only 33% and transesophageal studies were required in 91% to confirm diagnosis or fully to delineate the extent of disease. Surgical intervention was performed in 60% of the patients, and the remaining 40% were only treated medically. The APACHE-III score on admission did not differ statistically between the two groups (69 +/- 30 versus 84 +/- 34, P = 0.17). In-patient mortality was 84% in patients treated medically, and 35% in surgically treated patients. Using multivariate analysis, acute renal failure on admission was identified as the independent single predictor for in-patient death (OR 5, 95% CI 1.04-24.03, P = 0.04). CONCLUSION: The prognosis for patients with infective endocarditis requiring admission to a medical ICU is serious. Nevertheless, the data suggest that surgical intervention may be successfully performed in a substantial number of patients despite the presence of severe shock and occurrence of multiorgan failure.

Prognosis of patients who develop acute renal failure during the first 24 hours of cardiogenic shock after myocardial infarction.

PURPOSE: Acute renal failure has important prognostic implications in critically ill patients, but the effects of acute renal failure on in-hospital mortality in the subset of patients with cardiogenic shock are not known. SUBJECTS AND METHODS: All consecutive patients who presented with acute coronary syndrome at our cardiovascular intensive care unit from 1993 to 2000 and who were in cardiogenic shock were enrolled. Acute renal failure was defined as a urine volume < 20 mL/h associated with an increase in serum creatinine level > or = 0.5 mg/dL or > 50% above the baseline value. RESULTS: There were 118 patients (83 men [70%]; mean [+/- SD] age, 66 +/- 10 years), 39 (33%) of whom developed acute renal failure within 24 hours after the onset of shock. In-hospital mortality was 87% (34/39) in patients with acute renal failure and 53% (42/79) in patients without acute renal failure (odds ratio [OR] = 6.0; 95% confidence interval [CI]: 2.1 to 17; P < 0.001). Other significant univariate predictors of mortality included the peak serum lactate level, epinephrine dose, and the maximum serum creatinine level. Multivariate logistic regression analysis identified acute renal failure as the only independent predictor of mortality. CONCLUSION: Acute renal failure was common in patients with cardiogenic shock and strongly associated with in-hospital mortality.

Which treatment for low back pain? A factorial randomised controlled trial comparing intravenous analgesics with oral analgesics in the emergency department and a centrally acting muscle relaxant with placebo over three days [ISRCTN09719705].

BACKGROUND: About two thirds of adults suffer from backpain at some time during their life. In the emergency room many patients with acute back pain are treated with intravenous non-steroidal analgesics. Whether this treatment is superior to oral administration of non-steroidal analgesics is unknown. Intravenous administration, however, requires considerable amounts of resources and accounts for high workload in busy clinics. In the further course centrally acting muscle relaxants are prescribed but the effectiveness remains unclear. The objective of this study is on the one hand to compare the effectiveness of intravenous with oral non-steroidal analgesics for acute treatment and on the other hand to compare the effectiveness of a centrally active muscle relaxant with placebo given for three days after presentation to the ED (emergency department). METHODS/DESIGN: This study is intended as a randomised controlled factorial trial mainly for two reasons: (1) the sequence of treatments resembles the actual proceedings in every-day clinical practice, which is important for the generalisability of the results and (2) this design allows to take interactions between the two sequential treatment strategies into account. There is a patient preference arm included because patients preference is an important issue providing valuable information: (1) it allows to assess the interaction between desired treatment and outcome, (2) results can be extrapolated to a wider group while (3) conserving the advantages of a fully randomised controlled trial. CONCLUSION: We hope to shed more light on the effectiveness of treatment modalities available for acute low back pain.