Key Messages for a Frailty Prevention and Management Policy in Europe from the ADVANTAGE JOINT ACTION Consortium.

In the 2015 Ageing Report, the European Commission (EC) and the Economic Policy Committee stated that coping with the challenge posed by an ageing population will require determined policy action in Europe, particularly in reforming pension, health care and long-term care systems. The concern for this situation motivated the EC, the Parliament and many of the Member States (MS) to co-fund, in the 2015 call of the Third European Health Programme of the European Union 2014-2020, the first Joint Action (JA) on the prevention of frailty. ADVANTAGE JA brings together 33 partners from 22 MSs for 3 years. It aims to build a common understanding on frailty to be used in the MSs by policy makers and other stakeholders involved in the management, both at individual and population level, of older people who are frail or at risk for developing frailty throughout the European Union (EU). It is a formidable challenge but also a great opportunity for concerted action resulting in fostering effective and successful policies in frailty prevention and management in the participating MS. The Consortium has 2 years of hard work ahead to contribute to the needed change for frailty related disability free Europe. The first practical step towards this aim was the preparation of a document: the State of the Art on Frailty Report to support an overview of evidence of what works and what does not work on frailty prevention and management. Subsequently, this will be reflected in the advice that the JA will give to policy makers at MS level. Overall, these messages intend to be an instrument of added value to advocate for policy driven decisions on frailty prevention and management in the JA participating MSs and subsequently towards a frailty related disability free older population in Europe. The aim of this paper is to describe ADVANTAGE JA general structure, approach and recommendations towards a European health and social policy which will support frailty prevention in the participating MS.

Health-related quality of life of a very special population: monks of Holy Mountain Athos, Greece.

PURPOSE: The investigation of Health-Related Quality of Life (HRQOL) of Orthodox Christian monks who live at the Holy Mount Athos in Greece, and its correlation with demographic characteristics and Sense of Coherence (SOC-13). METHODS: A cross-sectional study was designed. The seven monasteries and five scetes with the largest number of monk population were invited to participate. Two monasteries and 1 scete gave their permission for the study. The final monks sample was formed by 166 monks from 215 who participated to the study. HRQOL was assessed using the SF-12 and Sense of Coherence the SOC-13 scales that were completed by monks from May to August 2012. Μultiple linear regression analyses were conducted to explore the association of the HRQOL subscales with the demographics and SOC-13. RESULTS: The mean age was 45.5 ± 13.0 years; 83.7% lived in communal monasteries, and the mean number of years in monasticism was 18.4 ± 12.1. The mean value of their Physical Component Summary (PCS) score was 47.3 ± 5.3, which is lower than in the general Greek men population, while their Mental Component Summary (MCS) score was 56.4 ± 5.8, which is higher than in the general Greek men population. The mean value of SOC-13 was 65.7 ± 6.5. Positive association for PCS appeared for place of living (ß = 5.43, SE = 1.27, p < 0.001) and negative association for age (ß = -0.16, SE = 0.03, p < 0.001) while for MCS for number of years in monasticism (ß = 0.07, SE = 0.06, p = 0.023) and sense of coherence (ß = 0.47, SE = 0.06, p < 0.001). CONCLUSIONS: The results indicated that monks had better mental health but worse physical health compared to the general Greek male population. More studies are required to validate the above findings.

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.

Increase of circulating endocan over sepsis follow-up is associated with progression into organ dysfunction.

How circulating inflammatory mediators change upon sepsis progression has not been studied. We studied the follow-up changes of circulating vasoactive peptides and cytokines until the improvement or the worsening of a patient and progression into specific organ dysfunctions. In a prospective study, concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan and angiopoietin-2 (Ang-2) were measured in serum by an enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h upon progression into new organ dysfunction (n = 141) or improvement (n = 34). Endocan and Ang-2 were the only parameters that were significantly increased among patients who worsened. Any increase of endocan was associated with worsening with odds ratio 16.65 (p < 0.0001). This increase was independently associated with progression into acute respiratory distress syndrome (ARDS) as shown after logistic regression analysis (odds ratio 2.91, p: 0.002). Changes of circulating cytokines do not mediate worsening of the critically ill patients. Instead endocan and Ang2 are increased and this may be interpreted as a key-playing role in the pathogenesis of ARDS and septic shock. Any increase of endocan is a surrogate of worsening of the clinical course.

Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

OBJECTIVES: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. METHODS: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. RESULTS: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). CONCLUSIONS: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment.

Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.

Sense of coherence in people with and without type 2 diabetes mellitus: an observational study from Greece.

Background Antonovsky's concept of sense of coherence (SOC) has been suggested to relate to health, especially mental health and preventive health behaviours. Psychological distress has been identified as a risk factor for pre-diabetes and type 2 diabetes mellitus. The study of SOC and diabetes has not received much attention in Greece. This study aims to explore the extent to which type 2 diabetes mellitus can affect the SOC score. Methods An observational design was used to test the study hypothesis that individuals with type 2 diabetes mellitus would have a lower SOC than those without diabetes mellitus. A total of 202 individuals were studied, consisting of 100 people with diabetes mellitus (the study group) and 102 people with non-chronic orthopaedic conditions (the control group). All of the participants were patients of the Diabetic Clinic or the Orthopaedic Clinic of Livadia Hospital in Central Greece. SOC was assessed using a 29-item SOC questionnaire that had been translated into Greek and validated. Results Patients without type 2 diabetes mellitus had 2.4 times higher odds of having a high SOC score than patients with type 2 diabetes mellitus (P = 0.036; odds ratio [OR] = 2.35, 95% confidence interval [CI] = 1.06-5.23). Male patients had 3.9 times higher odds of having a high SOC score (P < 0.001; OR = 3.85, 95% CI = 1.71-8.67) than female patients. With regard to education, patients with a lower level of education had almost three times higher odds of having a high SOC score than patients with a higher level of education (P = 0.024; OR = 2.97, 95% CI = 1.15-7.67). Conclusions This study adds to the existing literature and indicates that SOC is a health asset. A study with an experimental design would clarify the interesting hypothesis of this study.

Wernicke's encephalopathy and anabolic steroid drug abuse. Is there any possible relation?

Wernicke's encephalopathy is a reversible, neurologic disorder due to thiamine deficiency which is mainly related to chronic alcohol abuse. We report a case of a young male patient, who was bodybuilder and anabolic drug user, in whom encephalopathy was diagnosed after a short medical course in the ICU after a major upper gastrointestinal bleeding (Mallory-Weiss syndrome) and hypovolemic shock. His clinical condition was typical for Wernicke's encephalopathy and although neuroimaging tests were not indicative, the patient received thiamine supplement therapy, which resulted in rapid clinical improvement. The diagnosis was based only on clinical sings and anabolic drug abuse was considered as a possible predisposing factor for the manifestation of the syndrome.

Hospital outbreak caused by Klebsiella pneumoniae producing KPC-2 beta-lactamase resistant to colistin.

We describe a hospital outbreak caused by colistin-resistant Klebsiella pneumoniae producing KPC-2 beta-lactamase in two distinct medical centres. Seven clinical isolates of K. pneumoniae exhibiting resistance to carbapenems were collected from patients with hospital-acquired infection. All isolates were phenotypically positive for carbapenemase activity but negative for metallo-beta-lactamase production. PCR analysis using specific primers for bla(KPC), bla(SHV), bla(TEM) and bla(CTX-M) demonstrated that all clinical strains of K. pneumoniae from hospital A and one isolate from hospital B were genetically related and carried bla(KPC-2) in addition to bla(SHV-12). In contrast, the remaining isolate carried bla(S)(HV-5) with bla(K)(PC-2) and yielded a different profile. These results indicate the clonal spread of KPC producers between hospitals as well as the acquisition of KPC genes by different K. pneumoniae strains. All isolates were resistant to carbapenems, beta-lactams, ciprofloxacin, aminoglycosides and colistin, but intermediately susceptible to tigecycline and susceptible to gentamicin. The infection was fatal in five cases. The emergence of colistin-resistant K. pneumoniae possessing bla(KPC)(-2) underscores the implementation of strict control measures to prevent their dissemination of these organisms in hospitals.

Alterations in carbon dioxide release during abdominal aortic clamping for aneurysmal or occlusive repair.

BACKGROUND: Application and removal of an infrarenal aortic clamp is associated with changes in oxygen consumption, especially when collateral perfusion is limited. Carbon dioxide production during abdominal aortic clamping is expected also to change. The aim of this study was to evaluate the alterations of CO2 release during abdominal aortic surgery. DESIGN: prospective study. SETTING: University Hospital, Greece. PATIENTS: 17 patients undergoing abdominal aortic aneurismal (AAA) repair and 8 patients undergoing repair of aortoiliac occlusive disease. INTERVENTION: intraoperative record or calculation of PaCO2, PetCO2, PECO2, VD, VDalv, and VCO2. Patients with aneurysms were randomly divided to have constant ventilation (group AA) or modified ventilation to preserve normocapnia (group AB) during clamping. Ventilation was kept constant in the occlusive patients group (group OD). RESULTS: Patients with AAA showed a significant decrease of VCO2 during clamping and an elevation after unclamping in both groups (AA and AB), with no difference of statistical importance between them. During clamping, PetCO2/ PaCO2 ratio was decreased and VDalv was increased especially in group AA, while unclamping produced the opposite effect. Occlusive patients showed insignificant alterations. CONCLUSIONS: Our results suggest that, the calculated alveolar dead space is only an indicator of the true V/Q in patients with AAA, because it is strongly dependent on the CO2 load to the lungs, which is markedly altered in the same period. The modification of ventilation during clamping based only on PetCO2 and not on arterial sampling, could possibly lead to hypercarbia in these patients.