[Temporary suspension of AstraZeneca's vaccine; a reconstruction]. / Prikpauze AstraZeneca proportioneel?

In the middle of the worldwide COVID-19 crisis, the whole of Europe was alarmed about a possible side effect of the AstraZeneca vaccine against COVID-19. Consequently, the use of this AstraZeneca vaccine was temporarily suspended in many European nations including the Netherlands. In this article, we chronologically describe the decisions that were made about the use of this vaccine in the Netherlands and we discuss the risk-benefit ratios of these actions as well as possible non-medical reasons that may explain why these actions were taken.

The Dutch Lung Cancer Audit: Nationwide quality of care evaluation of lung cancer patients.

OBJECTIVES: This study describes the initiation of the Dutch Lung Cancer Audit for Lung Oncology (DLCA-L) and reports the first results of three years of clinical auditing. METHODS: The initiation, dataset, and data quality of the DLCA-L are described. For the analyses, all patients registered from 2017 to 2019 were included. Descriptive statistics were used to assess the first outcomes of the DLCA-L, including results from quality indicators, patient- and tumor characteristics, and the real-world use of immunotherapy. RESULTS: The DLCA-L was initiated after the surgery and radiotherapy audit for lung cancer. In total, 33.788 NSCLC patients and 4.293 SCLC patients were registered in the DLCA-L from 2017 to 2019. Seventy-three (97 %) Dutch hospitals participated in the DLCA-L in 2019. The registry became nation-wide in 2020. The data quality improved over the years, with complete cases in 90 % of the NSCLC patients. In total, 15 quality indicators were established based on DLCA-L data to improve processes and clinical outcomes. An example of these quality indicators was brain imaging at diagnosis of stage III NSCLC patients, which increased from 80 % in 2017 to 90 % in 2019 and hospital variation was reduced. The DLCA-L provided data on immunotherapy use in stage IV NSCLC (n = 4.415) patients. These patients had a median age of 67 years and 11 % of the patients had an ECOG PS ≥ 2. The number of patients treated with immunotherapy in different hospitals varied between 2 patients to 163 patients per hospital. CONCLUSION: The DLCA-L has become a valuable and complete data source with national coverage in 2020. A high number of registered patients and limited missing data resulted in better insights into hospital processes and outcomes of lung cancer care. Quality indicators were, with success, used to establish improvements and minimize hospital variation. The DLCA-L also provides hospitals real-world information on the use of (systemic) therapies.

Effects of checkpoint inhibitors in advanced non-small cell lung cancer at population level from the National Immunotherapy Registry.

OBJECTIVE: Phase III studies of checkpoint inhibitors changed the therapeutic landscape for lung cancer. In 2015 the Dutch Society of Chest Physicians (NVALT) introduced a national immunotherapy registry for patients with lung cancer; quality standards for hospitals were implemented. At population level we studied clinical benefit in daily practice and in patients who are underrepresented in phase III trials. MATERIALS AND METHODS: From the initial introduction of checkpoint inhibitors in the Netherlands patients were centrally registered. Educational programs and quality control were provided under supervision of NVALT. The largest immunotherapy providing hospitals were compared to hospitals who provided less checkpoint inhibitors as marker of experience. Patients characteristics, treatment and side effects, response rate and survival were studied. RESULTS: A total of 2676 patients were registered, 2302 with follow up data were evaluated. Between October 2015 and December 2017 a gradual increase from 12 to 30 qualified hospitals showed no major toxicity differences. Toxicity led to a hospital admission rate of 9.1 with an average duration of 10.4 days. Overall tumor response was 21.8 % and median overall survival 12.6 months. Overall survival was not significantly different for patients aged ≥ 75 years, those having brain metastases or selected auto-immune diseases before start checkpoint inhibitors compared to younger patients or those without, respectively. Survival outcomes were worse in patients with PS 2+, non-smokers, and patients who received any palliative radiotherapy (HR 2.1, 95 % CI 1.7-2.7; 1.3, 95 % CI 1.0-1.6 and 1.2, 95 % CI 1.1-1.4, respectively). CONCLUSIONS: Changes in the therapeutic landscape did not lead to major differences in quality of care between hospitals. Elderly patients, those with brain metastases or selected auto-immune disease underrepresented in clinical trials did not do worse on checkpoint inhibitors, except for those with PS 2 + .

DNA hypermethylation analysis in sputum for the diagnosis of lung cancer: training validation set approach.

BACKGROUND: Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer. METHODS: DNA hypermethylation of RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities. RESULTS: In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set. CONCLUSIONS: Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks.

BACKGROUND/OBJECTIVES: Fabuless (Olibra) is a commercially structured lipid emulsion, claimed to be a food ingredient that is effective for food intake and appetite reduction. The present study assessed its efficacy in a yoghurt-based mini-drink undergoing low or minimal food manufacturing (thermal and shear) processes. SUBJECTS/METHODS: Study 1: Twenty-four healthy volunteers (16 female, 8 male; age: 18-47 years; body mass index (BMI): 17-28 kg m(-2)) took part in a randomised, placebo-controlled, double-blind parallel crossover trial. Consumption of a minimally processed 'preload' mini-drink (containing two different doses of Fabuless or a control fat) at 2 h after breakfast was followed by appetite and mood ratings, and food intake measured in ad libitum meals at 3 and 7 h post consumption of the preload. Study 2: As Study 1 (16 female, 8 male; age: 20-54 years; BMI: 21-30 kg m(-2)). A chilled, virtually unprocessed, preload breakfast mini-drink (containing minimally processed Fabuless or a control fat) was provided 5 min after a standardised breakfast, followed by appetite and mood ratings, and food intake measured in ad libitum meals at 4 and 8 h post consumption of the preload. RESULTS: The structured lipid emulsion tested had no significant effect on the primary measures of food intake or appetite. CONCLUSIONS: Even when exposed to minimal food-manufacturing conditions, Fabuless showed no efficacy on measures of appetite and food intake.

Review and meta-analysis of the short-term effects of a vegetable oil emulsion on food intake.

Several short-term studies have investigated the effects of a vegetable oil emulsion on subsequent food intake, although findings have been inconsistent. This work aimed to review all studies, and investigate differences in study outcomes based on methodology. All known studies were identified. Data were abstracted from published studies (n = 7). Details of unpublished studies were gained from investigators/sponsors (n = 5), or were unavailable for reasons of confidentiality (n = 4). Available data were combined using meta-analyses. A combined appetite suppressant effect of the emulsion compared with control was found for test meal intake at approximately 4, 12 and 36 h post-treatment: smallest combined mean difference (random effects model) = 0.53 MJ (95% confidence interval 0.20, 0.86), P < 0.01. However, considerable heterogeneity (variability) between study results was also found (smallest I(2) = 94%, P < 0.01), questioning the predictive validity of the above findings. Meta-regression suggested this heterogeneity to be related to differences in the processed nature of the product, treatment dose and in particular year of study (smallest B = 0.54, 95% confidence interval 0.06, 1.03, P = 0.04), although again heterogeneity was found. The only consistent finding was a lack of effect on food intake 4 h post-preload in studies conducted after 2003. These results suggest a small but inconsistent appetite suppressant effect of the vegetable oil emulsion. However, due to the large heterogeneity, no definitive conclusions can be drawn.

Quality of life, geriatric assessment and survival in elderly patients with non-small-cell lung cancer treated with carboplatin-gemcitabine or carboplatin-paclitaxel: NVALT-3 a phase III study.

BACKGROUND: Elderly patients with advanced non-small-cell lung cancer (NSCLC) may derive similar benefit from platinum-based chemotherapy as younger patients. Quality of life (QoL) and comprehensive geriatric assessment (CGA) is often advocated to assess benefits and risks. PATIENTS AND METHODS: A total of 181 chemotherapy-naive patients [≥70 years, performance score (PS) of 0-2] with stage III-IV NSCLC received carboplatin and gemcitabine (CG) (n = 90) or carboplatin and paclitaxel (CP) (n = 91) every 3 weeks for up to four cycles. Primary end point was change in global QoL from baseline compared with week 18. Pretreatment CGA and mini geriatric assessment during and after treatment were undertaken. A principal component (PC) analysis was carried out to determine the underlying dimensions of CGA and QoL and subsequently related to survival. RESULTS: There were no changes in QoL after treatment. The number of QoL responders (CG arm, 12%; CP arm, 5%) was not significantly different. CGA items were only associated with neuropsychiatric toxicity. Quality-adjusted survival was not different between treatment arms. The PC analysis derived from nine CGA, six QoL and one PS score indicated only one dominant dimension. This dimension was strongly prognostic, and physical and role functioning, Groningen Frailty Indicator and Geriatric Depression Scale were its largest contributors. CONCLUSIONS: Paclitaxel or gemcitabine added to carboplatin did not have a differential effect on global QoL. CGA was associated with toxic effects in a very limited manner. CGA and QoL items measure one underlying dimension, which is highly prognostic.

No efficacy of processed Fabuless (Olibra) in suppressing appetite or food intake.

BACKGROUND/OBJECTIVES: To investigate the feasibility of Fabuless (previously called Olibra and Reducal) as a food ingredient for food intake and appetite reduction, by assessing the effects of food processing on efficacy. SUBJECTS/METHODS: In total, 24 healthy volunteers (16 female, 8 male; age: 18-43 years; body mass index: 18-37 kg/m(2)) took part in a randomized, placebo-controlled, double-blinded, cross-over trial. Yoghurt-based meal replacement drinks (containing processed or unprocessed Fabuless, or a control fat) were followed by an ad libitum lunch and evening meal (dinner). Key outcome measures were energy intake and self-reported appetite ratings. RESULTS: Compared with control, only unprocessed Fabuless reduced subsequent energy intake, although only during dinner (P < 0.01; control, processed and unprocessed: 4.3, 3.9 and 4.2 MJ, respectively) and not during lunch (3.6, 3.7 and 3.6 MJ). Self-reported appetite scores did not differ between treatments. CONCLUSIONS: Although modest effects of unprocessed Fabuless were seen on food intake, but not on appetite, the ingredient was not robust to common food-manufacturing processes (thermal and shear processing). Claims on reduced food intake and appetite relating to this ingredient in food products are, therefore, only valid if functionality has been demonstrated after all relevant processing and storage steps.

Sildenafil treatment in COPD does not affect stroke volume or exercise capacity.

In chronic obstructive pulmonary disease (COPD) patients, stroke volume response to exercise is impaired. The aim of the present study was to investigate whether 3 months of sildenafil treatment improves stroke volume and, if so, whether this improvement is related to the pulmonary artery pressure and translated into an improved exercise capacity. A total of 15 stable COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) underwent right heart catheterisation at rest and during exercise. Stroke volume was assessed by magnetic resonance imaging (MRI) at rest and during submaximal exercise in the supine position and compared with eight age-matched controls. Additionally, a cardiopulmonary exercise test and a 6-min walking distance test were performed. Exercise tests and MRI were repeated after 12 weeks of oral therapy with 50 mg sildenafil three times daily. Stroke volume in COPD patients was significantly lower than in healthy controls (62+/-12 versus 81+/-22 mL at rest and 70+/-15 versus 101+/-28 mL during exercise). Pulmonary hypertension (PH) was diagnosed in nine patients and was absent in six. Treatment with sildenafil had no effect on stroke volume or exercise capacity. Although the stroke volume was lower in COPD patients with associated PH in comparison with non-PH patients, there was no difference in treatment response between both groups. In the present group of 15 chronic obstructive pulmonary disease patients, a reduced stroke volume was found at rest and during exercise. Neither stroke volume nor exercise capacity were improved by 3 months of sildenafil therapy.

Influence of a TiCl4 post-treatment on nanocrystalline TiO2 films in dye-sensitized solar cells.

In this study, the influence of the TiCl(4) post-treatment on nanocrystalline TiO(2) films as electrodes in dye-sensitized solar cells is investigated and compared to nontreated films. As a result of this post-treatment cell efficiencies are improved, due to higher photocurrents. On a microscopic scale TiO(2) particle growth on the order of 1 nm is observed. Despite a corresponding decrease of BET surface area, more dye is adsorbed onto the oxide surface. Although it seems trivial to match this finding with the improved photocurrent, this performance improvement cannot be attributed to higher dye adsorption only. This follows from comparison between incident photon to current conversion efficiency (IPCE) and light absorption characteristics. Since the charge transport properties of the TiO(2) films are already more than sufficient without treatment, the increase in short circuit current density J(SC) cannot be related to improvements in charge transport either. Transient photocurrent measurements indicate a shift in the conduction band edge of the TiO(2) upon TiCl(4) treatment. It is concluded that the main contribution to enhanced current originates from this shift in conduction band edge, resulting in improved charge injection into the TiO(2).

Is a patient's self-reported health-related quality of life a prognostic factor for survival in non-small-cell lung cancer patients? A multivariate analysis of prognostic factors of EORTC study 08975.

BACKGROUND: The aim of this prognostic factor analysis was to investigate if a patient's self-reported health-related quality of life (HRQOL) provided independent prognostic information for survival in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Pretreatment HRQOL was measured in 391 advanced NSCLC patients using the EORTC QLQ-C30 and the EORTC Lung Cancer module (QLQ-LC13). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap validation technique was used to assess the stability of the outcomes. RESULTS: The final multivariate Cox regression model retained four parameters as independent prognostic factors for survival: male gender with a hazard ratio (HR) = 1.32 (95% CI 1.03-1.69; P = 0.03); performance status (0 to 1 versus 2) with HR = 1.63 (95% CI 1.04-2.54; P = 0.032); patient's self-reported score of pain with HR= 1.11 (95% CI 1.07-1.16; P < 0.001) and dysphagia with HR = 1.12 (95% CI 1.04-1.21; P = 0.003). A 10-point shift worse in the scale measuring pain and dysphagia translated into an 11% and 12% increased in the likelihood of death respectively. A risk group categorization was also developed. CONCLUSION: The results suggest that patients' self-reported HRQOL provide independent prognostic information for survival. This finding supports the collection of such data in routine clinical practice.

Effects of perennial ryegrass cultivars on milk yield and nitrogen utilization in grazing dairy cows.

The effects of 4 diploid perennial ryegrass cultivars that differed in water-soluble carbohydrate (WSC) concentrations on milk yield and nitrogen (N) utilization in dairy cows were evaluated in a 2-yr grazing experiment. Twelve lactating dairy cows were assigned to 1 cultivar for a 2-wk period in a 4 x 4 Latin square design with 3 replicates. Each year, the experiment lasted 8 wk. Swards were in a vegetative stage throughout the experiment. Herbage constituents were determined, and DM intake was estimated with the n-alkane technique. Nitrogen utilization was calculated as N excreted in milk divided by N intake, assuming a zero N retention. Two cultivars had consistently higher WSC concentrations and slightly lower neutral detergent fiber concentrations than the other 2 cultivars. The ranking of the cultivars in chemical composition traits in both years was rather consistent. Cows grazing the cultivar with the lowest concentration of WSC had the lowest herbage DM intake, N intake, milk yield, and milk N yield in 2002, but with a similar difference in WSC concentration, no differences among cultivars were found in 2003. In both years, milk urea N concentration was slightly higher for cows grazing the cultivar with the lowest WSC concentration, although it was significant only in 2003. Nitrogen utilization (N milk:N intake, g/g) varied between 0.241 and 0.246 in 2002 and between 0.190 and 0.209 in 2003, and in both years there was no effect of cultivar. At relatively high N concentrations in grass and only small differences among cultivars in neutral detergent fiber concentrations, cultivars with an elevated WSC concentration did not increase N utilization in grazing dairy cows.

Docetaxel and cisplatin as induction chemotherapy in patients with pathologically-proven stage IIIA N2 non-small cell lung cancer: a phase II study of the European organization for research and treatment of cancer (EORTC 08984).

The objective of this phase II study was to document activity and toxicity of docetaxel and cisplatin as induction chemotherapy in patients with stage IIIA N2 non-small cell lung cancer (NSCLC) before definitive local treatment. Forty-six chemotherapy-nai ve patients (median age 60 years) were included. Treatment consisted of 3 cycles of docetaxel (85 mg/m2 on day 1), followed by cisplatin (40 mg/m2/day on days 1 and 2) every 21 days. Grade 3-4 leukopenia and neutropenia occurred in 45.7% and 65.2% of the patients, respectively. Among 8 cases of febrile neutropenia (17.4%), one (2.2%) resulted in early death. Common grade 3-4 non-haematological toxicities were nausea (17.4%) and vomiting (13%). Eighty-five percent of the patients received three courses; six stopped prematurely due to toxicity, one due to protocol violation. Response rate was the primary endpoint of this study. Considering eligible patients (n=40), 18 responses (1 complete and 17 partial responses) were observed (response rate 45%; 95% Confidence interval (CI): 29.3%-61.5%). In stage IIIA-N2 NSCLC patients, docetaxel-cisplatin could be administered and demonstrated manageable toxicity with modest efficacy.

Effects of perennial ryegrass cultivars on intake, digestibility, and milk yield in dairy cows.

The effects of 8 diploid perennial ryegrass (Lolium perenne L.) cultivars on dry matter (DM) intake, DM digestibility, and milk yield (MY) of dairy cows were evaluated in the summer of 2000 and 2001. Each summer, herbage was harvested daily and stall-fed to 12 dairy cows during six 2-wk periods. Six cultivars were fed in 3 periods (1, 3, and 5) according to a double 3 x 3 Latin square design. In the other periods (2, 4, and 6), 2 cultivars were fed in a repeated measurement design. Herbage mass and leaf blades in the sward canopy varied among cultivars, but differences were not consistent between years. The largest differences in herbage composition were found in water-soluble carbohydrate content, followed by crude protein content. only small differences were found in the neutral detergent fiber (NDF) content. A higher water-soluble carbohydrate content was found in 2 cultivars in both years, whereas ranking of cultivars in crude protein and NDF content was not consistent with years. Dry matter intake and MY were not affected by cultivar. In both years, DM digestiblity was high (>77%), with very small differences among cultivars in 2000 (<0.5%) and larger differences in 2001 (up to 4%). This was associated with a delayed heading date in 2001, resulting in larger differences in leaf blades and NDF content among cultivars. It may be concluded that the 8 cultivars used in our experiments do not provide grass breeders with encouraging evidence to include selection criteria for an increased DM intake, DM digestibility, and MY in their grass breeding schemes.

Comparison of techniques for estimating herbage intake of grazing dairy cows.

For estimating herbage intake during grazing, the traditional sward cutting technique was compared in grazing experiments in 2002 and 2003 with the recently developed n-alkanes technique and with the net energy method. The first method estimates herbage intake by the difference between the herbage mass before and after grazing and the regrowth between the 2 points in time. The second technique estimates herbage intake by the ratio of a dosed even-chain synthetic n-alkane (C32) and a naturally occurring odd-chain n-alkane (C31 or C33) in the herbage and feces. The third technique calculated the intake from the animal's energy requirements for milk production and maintenance. The sward cutting technique estimated herbage intake with the highest coefficient of variation and had different results in the 2 experimental years. The n-alkanes method yielded less variable results, whereas the net energy method gave the least variable results. In 2002, the estimates of the alkane ratio C32:C33 were best related with estimations of the net energy method. In 2003, the estimates of the alkane ratio C32:C31 were best related. The estimate based on the alkane ratio C32:C33 had a lower coefficient of variation than the one based on the alkane ratio C32:C31. Therefore, the C32:C33 alkane method was considered to be a better direct estimator for herbage intake by grazing lactating dairy cows.

Mood and cognitive performance effects of "energy" drink constituents: caffeine, glucose and carbonation.

Three studies using healthy volunteers (n = 271) investigated the effects of caffeine, carbohydrates and carbonation in functional "energy" drinks (EDs) with the aim of determining their benefit in every-day life. The results showed caffeine to be the main ED constituent responsible for the effects found, with possible minor, relatively weak effects of carbohydrates. EDs were found to improve and/or maintain mood and performance during fatiguing and cognitively demanding tasks relative to placebo. In terms of absolute values, EDs maintained levels of arousal compared to a deterioration in arousal where placebo was consumed. These effects were found in caffeine-deprived participants, and so may be largely due to "withdrawal reversal". There were only minor differences in the effects of water vs. "sensory-matched" placebo, supporting previous findings indicating that the type of placebo does not alter the conclusions drawn about the effects of the full ED. Finally, carbonation had various effects on mood, some of which were present immediately following consumption, others were consistent with slower absorption of caffeine (and possibly carbohydrates) from carbonated drinks.

Electrical impedance tomography to measure pulmonary perfusion: is the reproducibility high enough for clinical practice?

A possible clinical application of electrical impedance tomography (EIT) might be to monitor changes in the pulmonary circulation, provided the reproducibility of the EIT measurement is adequate. The purpose of this study was threefold: the intra- and inter-investigator variability of repeated measurements was investigated. Three different regions of interest (ROI) were analysed to assess the optimal ROI. Twenty-four healthy subjects and six patients were included. The Sheffield applied potential tomograph (DAS-01P, IBEES, Sheffield, UK) was used. Electrodes were attached by investigator A, and duplicate EIT measurements were performed. After detachment and 45 min of rest, the protocol was repeated by another investigator B, and afterwards by the initial investigator A. Three ROIs were analysed: whole circle, 'inner half circle' and contour. The mean difference in impedance changes between observers is presented in arbitrary units (AU) +/- SD. Finally, the influence of age, body composition and sex on the EIT result was examined. For the contour ROI, the mean difference for the intra-investigator situation was -1.44 x 10(-2) +/- 18.45 x 10(-2) AU (-0.7 +/- 9.0%), and was 5.46 x 10(-2) +/- 21.66 x 10(-2) AU (2.7 +/- 10.8%) for the inter-investigator situation. The coefficient of reproducibility of the intra- and inter-investigator reproducibility varied between 0.89 and 0.97 for all ROIs (P < 0.0001). There is a relation between impedance change and age (correlation coefficient r = -0.63, P < 0.01 for contour ROI), and between impedance change and body mass index (BMI) (r = -0.53, P < 0.05). We found a significant difference in mean impedance change between groups of males and females. In conclusion, EIT results are highly reproducible when performed by the same investigator as well as by two different investigators.

Epoprostenol-induced pulmonary vasodilatation in patients with pulmonary hypertension measured by electrical impedance tomography.

Electrical impedance tomography (EIT) has been proposed as a method to monitor dynamic changes in the pulmonary vascular bed. In this study we examined the validity of EIT in the measurement of pulmonary vasodilatation in eight patients with primary and secondary pulmonary hypertension when given the vasodilating agent epoprostenol (Flolan). Therefore, catheterization of the pulmonary artery was performed in the ICU and the cardiac output was measured by means of the Fick method. The pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) were determined. Epoprostenol was given in increasing doses to test reversibility of pulmonary hypertension. The maximum test dose was 12 ng kg(-1) min(-1). During each step simultaneous EIT (DAS-01 P Portable Data Acquisition System, Sheffield, England) measurements were performed with the 16 electrodes equidistantly positioned in the third intercostal space. The maximal systolic impedance change, relative to end-diastole, deltaZperf, was chosen as a measure of pulmonary perfusion. The impedance change between baseline and highest tolerable epoprostenol concentration was compared with the change in PVR. The mean PVR (dyn s/cm5) decreased from 636 (+/-399) to 366 (+/-242); p < 0.01. DeltaZperf (in arbitrary units) for the whole patient group increased from 901 (+/-295) x 10(-3) to 1082 (+/-472) x 10(-3) (p<0.05). Only one patient showed a reduction in pulmonary artery pressure >20%, which is defined as significant vasodilatation. A strong relationship was found between the impedance changes and the change in PVR and mPAP in the patient with a significant vasodilatation on epoprostenol. From these results we conclude that EIT is a reliable method to measure blood volume changes due to pharmacologically induced vasodilatation in the pulmonary bed.

Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.

RATIONALE: Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). OBJECTIVE: This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. METHODS: This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). RESULTS: Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. CONCLUSIONS: After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.