Clinical factors affecting costs in patients receiving systemic antifungal therapy in intensive care units in Greece: Results from the ESTIMATOR study.

Invasive fungal infections are common in intensive care units (ICUs) but there is a great variability in factors affecting costs of different antifungal treatment strategies in clinical practice. To determine factors affecting treatment cost in adult ICU patients with or without documented invasive fungal infection receiving systemic antifungal therapy (SAT) we have performed a prospective, multicentre, observational study enrolling patients receiving SAT in participating ICUs in Greece. During the study period, 155 patients received SAT at 14 participating ICUs: 37 (23.9%) for proven fungal infection before treatment began, 10 (6.5%) prophylactically, 77 (49.7%) empirically and 31 (20.0%) pre-emptively; 66 patients receiving early SAT (55.9%) were subsequently confirmed to have proven infection with Candida spp. (eight while on treatment). The most frequently used antifungal drugs were echinocandins (89/155; 57.4%), fluconazole (31/155; 20%) and itraconazole (20/155; 12.9%). Mean total cost per patient by SAT strategy was €20 458 (proven), €15 054 (prophylaxis), €23 594 (empiric) and €22 184 (pre-emptive). Factors associated with significantly increased cost were initial treatment failure, length of stay (LOS) in ICU before starting SAT (i.e. from admission until treatment start), fever and proven candidaemia (all P≤.05). CONCLUSION: Early administration of antifungal drugs was not a substantial component of total hospital costs. However, there was a significant adverse impact on costs with increasing LOS in febrile patients in ICU for whom diagnosis of fungaemia was delayed before starting SAT, and with initial treatment failure. Awareness of potential candidaemia and initiation of pre-emptive or empirical strategy as early appropriate treatment may improve ICU patient outcomes while reducing direct medical costs.

Management of sudden hearing loss with hyperbaric oxygen therapy.

UNLABELLED: Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as the sensorineural hearing loss of a minimum of 30 dB in at least three frequencies for three days or more. This study aims to evaluate the clinical efficacy of hyperbaric oxygen therapy (HBO2) in the management of idiopathic sudden sensorineural hearing loss. MATERIAL-METHODS: Patients with ISSHL received treatment including oral corticosteroids and HBO2. HBO2 protocol included five phases of five sessions each. ISSHL was assessed by measuring the tonal audiogram before and after each phase. Tinnitus was assessed using a questionnaire and a visual analogue scale at the beginning and the end of the study. Secondary assessment points included changes in the intensity and the improvement of tinnitus. RESULTS: 56 patients were included in the study. All patients completed Phases I and II of HBO2, 43 completed Phase III, 13 completed Phase IV, and six completed all five phases. Overall, a significant improvement was noted between the initial and final audiogram after HBO2 (p < 0.001). Tinnitus evaluation score, intensity and related problems were also significantly reduced (p < 0.001). CONCLUSION: This study affirms previous findings that the use of HBO2 and vasodilators are efficacious in the treatment of ISSHL. Our findings also suggest benefit for the treatment of tinnitus.

Temperature multiscale entropy analysis: a promising marker for early prediction of mortality in septic patients.

A few studies estimating temperature complexity have found decreased Shannon entropy, during severe stress. In this study, we measured both Shannon and Tsallis entropy of temperature signals in a cohort of critically ill patients and compared these measures with the sequential organ failure assessment (SOFA) score, in terms of intensive care unit (ICU) mortality. Skin temperature was recorded in 21 mechanically ventilated patients, who developed sepsis and septic shock during the first 24 h of an ICU-acquired infection. Shannon and Tsallis entropies were calculated in wavelet-based decompositions of the temperature signal. Statistically significant differences of entropy features were tested between survivors and non-survivors and classification models were built, for predicting final outcome. Significantly reduced Tsallis and Shannon entropies were found in non-survivors (seven patients, 33%) as compared to survivors. Wavelet measurements of both entropy metrics were found to predict ICU mortality better than SOFA, according to a combination of area under the curve, sensitivity and specificity values. Both entropies exhibited similar prognostic accuracy. Combination of SOFA and entropy presented improved the outcome of univariate models. We suggest that reduced wavelet Shannon and Tsallis entropies of temperature signals may complement SOFA in mortality prediction, during the first 24 h of an ICU-acquired infection.

Measurement of tumour necrosis factor receptors for immune response in colon cancer patients.

Immune system is crucial to tumour's initiation, progress and establishment and is contributing to prevent upcoming damaging invasion. Tumour development and surgical resection are both immunosuppressive processes. Immune response could be evaluated by ex vivo lipopolysaccharide (LPS) test, measuring cytokines and receptors release. The aim of the study is to investigate the postoperative immune recovery of cancer patients upon discharge. Twenty-two patients with colon cancer, without pre-treatment, and 16 healthy volunteers (HV) were enrolled in the study. Ten ml of whole blood were collected from every patient on admission (PRE) and upon discharge (POD7) and every HV. Diluted whole blood samples were stimulated with 500 pg/ml LPS, at 37°C, for 4H. Cell culture supernatants (CCSP) were removed after centrifugation and stored at -70°C. Tumour necrosis factor-alpha (TNF-α), interleukin-6 and interleukin-10 (IL-6, IL-10), soluble TNF receptors (sTNFRs) were measured in serum and CCSP by enzymelinked immunosorbent assay. Serum cytokines and receptors, PRE and POD7, were significantly elevated compared to HV (P < 0.001) and significant correlations were found between POD7 IL-6 and sTNFRs (Spearman's ρ 0.47, P < 0.05). Ex vivo, TNF-α, IL-6 and TNFRI release were lower either PRE or POD7, while IL-10 and TNFRII were higher, than in HV. No significant differences (P > 0.05) were found between PRE and POD7 levels in serum or CCSP. Cancer patients are not postoperatively immune restored until discharge. The trend of anti-inflammatory TNFRs release could account for alternative marker for the control of cancer patients immune response and the schedule of their following therapeutic treatment.

Immune responses during and after exercise of constant and alternating intensity above the lactate threshold.

AIM: Intense and prolonged exercise greatly affects circulating cytokine levels. The purpose of this study was to investigate the possible changes in tumour necrosis factor -a (TNF-a), interleukin 6 (IL-6) and cortisol concentrations during and after prolonged exercise of constant and alternating intensity of the same duration and total work performed. METHODS: Ten male subjects underwent two main cycling exercise trials lasting one hour each. On one occasion, exercise intensity was alternated between 46.5±1.9% of maximal oxygen uptake (VO2max ) for 40 s and 120% of VO2max for 20 s, so that the mean intensity corresponded to 105% of the lactate threshold. On the other occasion, exercise intensity was constant at 105% of the lactate threshold. Levels of TNF-a, IL-6 after lipo polysaccharide (LPS) stimulation as well as cortisol were measured at rest, 30 and 60 minutes of exercise and 1 hour after. RESULTS: No significant differences were observed in TNF-a concentrations between the two exercise protocols (P= 0.75), but there was a significant time effect (P<0.01). TNF-a was increased in both groups from a resting value of 436.1±102.5 to 649.5±187.7 pg/mL (P<0.05) at the end of exercise and was subsequently decreased 1 hour post exercise to 305.9±78.8 pg/mL (P<0.01). No significant difference in IL-6 and cortisol concentrations was observed between the two exercise protocols (P=0.13, P=0.10 accordingly). CONCLUSION: In conclusion, prolonged constant and alternating intensity exercise of the same mean intensity and duration seemed to provoke similar changes in aspects of immune response in healthy subjects.

Psychological distress and delusional memories after critical care: a literature review.

BACKGROUND: A considerable number of intensive care unit (ICU) survivors report delusional memories, which refer to dreams, nightmares, paranoid delusions and hallucinations experienced in the ICU. These memories often have a strong vividness, long duration and high emotional impact. AIM: The aim of this review was to investigate and synthesize published literature about psychological distress associated with delusional memories of adult ICU survivors. METHODS: Using key terms, a search was conducted in major health care electronic databases [Cumulative Index for Nursing and Allied Health Literature (CINAHL), PubMed, Web of Science and PsycInfo] focusing on articles published between 1990 and 2009 in English-language journals. FINDINGS: Ten articles met the inclusion criteria. Recall of delusional memories at various intervals after ICU discharge was associated with post-traumatic stress disorder (PTSD)-related symptoms in many studies, while associations with other aspects of psychological distress, mainly feelings of fear, anxiety and depression, were also reported. Recent studies did not seem to confirm the protective role of factual memories. CONCLUSIONS: The findings support the association between delusional memories and PTSD-related symptoms, but further research is needed to confirm their association with other psychological disorders. Development of a safety sense in the ICU can protect patients against the emotional impact of both delusional and stressful factual ICU memories. Appropriate follow-up of high-risk patients could improve their long-term psychological recovery.

Cardiopulmonary resuscitation in end-stage cancer patients.

Cardiopulmonary resuscitation (CPR) in patients with end-stage cancer is an issue of significant clinical and ethical importance. In general, the overall survival to discharge in cancer patients is referred to be 6.2% (localised - 9.5% vs. metastatic disease - 5.6%) compared to 15% of unselected in-hospital arrests. However, immediate survival, as well as survival to discharge after a successful CPR is affected by multiple factors. Type and extend of tumor, degree of clinical deterioration, functional status and many other factors do correlate with outcome in different degrees. Critical illness scoring systems are commonly used in order to assess performance status of patients and predict outcome. This article will review all the above mentioned factors, as well as patients' perception about "do-not-resuscitate" orders and palliative care.

Penetration of colistin into cerebrospinal fluid.

Colistin penetration into the cerebrospinal fluid (CSF) was studied in five critically ill adult patients receiving colistin methanesulfonate for infections by multiresistant gram-negative bacilli. Colistin concentrations were determined in paired serum and CSF samples, with the latter taken by lumbar puncture, with the exception of one patient with an external ventriculostomy. CSF-to-serum ratios (0.051 to 0.057) for all study patients coincided at all sampling times. The low level (5%) of penetration suggests inadequate bactericidal colistin concentrations in the CSF.

Approach to patients with pulmonary embolism in a surgical intensive care unit.

BACKGROUND/AIMS: Pulmonary embolism (PE) is a potentially life threatening disease. Clinical signs and symptoms allow the clinician to determine the pretest probability of someone having pulmonary embolism but are insufficient to diagnose or rule out the condition. This paper aims to study the clinical presentation, identify the risk factors and evaluate the diagnostic strategies and management of patients with PE. METHODOLOGY: The medical files of 69 patients were searched, who were diagnosed with PE and who were admitted to the Surgical Care Unit. RESULTS: Dyspnea, pleuritic pain, haemoptysis, fever and cough were the most common presenting symptoms. Risk factors for PE were found in 90% of cases. D-dimers assay was elevated in all cases (100%) and the other diagnostic strategies used showed great accuracy in confirming the pretest probabilities of PE. It is of high importance that 75% of the patients had deep vein thrombosis as assessed by venous ultrasonography. Mortality due to PE was approximately 6.9%. CONCLUSIONS: PE can be often overlooked with hazardous consequences. Clinical evaluation in combination with spiral CT or lung scintigraphy and vein ultrasound and D-dimer level can establish the diagnosis in the majority of patients so that effective treatment to be started as soon as possible.

Effect of different ventilatory strategies on local and systemic cytokine production in intact swine lungs in vivo.

The purpose of the study was to investigate the effect of different ventilatory strategies on local and systemic cytokine production in swine with intact lungs in vivo after 4 h of mechanical ventilation. Twenty-five swine were anesthetized and then randomized into five groups (n = 5): (1) low tidal volume zero PEEP (LVZP); (2) medium tidal volume zero PEEP (MVZP); (3) high tidal volume zero PEEP (HVZP); (4) low tidal volume PEEP (LVP); (4) high tidal volume PEEP (HVP). Respiratory rate was adjusted to maintain normocapnia and fraction of inspired oxygen (FiO2) was 1.0. TNF-alpha and IL-10 were measured in BALF and serum at baseline, 2 h, and 4 h of MV. One animal in LVZP (2 h) and two in HVP (3 h) group died before the end of the experiment. TNF-alpha level in BALF was significantly higher in LVZP and LVP at 4 h compared to baseline and the other groups. IL-10 level in BALF was significantly higher in LVP at 4h compared to baseline and the other groups. There was a statistically significant increase in serum TNF-alpha levels at 4 h in LVP group compared to baseline and the other groups at 4 h. There was statistically significant increase in serum IL-10 levels in HVZP and LVP groups at 2 and 4 h which was significantly higher compared to the other groups at 4 h. Our results show that a) low volume MV may induce local and systemic pro- and anti-inflammatory cytokine increase b) in the presence of pro-inflammatory cytokine response there is also an anti-inflammatory response in the same compartment (lungs, circulation). c) There maybe loss of alveolar-to-systemic cytokine compartmentalization.

The influence of varying blood and dialysate flow on haemodialysis adequacy.

The aim of this study was the exploration and correlation of the influence of variations in blood flow and dialysate flow on haemodialysis adequacy through the quantitative indexes Kt/V, TACurea and PCR. A prospective study of 48 patients subjected to haemodialysis was carried out. The collection of data included taking blood and urine samples according to the directives of DOQI, for a total of 8 months. Statistical analysis was based on the paired t-test and multiple regression analysis. The variations in blood flow and dialysate flow are positively related to the variation of the indexes Kt/V, TACurea and PCR and consequently to the haemodialysis adequacy both as isolated factors and when combined together.

Total antioxidant status and severity of community-acquired pneumonia: are they correlated?

BACKGROUND: Oxidant/antioxidant imbalance has been reported in various respiratory diseases including pneumonia. However, the role of blood antioxidants has not been fully discussed. OBJECTIVES: The aim of this exploratory study was to assess serum total antioxidant status (TAS) in patients with community-acquired pneumonia (CAP) and the probable correlation with the severity of the disease. METHODS: Thirty patients (22 men, 8 women; mean age of 48 +/- 21 years) and 10 healthy nonsmokers (mean age 44 +/- 16 years) were studied. Clinical, laboratory and radiological findings were recorded on the day of admission and on the 7th day. A severity score was calculated using the Fine scale. Serum TAS was measured at the same time points using a colorimetric method. RESULTS: On admission, TAS (TAS1) was significantly lower than on the 7th day (TAS2) (0.84 +/- 0.13 mmo/l vs. 1.00 +/- 0.17 mmo/l; p = 0.0001) and compared with the healthy subjects (0.84 +/- 0.13 vs. 1.19 +/- 0.09 mmol/l; p < 0.001). TAS change (TAS2 - TAS1) was statistically significantly more marked in smokers (0.17 vs. 0.28, p = 0.001), in patients with factors predisposing to CAP (0.12 vs. 0.37; p = 0.000) and in patients with gram-negative pneumonia (0.16 vs. 0.35; p = 0.000). On the other hand, change in TAS was statistically significantly less marked in patients with lobar pneumonia (0.27 vs. 0.17; p = 0.001). Additionally, TAS change was positively correlated to white blood count on admission (r = 0.39; p = 0.029). CONCLUSIONS: It is concluded that serum TAS is decreased in patients with CAP, suggesting the presence of oxidative stress, and that change in TAS seems to be influenced by disease severity. TAS measurement may be useful in estimating the severity of CAP and is a probable indication for the administration of antioxidants in the management of the disease.

Venous pressure measurements in the superior and inferior vena cava: the influence of intra-abdominal pressure.

BACKGROUND/AIMS: To investigate the relationship of pressure in the inferior vena cava (Pivc) with a) pressure in the superior vena cava (Psvc), b) intra-abdominal pressure as measured in the urinary bladder (Pcyst). METHODOLOGY: A prospective study of 38 mechanically ventilated patients. Simultaneous measurements of Psvc, Pivc and Pcyst (151 sets of measurements) were performed. Measurements were divided in: Group A (Pcyst < 10 mmHg), group B (10 mmHg < or = Pcyst < 15 mmHg), group C (Pcyst > or = 15 mmHg). Statistical analysis was performed with paired t-test, Pearson correlation. Results are expressed in mean +/- SEM. RESULTS: In Groups A and B, Psvc and Pivc were not significantly different and they were highly correlated (10.8+/-0.5 mmHg vs. 10.9+/-0.5 mmHg, r=0.93 for Group A and 14.4+/-0.7 mmHg vs. 14.7+/-0.6 mmHg, r=0.87 for Group B). Pcyst was significantly lower than Pivc in both groups. In Group C, Pivc was significantly higher than Psvc (18.9+/-0.7 mmHg vs. 16.4+/-0.7 mmHg). There was no significant difference between Pivc and Pcyst (19.2+/-0.6 mmHg). Pivc significantly correlated with Pcyst (r=0.78) and Psvc (r=0.7). A. When Pcyst > Psvc, Pivc was higher than Psvc (p<0.01). With Pcyst < 15 mmHg, no significant difference was found between Pcyst and Pivc and they were correlated (r=0.766, p<0.05). Pressures in the superior and inferior vena cava were also correlated (r=0.764, p<0.05). With Pcyst > or = 15 mmHg, Pivc was lower than Pcyst (p<0.01). It correlated highly with Pcyst (r=0.85, p<0.01) and less strongly with Psvc (r=0.701, p<0.01). B. When Pcyst < or = Psvc, no difference between Pivc and Psvc was observed. With Pcyst < 15 mmHg, Pivc was higher than Pcyst (p<0.01) and highly correlated with Psvc (r=0.932, p<0.01). Pivc also correlated with Pcyst (r=0.69, p<0.01). With Pcyst > or = 15 mmHg, Pivc was higher than Pcyst (p<0.01) and correlated with Psvc (r=0.74, p<0.01) and Pcyst (r=0.789, p<0.01). CONCLUSIONS: Although Psvc and Pivc are interchangeable in the absence of an increased Pcyst, when Pcyst is high, measurements of Pivc are misleading. A Pcyst > Psvc results in a "waterfall" effect, and Pivc does not accurately reflect Psvc any more.

Temperature and serum proinflammatory cytokine changes in patients with NSCLC after BAL.

We examined the effects of bronchoalveolar lavage (BAL) and BAL fluid characteristics on the systemic proinflammatory cytokine expression and their relation to clinical and laboratory findings. Thirty patients suspected to have lung cancer were subjected to fiber-optic bronchoscopy (FOB) and BAL. Clinical and laboratory findings were determined at baseline, 4 h, and 24 h, including lung auscultation, temperature, chest X-ray, WBC, neutrophils, and serum IL-1beta, IL-6, and TNF-alpha. BAL fluid characteristics were determined including cytokine levels. Fifteen volunteers served as controls to determine serum variation of the same cytokines. Significant temperature elevation was defined as 1 degrees C increase compared to baseline. BAL was associated with temperature and serum TNF-alpha and IL-6 but not IL-1beta increase at 4 h. Four patients (13.3%) developed temperature over 38 degrees C. In controls there were no significant changes between baseline and 24 h measurements for the same cytokines. Eleven patients (36.6%) developed a significant temperature elevation 4 h after BAL. These patients had a statistically significant ( p < 0.05) increase in serum IL-6 at 4 h and in TNF-alpha at both 4 and 24 h after BAL compared with the nonsignificant temperature increase group. BAL characteristics were not different between the two groups. On the other hand, BAL fluid IL-6 and TNF-alpha levels were significantly higher ( p < 0.05) in the nonfever group. Significant temperature increase was observed in 36.6% of the patients undergoing BAL and associated with significant serum TNF-alpha and IL-6 increase at 4 h. Lung cytokines levels, alveolar macrophages, and BAL fluid characteristics are not related to temperature and serum proinflammatory cytokine increase. The hypothesis of alveolar macrophages derive from cytokine production and shift to the systemic circulation cannot be supported by our data.

Effect of polarized light in the healing process of pressure ulcers.

A trial was conducted to examine the effect of polarized light on pressure ulcers of 1st, 2nd and 3rd grades. Patients with two pressure ulcers, one of which received the polarized light therapy (experimental ulcer) and the other acting as control, were included in the study. The experimental ulcers received treatments for 2 weeks consisting a 5 min therapy session each day, excluding weekends, for 10 days. Experimental and control ulcers were assessed as they appeared on admission and reassessed at the end of each week. Fifty-five patients aged 37-85 years (67.1 +/- 11.9 years) were studied. Pressure ulcers of 1st, 2nd and 3rd grades receiving extra treatment with polarized light had increased values of epithelial tissue between the first and second assessments of 0-30.9% and between the second and third assessments of 30.9-21.7%. Values of the control pressure ulcers were, respectively, from 0 to 5.5% and from 5.5% to 3.1%. The mean pink/white colour values of the experimental ulcers, between the first and second measurements increased significantly compared with the control ulcers (P = 0.021) and also increased significantly between the second and third measurements (P = 0.003). The mean values of 'no and minimal exudate' of the experimental ulcers increased significantly between first and second measurements compared with the control ulcers (P = 0.001), and similarly, significantly between the second and third measurements (P = 0.002). Mean surface areas of the experimental ulcers decreased significantly between the first and second measurements from 2.84 to 2.54 cm2 (P < or = 0.001) and between the first and third measurements from 2.84 to 2.26 cm2 (P < or = 0.001). Mean surface areas of the control ulcers decreased between the first and second measurements from 2.10 to 2.08 cm2 (P < or = 0.42) and between the first and third measurements from 2.10 to 2.04 cm2 (P < or = 0.007). Pressure ulcers subjected to extra treatment with polarized light in the early stages (first to third measurements) showed improvement in the healing process than the control ulcers.