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Purpose: Adherence to treatment can be defined as the degree to which a patient’s behavior is consonant with medical or health advice he or she receive as part of his treatment regimen. The aim of this study was: 1) to measure the rate of treatment adherence to among patients with lung cancer from the prospect of both patients and physicians, 2) to measure the degree of concordance between the two prospect, and 3) to identify factors related to adherence for both prospect (patients and physicians). Materials and Methods: A total of 250 patients were included in this study. Information about socio-economic characteristics, depressive and anxiety symptoms (Hospital Anxiety and Depression scale), nicotine dependence (Fagerstrom scale), barriers to accessing care, and the level of treatment adherence was collected through interview. Physicians were enquired about disease and treatment variables as well as patients’ level of adherence. Results: From the patient perspective, only 1.2% of patients displayed poor adherence; whereas the corresponding percentage among physicians was 12.4%. The concordance between the two was low: 0.244. The correlation of measurements made on the same individual was found to be equal to 0.14. Barriers to accessing medication (O.R.=2.82, 95% C.I.: 1.01-8.09) was the only risk factor when adherence was self-rated; barriers to accessing medication (O.R.=2.45, 95% C.I.: 1.03-5.86), education equal to 12 years (O.R.=0.33, 95% C.I.: 0.13-0.82) or higher than 12 years (O.R.=0.28, 95% C.I.: 0.08-0.96), nicotine dependence (O.R.=1.41, 95% C.I. 1.17-1.69) and HADS anxiety score (O.R.=1.15, 95% C.I. 1.03-1.30) were the predictors in physicians’ rating. Conclusions: Differences in rating adherence may underpin communication gaps between patients and physicians. Systemic determinants of poor adherence should not be overlooked. A concerted effort by researchers, physicians and policy makers in defining as well as communicating adherence, while removing its barriers should be made.

ΣΚΟΠΟΣ:Ο TREM-1 (triggering receptor expressed on myeloid cells), ένας υποδοχέας που εκφράζεται στα ουδετερόφιλα και τα μονοκύτταρα, υπερεκφράζεται στη σήψη και φαίνεται ότι παίζει έναρόλο-κλειδί για τη ρύθμιση της φλεγμονώδους απόκρισης. Μελετήσαμε την γονιδιακή και επιφανειακή έκφραση του TREM-1 σε σχέση με την τελική έκβαση. ΜΕΘΟΔΟΙ: Δείγματα περιφερικού φλεβικού αίματος ελήφθησαν από 75 σηπτικούς ασθενείς (41 ασθενείς με σήψη, 25 με σοβαρή σήψη και 9 με σηπτική καταπληξία) εντός είκοσι τεσσάρων ωρών μετά την εισαγωγή τους στη μελέτη και στη συνέχεια κατά την τρίτη και έβδομη μέρα νοσηλείας. Η επιφανειακή έκφραση του TREM-1 επί των μονοκυττάρων εκτιμήθηκε με κυτταρομετρία ροής. Η γονιδιακή έκφραση του TREM-1 στα κυκλοφορούντα μονοκύτταρα αξιολογήθηκε με RT-PCR. Επιπλέον προσδιορίστηκε η συγκέντρωση του sTREM-1 η οποία προσδιορίστηκε στον ορό με μία ανοσοενζυμική μέθοδο. ΑΠΟΤΕΛΕΣΜΑΤΑ: Παρόλο που η επιφανειακή και η γονιδιακή έκφραση του TREM-1, καθώς και η συγκέντρωση του sTREM-1 δεν διέφεραν μεταξύ σήψης, σοβαρής σήψης και σηπτικής καταπληξίας την ημέρα 1, οι επιζώντες είχαν μεγαλύτερη έκφραση στην επιφάνεια TREM-1 στις ημέρες 3 και 7 σε σύγκριση με μη επιζώντες. Η συγκέντρωση του sTREM-1 στους μη επιζώντες μειώθηκε την ημέρα 3 σε σύγκριση με την αρχική τιμή της. Οι ασθενείς με την αύξηση της γονιδιακής έκφρασης του TREM-1 στα μονοκύτταρα από την ημέρα 1 έως την ημέρα 3 είχαν παρατεταμένη επιβίωση σε σύγκριση με ασθενείς με μείωση της έκφρασης του γονιδίου τουTREM-1 από την ημέρα 1 έως την ημέρα 3 (p: 0,031). ΣΥΜΠΕΡΑΣΜΑΤΑ: Η πρώιμη μείωση της έκφρασης του γονιδίου της TREM-1 στα μονοκύτταρα σχετίζεται με κακή έκβαση. Το φαινόμενο αυτό μπορεί να οφείλεται στην ανοσοκαταστολή που προκαλείται από το σηπτικό επεισόδιο μέσω μείωσης του προ-φλεγμονώδους υποδοχέα επιφανείας TREM-1.

Introduction: Lung cancer exerts a significant societal and health-care–related economic burden and chemotherapy drugs constitute a major factor of total direct cost. The aim of the present study was to assess the direct health-care cost of lung cancer in Greece by conducting a retrospective analysis on the last 6 months of life. Methods: The present study was based on both the medical data and costs of treatment of deceased adult patients who suffered from terminal stage IIIB/IV lung cancer (non-small cell lung cancer and small cell lung cancer) during the last 6 months of their life. The study’s protocol was approved by the Hospital’s Research Ethics Committee. Costs included outpatient (outpatient services) and inpatient (inpatient services) costs. Descriptive statistics were mainly used for statistical analysis. Results: The files of 144 patients were analyzed. The total cost of health-care services for the study population during the last 6 months of life was attributed by 57% to inpatient services, whereas chemotherapy costs (74%) comprised the largest proportion of the total inpatient cost. The highest expenditure for outpatient services was attributed to concomitant medication (59%), followed by the cost of tests (21%) and radiotherapy (20%). Conclusions: The results of our study indicate that both inpatient and outpatient costs were substantial. The main inpatient and outpatient cost drivers were chemotherapy and concomitant medication, respectively. A more comprehensive nationwide study would be useful to validate our results and to include also indirect costs of cancer care in Greece.

OBJECTIVES Currently used biomarkers insufficiently discriminate between patients with systemic inflammatory response syndrome of non-infectious origin and sepsis. The aim of this study was to identify surrogate markers that distinguish between systemic inflammatory response syndrome and sepsis as well as the underlying type of infection by targeted metabolomics. DESIGN Retrospective analysis. SETTINGS Six sites of the Hellenic Sepsis Study Group and at Jena University Hospital. PATIENTS A total of 406 patients were analyzed: 66 fulfilling criteria for diagnosis of systemic inflammatory response syndrome, 100 for community-acquired pneumonia, 112 for urinary tract infection, 83 for intra-abdominal infection and 45 for bloodstream infection. Patients were divided into test cohort (n = 268) and confirmation cohort (n = 138). INTERVENTIONS A total of 186 metabolites were determined by liquid chromatography tandem mass spectrometry. MEASUREMENTS AND MAIN RESULTS Serum concentrations of most acylcarnitines, glycerophospholipids and sphingolipids were altered in sepsis compared to systemic inflammatory response syndrome. A regression model combining the sphingolipid SM C22:3 and the glycerophospholipid lysoPCaC24:0 was discovered for sepsis diagnosis with a sensitivity of 84.1% and specificity of 85.7%. Furthermore, specific metabolites could be used for the discrimination of different types of infection. The glycerophospholipid lysoPCaC26:1 identified patients with community-acquired pneumonia in sepsis or severe sepsis/septic shock. Within severe sepsis/septic shock, patients with bloodstream infection could be discriminated by a decrease of acetylornithine. Changes of metabolites between sepsis and severe sepsis/septic shock also varied according to the underlying type of infection, showing that putrescine, lysoPCaC18:0 and SM C16:1 are associated with unfavorable outcome in community-acquired pneumonia, intra-abdominal infections and bloodstream infections, respectively. CONCLUSIONS Using a metabolomics approach, single metabolites are identified that allow a good, albeit at about 14% false positive rate of sepsis diagnosis. Additionally, metabolites might be also useful for differentiation and prognosis according to the type of underlying infection. However, confirmation of the findings in ongoing studies is mandatory before they can be applied in the development of novel diagnostic tools for the management of sepsis.

Objective. To assess the effects of an 8-week stress management and health promotion program on women undergoing breast cancer chemotherapy treatment. Patients and methods. A total of 61 patients were recruited in 2 cancer centers and were randomly assigned to the intervention program (n = 30) or control group (n = 31). The intervention program consisted of different stress management techniques, which were combined with instructions for lifestyle modification. Assessments were carried out through questionnaires and measurement of body mass index (BMI) at baseline and at the end of the 8-week program. Results. In all, 25 participants completed the intervention program, whereas 28 participants completed the observational control program. The intervention program resulted in a small effect size on internal dimension of Health Locus of Control (HLC) and a medium effect size on stress, depression, anxiety, night sleep duration, and chance dimension of HLC. A strong effect size was recorded for BMI and sleep onset latency. Self-rated health, spiritual well-being, and powerful others dimension of HLC were not significantly affected. Additionally, some of the participants reported a reduction in the side effects caused by chemotherapy. Conclusions. The intervention resulted in several benefits for the general health status of patients. Therefore, it should be considered as feasible and potentially beneficial for women undergoing breast cancer chemotherapy. However, it is necessary for this intervention to be tested through a randomized controlled trial in a larger sample of patients before adopting this program in standard cancer care.

One prospective, open-label, non-randomized study was conducted in 100 patients to define the antipyretic and analgesic effect of a new intravenous formulation of 1 g of paracetamol; 71 received paracetamol for the management of fever and 29 received paracetamol for pain relief after abdominal surgery or for neoplastic pain. Serial follow-up measurements of core temperature and of pain intensity were done for 6 h. Additional rescue medications were recorded for 5 days. Blood was sampled for the measurement of free paracetamol (APAP) and of glucuronide-APAP and N-sulfate-APAP by an HPLC assay. Defervescence, defined as core temperature below or equal to 37.1°C, was achieved in 52 patients (73.2%) within a median time of 3 h. Patients failing to become afebrile with the first dose of paracetamol became afebrile when administered other agents as rescue medications. Analgesia was achieved in 25 patients (86.4%) within a median time of 2 h. Serum levels of glucuronide-APAP were greater among non-responders to paracetamol. The presented results suggest that the intravenous formulation of paracetamol is clinically effective depending on drug metabolism. Keywords:: intravenous paracetamol, fever, pain, analgesia

Background A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis. Methods Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes. Results The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502). Conclusions Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.

Background Current knowledge on the exact ligand causing expression of TREM-1 on neutrophils and monocytes is limited. The present study aimed at the role of underlying infection and of the causative pathogen in the expression of TREM-1 in sepsis. Methods Peripheral venous blood was sampled from 125 patients with sepsis and 88 with severe sepsis/septic shock. The causative pathogen was isolated in 91 patients. Patients were suffering from acute pyelonephritis, community-acquired pneumonia (CAP), intra-abdominal infections (IAIs), primary bacteremia and ventilator-associated pneumonia or hospital-acquired pneumonia (VAP/HAP). Blood monocytes and neutrophils were isolated. Flow cytometry was used to estimate the TREM-1 expression from septic patients. Results Within patients bearing intrabdominal infections, expression of TREM-1 was significantly lower on neutrophils and on monocytes at severe sepsis/shock than at sepsis. That was also the case for severe sepsis/shock developed in the field of VAP/HAP. Among patients who suffered infections by Gram-negative community-acquired pathogens or among patients who suffered polymicrobial infections, expression of TREM-1 on monocytes was significantly lower at the stage of severe sepsis/shock than at the stage of sepsis. Conclusions Decrease of the expression of TREM-1 on the membrane of monocytes and neutrophils upon transition from sepsis to severe sepsis/septic shock depends on the underlying type of infection and the causative pathogen.

A recent randomized trial of our group showed that blind treatment with clarithromycin decreased mortality from septic shock and multiple organ dysfunction, shortened time until resolution of infection in patients with severe sepsis/shock and decreased hospitalization costs [1]. The efficacy of clarithromycin in relation with the type of failing organs is analyzed.

Introduction Although major changes of the immune system have been described in sepsis, it has never been studied whether these may differ in relation to the type of underlying infection or not. This was studied for the first time. Methods The statuses of the innate and adaptive immune systems were prospectively compared in 505 patients. Whole blood was sampled within less than 24 hours of advent of sepsis; white blood cells were stained with monoclonal antibodies and analyzed though a flow cytometer. Results Expression of HLA-DR was significantly decreased among patients with severe sepsis/shock due to acute pyelonephritis and intraabdominal infections compared with sepsis. The rate of apoptosis of natural killer (NK) cells differed significantly among patients with severe sepsis/shock due to ventilator-associated pneumonia (VAP) and hospital-acquired pneumonia (HAP) compared with sepsis. The rate of apoptosis of NKT cells differed significantly among patients with severe sepsis/shock due to acute pyelonephritis, primary bacteremia and VAP/HAP compared with sepsis. Regarding adaptive immunity, absolute counts of CD4-lymphocytes were significantly decreased among patients with severe sepsis/shock due to community-acquired pneumonia (CAP) and intraabdominal infections compared with sepsis. Absolute counts of B-lymphocytes were significantly decreased among patients with severe sepsis/shock due to CAP compared with sepsis. Conclusions Major differences of the early statuses of the innate and adaptive immune systems exist between sepsis and severe sepsis/shock in relation to the underlying type of infection. These results may have a major impact on therapeutics.

A considerable body of evidence indicates the contribution of the immune system to the mechanisms leading to acute pancreatitis [1]. Data focusing on the early course of events at the clinical ground of the process are lacking. The aim of the present study was to provide a complex evaluation of peripheral blood monocyte and subpopulations of lymphocytes in patients with acute pancreatitis and systemic inflammatory response syndrome.

Background TREM-1 (triggering receptor expressed on myeloid cells), a receptor expressed on neutrophils and monocytes, is upregulated in sepsis and seems to tune the inflammatory response. We explored the expression of TREM-1 at the gene level and on cell membranes of monocytes and association with clinical outcome. Methods Peripheral venous blood was sampled from 75 septic patients (39 patients with sepsis, 25 with severe sepsis and 11 with septic shock) on sepsis days 1, 3 and 7. TREM-1 on monocytes was measured by flow cytometry; gene expression of TREM-1 in circulating mononuclear cells was assessed by real-time PCR. sTREM-1 was measured in serum by an enzyme immunoassay. Results Although surface TREM-1, sTREM-1 and TREM-1 gene expression did not differ between sepsis, severe sepsis and septic shock on day 1, survivors had greater expression of surface TREM-1 on days 3 and 7 compared to non-survivors. sTREM-1 on non-survivors decreased on day 3 compared to baseline. Patients with increase of monocyte gene expression of TREM-1 from day 1 to day 3 had prolonged survival compared to patients with decrease of gene expression of TREM-1 from day 1 to day 3 (p: 0.031). Conclusions Early decrease of gene expression of TREM-1 in monocytes is associated with poor outcome. A reciprocal decrease of the pro-inflammatory surface receptor TREM-1 linked with sepsis-induced immunosuppression may be part of the explanation. Electronic supplementary material The online version of this article (doi:10.1186/s12865-014-0063-y) contains supplementary material, which is available to authorized users.

Introduction Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. Methods A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. Results Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥17 and suPAR ≥12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II