European strategy for vaccine development against infectious diseases.

Immunisation efforts save millions of lives every year, but vaccines hold the potential to deliver even greater health benefits for mankind. Vaccine research and development is highly complex, and it requires concerted public funding efforts to support. In this paper we discuss EU funding priorities and the resulting recent advancements in European vaccine research, and we lay out the EU strategy for aiding promising vaccine candidates to successfully reach the market.

Defining the needs of ICU patient families in a suburban/rural Greek population: a prospective cohort study.

AIM: To define the needs of intensive care unit patients' families in the specific suburban/rural population of Crete Island. BACKGROUND: Families of intensive care unit patients have specific needs that should also be addressed by the intensive care unit-care team. Current research has mostly concentrated on families from an urban setting, therefore may not be applicable to other populations. DESIGN: Prospective cohort study. METHODS: Family members of patients admitted in the intensive care unit for ≥ 48 hours over 18 months, in a mixed medical-surgical, 11 bed closed intensive care unit. Questionnaire: The Greek translation of Critical Care Family Need Inventory, which consists of 45 need items covering the information, reassurance, proximity, support and comfort domains. Each item was scored on a four-point scale (1 = very important to 4 = not important). Participants were also asked to single out the most important need from the Critical Care Family Need Inventory and complete a questionnaire on basic demographic characteristics. RESULTS: Two hundred and thirty (65%) family members completed the questionnaire. Mean score for each of the 45 items ranged from 1.03-3 (scale from 1: very important-4: not important). Fourteen items were rated by responders as very important (mean score <1.25). Reassurance need items were consistently singled out as most important regardless of the participant's background. Participants with a lower educational and socio-economical status rated support need items as more important than those with a higher status. CONCLUSION: In this particular suburban/rural population, both 'universal' reassurance needs and specific support needs related to responders' educational or socio-economical background were identified. RELEVANCE TO CLINICAL PRACTICE: Enhanced recognition of these needs may improve quality of care offered by intensive care unit-care team to families of their patients.

Effect of propofol on breathing stability in adult ICU patients with brain damage.

The aim of the study was to investigate Propofol's effect on breathing stability in brain damage patients, as quantified by the Loop Gain (LG) of the respiratory system (breathing stability increases with decreasing LG). In 11 stable brain damage patients full polysomnography was performed before, during and after propofol sedation, titrated to achieve stage 2 or slow wave sleep. During each period, patients were ventilated with proportional assist ventilation and the % assist was increased in steps, until either periodic breathing (PB) occurred or the highest assist (95%) was achieved. The tidal volume amplification factor (VT(AF)) at the highest assist level reached just before PB occurred was used to calculate LG (LG=1/VT(AF)). In all but one patient, PB was observed. With propofol, the assist level at which PB occurred (73 + or - 19%) was significantly higher, than that before (43 + or - 35%) and after propofol sedation (49 + or - 29%). As a result, with propofol LG (0.49 + or - 0.2) was significantly lower than that before (0.74 + or - 0.2) and after propofol sedation (0.69 + or - 0.2) (p<0.05). We conclude that Propofol decreases LG. Therefore it exerts an overall stabilizing effect on control of breathing.

Is proportional-assist ventilation with load-adjustable gain factors a user-friendly mode?

OBJECTIVES: The aim of this study was to compare the number of interventions (ventilator settings and sedatives, analgesics and vasoactive medication dose manipulations) between critically ill patients on proportional-assist ventilation with load-adjustable gain factors (PAV+) and those on pressure support (PS). DESIGN: Retrospective analysis of data from a previous randomized clinical trial. METHODS: A total of 208 patients who were mechanically ventilated on controlled modes and met criteria for assisted breathing were randomized to receive either PS (n = 100) or PAV+ (n = 108). Changes in ventilator settings and in the dose of sedatives, analgesics, and vasoactive medications were identified during the period in which the patients were ventilated either with PS (30.4 +/- 17.4 h) or PAV+ (30.0 +/- 18.1 h) and classified as changes to facilitate weaning (CFW) or changes to respond to deterioration (CD). RESULTS: The mean number of changes in ventilator settings was significantly higher with PS than that with PAV+ (10.7 +/- 5.7 vs. 8.9 +/- 4.6). With PS the proportion of these changes classified as CFW was significantly lower than that with PAV+ (59.8% vs. 69.2%). Dyssynchrony as a cause of CD was more likely to occur with PS than with PAV+ (42 vs. 3%). The mean number of changes in the dose of sedatives, analgesics, and vasoactive medications was higher with PS than with PAV+, the difference being significant only for sedatives (4.06 +/- 3.8 vs. 2.82 +/- 3.4). CONCLUSIONS: Compared to PS, PAV+ is associated with fewer intervention in terms of ventilator settings and sedative dose changes.

Proportional assist ventilation with load-adjustable gain factors in critically ill patients: comparison with pressure support.

OBJECTIVES: It is not known if proportional assist ventilation with load-adjustable gain factors (PAV+) may be used as a mode of support in critically ill patients. The aim of this study was to examine the effectiveness of sustained use of PAV+ in critically ill patients and compare it with pressure support ventilation (PS). DESIGN AND SETTING: Randomized study in the intensive care unit of a university hospital. METHODS: A total of 208 critically ill patients mechanically ventilated on controlled modes for at least 36 h and meeting certain criteria were randomized to receive either PS (n = 100) or PAV+ (n = 108). Specific written algorithms were used to adjust the ventilator settings in each mode. PAV+ or PS was continued for 48 h unless the patients met pre-defined criteria either for switching to controlled modes (failure criteria) or for breathing without ventilator assistance. RESULTS: Failure rate was significantly lower in PAV+ than that in PS (11.1 vs. 22.0%, P = 0.040, OR 0.443, 95% CI 0.206-0.952). The proportion of patients exhibiting major patient-ventilator dyssynchronies at least during one occasion and after adjusting the initial ventilator settings, was significantly lower in PAV+ than in PS (5.6 vs. 29.0%, P < 0.001, OR 0.1, 95% CI 0.06-0.4). The proportion of patients meeting criteria for unassisted breathing did not differ between modes. CONCLUSIONS: PAV+ may be used as a useful mode of support in critically ill patients. Compared to PS, PAV+ increases the probability of remaining on spontaneous breathing, while it considerably reduces the incidence of patient-ventilator asynchronies.

Effects of relaxation of inspiratory muscles on ventilator pressure during pressure support.

OBJECTIVE: During pressure support ventilation (PS), an abrupt increase in ventilator pressure above the pre-set level is considered to signify expiratory muscle activity. However, relaxation of inspiratory muscles may also cause the same phenomenon, and this hypothesis has not been explored. The aim of this study is to examine the cause of this increase in ventilator pressure, during PS, in critically ill patients. DESIGN: Retrospective study. SETTING: In a university intensive care unit. METHODS: Fifteen patients instrumented with esophageal and gastric balloons, and in whom airway pressure (P (aw)) during PS exhibited an acute increase above the pre-set level towards the end of mechanical inspiration were retrospectively analyzed. For each breath, the time of the rapid increase in P (aw) was identified (t (Paw)) and, using the transdiaphragmatic (P (di)) and gastric (P (ga)) pressure waveforms, related to: (1) the end of neural inspiration (peak P (di)) and (2) the time at which P (ga) started to increase rapidly after the end of neural inspiration indicating expiratory muscle recruitment. RESULTS: The t (Paw) was observed 32+/-34ms after the end of neural inspiration, well before (323+/-182ms) expiratory muscle recruitment (identified in eight patients). There was a significant linear relationship between the rate of rise of P (aw) after t (Paw) and the rates of decline of P (di) and inspiratory flow. CONCLUSION: We conclude that, during PS ventilation, the relaxation of inspiratory muscles accounts for the acute increase in P (aw) above the pre-set level, in addition to the contribution made by the occurrence of expiratory muscle activity.

Thoracoscopic talc poudrage decreases T-lymphocytes in the peripheral blood.

BACKGROUND: Thoracoscopic talc poudrage induces peripheral blood granulocytosis and lymphopenia. The aim of this study is to investigate the type of lymphopenia in patients undergoing thoracoscopic talc poudrage. METHODS: We have measured peripheral blood lymphocyte subsets in 11 patients undergoing thoracoscopic talc poudrage, before (baseline), at 24 and 48 h after the procedure. Lymphocyte numbers were analysed by flow cytometry for the evaluation of the CD3+, CD4+, CD8+ cells (total T-lymphocytes, helper T-lymphocytes, cytotoxic T-lymphocytes, respectively), the CD19+ cells (B-lymphocytes), and the CD16+, CD56+ and CD57+ cells (NK-cells). No anti-inflammatory medication was permitted before, during or after the procedure. RESULTS: Absolute peripheral blood lymphocyte count significantly decreased following thoracoscopic talc poudrage compared to baseline values (p=0.007). Similarly, peripheral blood CD3+, CD4+ and CD8+ lymphocyte counts significantly decreased compared to baseline (p=0.005, 0.02 and 0.03, respectively) with a more prominent reduction of CD3/CD45RO memory cells. No significant difference was found in the absolute number of CD19+, CD16+, CD56+, and CD57+ cells before and after thoracoscopic talc poudrage. CONCLUSION: Patients undergoing thoracoscopic talc poudrage display peripheral blood T-lymphopenia following the procedure.

Short-term cardiorespiratory effects of proportional assist and pressure-support ventilation in patients with acute lung injury/acute respiratory distress syndrome.

BACKGROUND: Recent data indicate that assisted modes of mechanical ventilation improve pulmonary gas exchange in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Proportional assist ventilation (PAV) is a new mode of support that amplifies the ventilatory output of the patient effort and improves patient-ventilator synchrony. It is not known whether this mode may be used in patients with ALI/ARDS. The aim of this study was to compare the effects of PAV and pressure-support ventilation on breathing pattern, hemodynamics, and gas exchange in a homogenous group of patients with ALI/ARDS due to sepsis. METHODS: Twelve mechanically ventilated patients with ALI/ARDS (mean ratio of partial pressure of arterial oxygen to fractional concentration of oxygen 190 +/- 49 mmHg) were prospectively studied. Patients received pressure-support ventilation and PAV in random order for 30 min while maintaining mean airway pressure constant. With both modes, the level of applied positive end-expiratory pressure (7.1 +/- 2.1 cm H2O) was kept unchanged throughout. At the end of each study period, cardiorespiratory data were obtained, and dead space to tidal volume ratio was measured. RESULTS: With both modes, none of the patients exhibited clinical signs of distress. With PAV, breathing frequency and cardiac index were slightly but significantly higher than the corresponding values with pressure-support ventilation (24.5 +/- 6.9 vs. 21.4 +/- 6.9 breaths/min and 4.4 +/- 1.6 vs. 4.1 +/- 1.3 l . min . m, respectively). None of the other parameters differ significantly between modes. CONCLUSIONS: In patients with ALI/ARDS due to sepsis, PAV and pressure-support ventilation both have clinically comparable short-term effects on gas exchange and hemodynamics.

Respiratory load compensation during mechanical ventilation--proportional assist ventilation with load-adjustable gain factors versus pressure support.

RATIONALE: In mechanically ventilated patients respiratory system impedance may vary from time to time, resulting, with pressure modalities of ventilator support, in changes in the level of assistance. Recently, implementation of a closed-loop adjustment to continuously adapt the level of assistance to changes in respiratory mechanics has been designed to operate with proportional assist ventilation (PAV+). OBJECTIVES: The aim of this study was to assess, in critically ill patients, the short-term steady-state response of respiratory motor output to added mechanical respiratory load during PAV+ and during pressure support (PS). PATIENTS AND INTERVENTIONS: In 10 patients respiratory workload was increased and the pattern of respiratory load compensation was examined during both modes of support. MEASUREMENTS AND RESULTS: Airway and transdiaphragmatic pressures, volume and flow were measured breath by breath. Without load, both modes provided an equal support as indicated by a similar pressure-time product of the diaphragm per breath, per minute and per litre of ventilation. With load, these values were significantly lower (p<0.05) with PAV+ than those with PS (5.1+/-3.7 vs 6.1+/-3.4 cmH2O.s, 120.9+/-77.6 vs 165.6+/-77.5 cmH2O.s/min, and 18.7+/-15.1 vs 24.4+/-16.4 cmH2O.s/l, respectively). Contrary to PS, with PAV+ the ratio of tidal volume (VT) to pressure-time product of the diaphragm per breath (an index of neuroventilatory coupling) remained relatively independent of load. With PAV+ the magnitude of load-induced VT reduction and breathing frequency increase was significantly smaller than that during PS. CONCLUSION: In critically ill patients the short-term respiratory load compensation is more efficient during proportional assist ventilation with adjustable gain factors than during pressure support.

Systemic inflammatory reaction after thoracoscopic talc poudrage.

BACKGROUND: Recent studies have reported fever as a side effect of talc poudrage during thoracoscopic pleurodesis. However, thoracoscopy itself is likely to induce systemic inflammatory reaction, as it is an interventional procedure. The aim of the study was to investigate whether systemic inflammatory response is due to talc poudrage or to thoracoscopy. METHODS: We prospectively studied two groups of patients. The first group (18 patients) underwent thoracoscopic talc poudrage, and the second group (17 patients) underwent only diagnostic thoracoscopy. We measured body temperature, as well as WBC count and C-reactive protein (CRP) levels before the procedure (baseline), and at 24 and 48 h after the procedure. No antiinflammatory medication was permitted to be used before, during, or after the procedure. All patients had a 3-month follow-up. RESULTS: The baseline patient characteristics were similar in both groups. Temperature increased significantly in the thoracoscopic talc poudrage group (overall comparison, p = 0.005) especially at 9, 12, and 24 h after the procedure. Overall, the WBC count (p = 0.004), percentage of neutrophils (p = 0.03), and CRP levels (p < 0.0001) were significantly increased in the group of patients who underwent thoracoscopic talc poudrage. On the contrary, lymphocytes were significantly decreased (overall comparison, p = 0.01) in the thoracoscopic talc poudrage group during the same period. Mild side effects, such as pain during and after thoracoscopy and subcutaneous emphysema, were noted. No severe complication, such as infection or acute respiratory failure, was noted in either group during the hospitalization or during the follow-up period. CONCLUSION: According to our results, fever and systemic inflammatory reaction is due to talc poudrage and not to thoracoscopy.

Perforin expression and cytotoxic activity of sputum CD8+ lymphocytes in patients with COPD.

BACKGROUND: Previous studies have shown that the inflammatory response to cigarette smoking differs between smokers who acquire COPD and those who do not, and the CD8(+) T- lymphocytes have been identified as a key player in this response. OBJECTIVE: To investigate the cytotoxic activity and perforin expression of CD8(+) lymphocytes in the airway lumen of patients with COPD. METHODS: Thirty-six male smokers with COPD, 25 male smokers without COPD, and 10 healthy nonsmokers participated in the study. T-lymphocytes of induced sputum samples were labeled with appropriate monoclonal antibodies and measured using flow cytometry. The cytotoxic activity of CD8(+) cells was defined by incubating them with specific target cells (K562). RESULTS: The percentage and the total number of CD8(+) lymphocytes were significantly higher in COPD smokers compared to non-COPD smokers (p = 0.01 and p = 0.005, respectively) or to healthy nonsmokers (p = 0.02 and p = 0.01, respectively). Perforin expression in CD8(+) cells was significantly higher in smokers with COPD compared to the other two groups (p = 0.001). Increased cytotoxic activity of T cells was also observed in induced sputum of patients with COPD in comparison to the other two groups. CONCLUSION: CD8(+) cells are not only increased in number in sputum samples of smokers with COPD but are highly activated, expressing high levels of perforin. These findings suggest that CD8(+) T-lymphocytes play a significant role in the inflammatory process of COPD.