Plerixafor and granulocyte colony-stimulating factor for first-line steady-state autologous peripheral blood stem cell mobilization in lymphoma and multiple myeloma: results of the prospective PREDICT trial.

In Europe, the combination of plerixafor + granulocyte colony-stimulating factor is approved for the mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and myeloma whose cells mobilize poorly. The purpose of this study was to further assess the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization in European patients with lymphoma or myeloma. In this multicenter, open label, single-arm study, patients received granulocyte colony-stimulating factor (10 μg/kg/day) subcutaneously for 4 days; on the evening of day 4 they were given plerixafor (0.24 mg/kg) subcutaneously. Patients underwent apheresis on day 5 after a morning dose of granulocyte colony-stimulating factor. The primary study objective was to confirm the safety of mobilization with plerixafor. Secondary objectives included assessment of efficacy (apheresis yield, time to engraftment). The combination of plerixafor + granulocyte colony-stimulating factor was used to mobilize hematopoietic stem cells in 118 patients (90 with myeloma, 25 with non-Hodgkin's lymphoma, 3 with Hodgkin's disease). Treatment-emergent plerixafor-related adverse events were reported in 24 patients. Most adverse events occurred within 1 hour after injection, were grade 1 or 2 in severity and included gastrointestinal disorders or injection-site reactions. The minimum cell yield (≥ 2 × 10(6) CD34(+) cells/kg) was harvested in 98% of patients with myeloma and in 80% of those with non-Hodgkin's lymphoma in a median of one apheresis. The optimum cell dose (≥ 5 × 10(6) CD34(+) cells/kg for non-Hodgkin's lymphoma or ≥ 6 × 10(6) CD34(+) cells/kg for myeloma) was harvested in 89% of myeloma patients and 48% of non-Hodgkin's lymphoma patients. In this prospective, multicenter European study, mobilization with plerixafor + granulocyte colony-stimulating factor allowed the majority of patients with myeloma or non-Hodgkin's lymphoma to undergo transplantation with minimal toxicity, providing further data supporting the safety and efficacy of plerixafor + granulocyte colony-stimulating factor for front-line mobilization of hematopoietic stem cells in patients with non-Hodgkin's lymphoma or myeloma.

The predictive value of psychological assessment of candidates for gastric bypass: A medical chart review

Background and Objectives: Guidelines for bariatric surgery demand a psychological evaluation of applicants. The aim of this study was to evaluate if the presence of "psychological risk factors" predicts postoperative weight loss after gastric bypass. Methods: Medical records of obese women who underwent bariatric surgery between 2000 and 2004 were reviewed. Psychological assessment consisted of a one-hour semi-structured interview, summarized in a written report. Anthropometric assessment at baseline and 6,12,18 and 24 months after surgery included body weight, height and body mass index. Results: The mean BMI of included patients (N = 92) was 46.2 + 6,3 kg/m(2) (range 38.4-69.7). Based on the psychological assessment, 27% (N = 25) of the patients were classified as having "psychological risk factors" and 28% (N = 26) were diagnosed with a psychiatric diagnosis, most often major depression. Two years after gastric bypass, 16% of patients with "psychological risk factors" achieved an excellent result (%EWL > 75) versus 39% of those without (p < 0.05). About 1 out of 4 patients was in postoperative psychiatric treatment, but only half of them were identified as having "psychological risk factors" at baseline. Weight loss of patients initiating a psychiatric treatment only after surgery was less than of patients who continued psychiatric treatment already initiated before surgery (55.7 + 14.8 versus 66.5 + 14.2 %EWL). Conclusions: A single semi-structured psychological interview may identify patients who are at risk for diminished postoperative weight loss; however, psychological assessment did not identify those patients who were in need of a psychiatric postoperative treatment.

Motor overactivity and loss of motor circadian rhythm in fatal familial insomnia: an actigraphic study.

The 24-hour rest-activity pattern and the amount of motor activity was studied in a patient with fatal familial insomnia (FFI) by means of wrist actigraphy. During the study, the patient underwent indirect calorimetry. The 52-day recording showed severe disruption of the 24-hour rest-activity pattern with increased motor activity up to 80%. The 24-hour energy expenditure, assayed in a respiration chamber, was strikingly elevated by 60%. Chronic motor overactivity and loss of circadian rest-activity rhythm may play a role in the progressive metabolic exhaustion leading to death in FFI patients.

Estimating Gross Value Added (GVA) across multiple scales: theoretical approach and empirical validation

This paper presents an application of the Multi-Scale Integrated Analysis of Societal and Ecosystem Metabolism (MuSIASEM) approach to the estimation of quantities of Gross Value Added (GVA) referring to economic entities defined at different scales of study. The method first estimates benchmark values of the pace of GVA generation per hour of labour across economic sectors. These values are estimated as intensive variables –e.g. €/hour– by dividing the various sectorial GVA of the country (expressed in € per year) by the hours of paid work in that same sector per year. This assessment is obtained using data referring to national statistics (top down information referring to the national level). Then, the approach uses bottom-up information (the number of hours of paid work in the various economic sectors of an economic entity –e.g. a city or a province– operating within the country) to estimate the amount of GVA produced by that entity. This estimate is obtained by multiplying the number of hours of work in each sector in the economic entity by the benchmark value of GVA generation per hour of work of that particular sector (national average). This method is applied and tested on two different socio-economic systems: (i) Catalonia (considered level n) and Barcelona (considered level n-1); and (ii) the region of Lima (considered level n) and Lima Metropolitan Area (considered level n-1). In both cases, the GVA per year of the local economic entity –Barcelona and Lima Metropolitan Area – is estimated and the resulting value is compared with GVA data provided by statistical offices. The empirical analysis seems to validate the approach, even though the case of Lima Metropolitan Area indicates a need for additional care when dealing with the estimate of GVA in primary sectors (agriculture and mining).

Individual, family and environmental factors associated with pediatric excess weight in Spain: a cross-sectional study.

BACKGROUND There is a growing worldwide trend of obesity in children. Identifying the causes and modifiable factors associated with child obesity is important in order to design effective public health strategies.Our objective was to provide empirical evidence of the association that some individual and environmental factors may have with child excess weight. METHOD A cross-sectional study was performed using multi-stage probability sampling of 978 Spanish children aged between 8 and 17 years, with objectively measured height and weight, along with other individual, family and neighborhood variables. Crude and adjusted odds ratios were calculated. RESULTS In 2012, 4 in 10 children were either overweight or obese with a higher prevalence amongst males and in the 8-12 year age group. Child obesity was associated negatively with the socio-economic status of the adult responsible for the child's diet, OR 0.78 (CI95% 0.59-1.00), girls OR 0.75 (CI95% 0.57-0.99), older age of the child (0.41; CI95% 0.31-0.55), daily breakfast (OR 0.59; p = 0.028) and half an hour or more of physical activity every day. No association was found for neighborhood variables relating to perceived neighborhood quality and safety. CONCLUSION This study identifies potential modifiable factors such as physical activity, daily breakfast and caregiver education as areas for public health policies. To be successful, an intervention should take into account both individual and family factors when designing prevention strategies to combat the worldwide epidemic of child excess weight.

Association between magnesium-deficient status and anthropometric and clinical-nutritional parameters in posmenopausal women.

Background: During menopause occurs weight gain and bone loss occurs due to the hormone decline during this period and other factors such as nutrition. Magnesium deficiency suggests a risk factor for obesity and osteoporosis. OBJECTIVE: To evaluate the clinical and nutritional magnesium status in a population of postmenopausal women, assessing intake and serum levels of magnesium in the study population and correlation with anthropometric parameters such as body mass index(BMI) and body fat, and biochemical parameters associated. SUBJECTS AND METHOD: The study involved 78 healthy women aged 44-76, with postmenopausal status, from the province of Grenade, Spain. The sample was divided into two age groups: group1, aged < 58, and group 2 aged >/= 58. Anthropometric parameters were recorded and nutritional intake was assessed by 72-hour recall, getting the RDAs through Nutriber(R) program. To assess the biochemical parameters was performed a blood sample was taken. Magnesium was analyzed by flame atomic absorption spectrophotometry (FAAS) in erythrocyte and plasma wet-mineralized samples. RESULTS: Our results show that 37.85% of the total subjects have an overweight status. Magnesium intake found in our population is insufficient in 36% of women,while plasma magnesium deficiency corresponds to 23% of the population and 72% of women have deficient levels of magnesium in erythrocyte. Positive correlations were found between magnesium intake and dietary intake of calcium, of phosphorus,and with prealbumin plasma levels, as well as with a lower waist / hip ratio Magnesium levels in erythrocyte were correlated with lower triglycerides and urea values. CONCLUSION: It is important to control and monitor the nutritional status of magnesium in postmenopausal women to prevent nutritional alterations and possible clinical and chronic degenerative diseases associated with magnesium deficiency and with menopause.

Differentiation of postmitotic neuroblasts into substance P-immunoreactive sensory neurons in dissociated cultures of chick dorsal root ganglion.

Counts performed on dissociated cell cultures of E10 chick embryo dorsal root ganglia (DRG) showed after 4-6 days of culture a pronounced decline of the neuronal population in neuron-enriched cultures and a net gain in the number of ganglion cells in mixed DRG cell cultures (containing both neurons and nonneuronal cells). In the latter case, the increase in the number of neurons was found to depend on NGF and to average 119% in defined medium or 129% in horse serum-supplemented medium after 6 days of culture. The lack of [3H]thymidine incorporation into the neuronal population indicated that the newly formed ganglion cells were not generated by proliferation. On the contrary, the differentiation of postmitotic neuroblasts present in the nonneuronal cell compartment was supported by sequential microphotographs of selected fields taken every hour for 48-55 hr after 3 days of culture. Apparently nonneuronal flat dark cells exhibited morphological changes and gradually evolved into neuronal ovoid and refringent cell bodies with expanding neurites. The ultrastructural organization of these evolving cells corresponded to that of primitive or intermediate neuroblasts. The neuronal nature of these rounding up cell bodies was indeed confirmed by the progressive expression of various neuronal cell markers (150 and 200-kDa neurofilament triplets, neuron specific enolase, and D2/N-CAM). Besides a constant lack of immunoreactivity for tyrosine hydroxylase, somatostatin, parvalbumin, and calbindin-D 28K and a lack of cytoenzymatic activity for carbonic anhydrase, all the newly produced neurons expressed three main phenotypic characteristics: a small cell body, a strong immunoreactivity to MAG, and substance P. Hence, ganglion cells newly differentiated in culture would meet characteristics ascribed to small B sensory neurons and more specifically to a subpopulation of ganglion cells containing substance P-immunoreactive material.

The Effect of Valsartan versus Non-RAAS Treatment on Autoregulation of Cerebral Blood Flow.

Background: Cerebral autoregulation (CA) is a protective mechanism which maintains the steadiness of the cerebral blood flow (CBF) through a broad range of systemic blood pressure (BP). Acute hypertension has been shown to reduce the cerebrovascular adaptation to BP variations. However, it is still unknown whether CA is impaired in chronic hypertension. This study evaluated whether a strict control of BP affects the CA in patients with chronic hypertension, and compared a valsartan-based regimen to a regimen not inhibiting the renin-angiotensin-aldosterone system (non-RAAS). Methods: Eighty untreated patients with isolated systolic hypertension were randomized to valsartan 320 mg or to a non-RAAS regimen during 6 months. The medication was upgraded to obtain BP <140/90 mm Hg. Continuous recordings of arterial BP and CBF velocity (transcranial Doppler) were performed during periods of 5 minutes, at rest, and at different levels of alveolar CO(2) pressure provided by respiratory maneuvers. The dominant frequency of CBF oscillations was determined for each patient. Dynamic CA was measured as the mean phase shift between BP and CBF by cross-spectral analysis in the medium frequency and in the dominant CBF frequency. Results: Mean ambulatory 24-hour BP fell from 144/87 to 127/79 mm Hg in the valsartan group and from 144/87 to 134/81 mm Hg in the non-RAAS group (p = 0.13). Both groups had a similar reduction in the central BP and in the carotido-femoral pulse wave velocity. The average phase shift between BP fluctuations and CBF response at rest was normal at randomization (1.82 ± 0.08 s), which is considered a preserved autoregulation and increased to 1.91 ± 0.12 s at the end of study (p = 0.45). The comparison of both treatments showed no significant difference (-0.01 ± 0.17 s vs. 0.16 ± 0.16 s, p = 0.45) for valsartan versus non-RAAS groups. The plasmatic level of glycosylated hemoglobin decreased in the valsartan arm compared to the non-RAAS arm (-0.23 ± 0.06 vs. -0.08 ± 0.07%, p = 0.07). Conclusions: In elderly hypertensive men with isolated chronic systolic hypertension, CA seems efficient at baseline and is not significantly affected by 6 months of BP-lowering treatment. This suggests that the preventive effects of BP medication against stroke are not mediated through a restoration of the CA.

Reproducibility and within-day variability of body fat masurements using segmental bipolar bioelectrical impedance in women

Objective: to assess the between and within-device reproducibility, as well as within-day variability of body fat measurements. Methods: body fat percentage (%BF) was measured twice on seventeen female students aged between 18 and 20 with a body mass index of 21.9 22.6 kg/m2 (mean SD) using seven bipolar bioelectrical impedance devices (BF-306) according to the manufacturer's recommendations. Each student was also measured each hour between 7:00 and 22:00. Statistical analysis was conducted using a general linear model for repeated measurements. Results: the correlation between first and second measurements was very high (Pearson r between 0.985 and 1.000, p<0.001), as well as the correlation between devices (Pearson r between 0.986 and 0.999, all p<0.001). Repeated measurements analysis showed no differences were between devices (F test=0.83, p=0.59) or readings (first vs. second: F test=0.12, p=0.74). Conversely, significant differences were found between assessment periods throughout the day, measurements made in the morning being lower than those made in the afternoon. Assuming an overall daily average of 100 (based on all measurements), the values were 95.8 3.2 (mean SD) at 8:00 versus 101.3 3.0 at 20:00, corresponding to a mean change of 2.2 1.1 in %BF (F test for repeated values=6.58, p<0.001). Conclusions: the between and within-device reproducibility for measuring body fat is high, enabling the use of multiple devices in a single study. Conversely, small but significant changes in body fat measurements occur during the day, urging body fat measurements to be performed at fixed times.

Effect of expiratory positive airway pressure on sleep disordered breathing.

STUDY OBJECTIVES: We sought to determine the effect of expiratory positive airway pressure on end expiratory lung volume (EELV) and sleep disordered breathing in obstructive sleep apnea patients. DESIGN: Observational physiology study PARTICIPANTS: We studied 10 OSA patients during sleep wearing a facial mask. We recorded 1 hour of NREM sleep without treatment (baseline) and 1 hour with 10 cm H2O EPAP in random order, while measuring EELV and breathing pattern. RESULTS: The mean EELV change between baseline and EPAP was only 13.3 mL (range 2-25 mL). Expiratory time was significantly increased with EPAP compared to baseline 2.64 +/- 0.54 vs 2.16 +/- 0.64 sec (P = 0.002). Total respiratory time was longer with EPAP than at baseline 4.44 +/- 1.47 sec vs 3.73 +/- 0.88 sec (P = 0.3), and minute ventilation was lower with EPAP vs baseline 7.9 +/- 4.17 L/min vs 9.05 +/- 2.85 L/min (P = 0.3). For baseline (no treatment) and EPAP respectively, the mean apnea+hypopnea index (AHI) was 62.6 +/- 28.7 and 56.8 +/- 30.3 events per hour (P = 0.4). CONCLUSION: In OSA patients during sleep, the application of 10 cm H2O EPAP led to prolongation of expiratory time with only marginal increases in FRC. These findings suggest important mechanisms exist to avoid hyperinflation during sleep.

Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries.

OBJECTIVE To describe and compare the consumption of the main groups and sub-groups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis. SETTING Twenty-seven centres in 10 European countries participating in the EPIC project. SUBJECTS In total, 35 955 subjects (13 031 men and 22 924 women), aged 35-74 years, randomly selected from each EPIC cohort. RESULTS The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits. CONCLUSIONS Total vegetable and fruit intake follows a south-north gradient in both genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with V&F intake.

Trends in self-reported past alcoholic beverage consumption and ethanol intake from 1950 to 1995 observed in eight European countries participating in the European Investigation into Cancer and Nutrition (EPIC).

OBJECTIVE To describe the trends of self-reported past consumption of alcoholic beverages and ethanol intake from 1950 to 1995 within the European Prospective Investigation into Cancer and Nutrition (EPIC). DESIGN Data on consumption of beer/cider, wine and liqueur/spirits were obtained retrospectively at age 20, 30 and 40 years to calculate average consumption and ethanol intake for the time periods 1950-1975 (at age 20), 1960-1985 (at age 30) and 1970-1995 (at age 40). Regression analysis was conducted with the time period data to assess trends in past alcoholic beverage consumption and ethanol intake with time. SETTING The EPIC project. SUBJECTS In total, 392 064 EPIC participants (275 249 women and 116 815 men) from 21 study centres in eight European countries. RESULTS Generally, increases in beer/cider consumption were observed for most EPIC centres for 1950-1975, 1960-1985 and 1970-1995. Trends in wine consumption differed according to geographical location: downward trends with time were observed for men in southern European EPIC centres, upward trends for those in middle/northern European study centres. For women, similar but less pronounced trends were observed. Because wine consumption was the major contributor to ethanol intake for both men and women in most study centres, time trends for ethanol intake showed a similar geographical pattern to that of wine consumption. CONCLUSION The different trends in alcoholic beverage consumption and ethanol intake suggest that information depicting lifetime history of ethanol intake should be included in analyses of the relationship between ethanol and chronic diseases, particularly in multi-centre studies such as EPIC.

Nutrient patterns and their food sources in an International Study Setting: report from the EPIC study.

BACKGROUND Compared to food patterns, nutrient patterns have been rarely used particularly at international level. We studied, in the context of a multi-center study with heterogeneous data, the methodological challenges regarding pattern analyses. METHODOLOGY/PRINCIPAL FINDINGS We identified nutrient patterns from food frequency questionnaires (FFQ) in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study and used 24-hour dietary recall (24-HDR) data to validate and describe the nutrient patterns and their related food sources. Associations between lifestyle factors and the nutrient patterns were also examined. Principal component analysis (PCA) was applied on 23 nutrients derived from country-specific FFQ combining data from all EPIC centers (N = 477,312). Harmonized 24-HDRs available for a representative sample of the EPIC populations (N = 34,436) provided accurate mean group estimates of nutrients and foods by quintiles of pattern scores, presented graphically. An overall PCA combining all data captured a good proportion of the variance explained in each EPIC center. Four nutrient patterns were identified explaining 67% of the total variance: Principle component (PC) 1 was characterized by a high contribution of nutrients from plant food sources and a low contribution of nutrients from animal food sources; PC2 by a high contribution of micro-nutrients and proteins; PC3 was characterized by polyunsaturated fatty acids and vitamin D; PC4 was characterized by calcium, proteins, riboflavin, and phosphorus. The nutrients with high loadings on a particular pattern as derived from country-specific FFQ also showed high deviations in their mean EPIC intakes by quintiles of pattern scores when estimated from 24-HDR. Center and energy intake explained most of the variability in pattern scores. CONCLUSION/SIGNIFICANCE The use of 24-HDR enabled internal validation and facilitated the interpretation of the nutrient patterns derived from FFQs in term of food sources. These outcomes open research opportunities and perspectives of using nutrient patterns in future studies particularly at international level.

Use of Two-Part Regression Calibration Model to Correct for Measurement Error in Episodically Consumed Foods in a Single-Replicate Study Design: EPIC Case Study.

In epidemiologic studies, measurement error in dietary variables often attenuates association between dietary intake and disease occurrence. To adjust for the attenuation caused by error in dietary intake, regression calibration is commonly used. To apply regression calibration, unbiased reference measurements are required. Short-term reference measurements for foods that are not consumed daily contain excess zeroes that pose challenges in the calibration model. We adapted two-part regression calibration model, initially developed for multiple replicates of reference measurements per individual to a single-replicate setting. We showed how to handle excess zero reference measurements by two-step modeling approach, how to explore heteroscedasticity in the consumed amount with variance-mean graph, how to explore nonlinearity with the generalized additive modeling (GAM) and the empirical logit approaches, and how to select covariates in the calibration model. The performance of two-part calibration model was compared with the one-part counterpart. We used vegetable intake and mortality data from European Prospective Investigation on Cancer and Nutrition (EPIC) study. In the EPIC, reference measurements were taken with 24-hour recalls. For each of the three vegetable subgroups assessed separately, correcting for error with an appropriately specified two-part calibration model resulted in about three fold increase in the strength of association with all-cause mortality, as measured by the log hazard ratio. Further found is that the standard way of including covariates in the calibration model can lead to over fitting the two-part calibration model. Moreover, the extent of adjusting for error is influenced by the number and forms of covariates in the calibration model. For episodically consumed foods, we advise researchers to pay special attention to response distribution, nonlinearity, and covariate inclusion in specifying the calibration model.

Randomised controlled study in the primary healthcare sector to investigate the effectiveness and safety of auriculotherapy for the treatment of uncomplicated chronic rachialgia: a study protocol.

BACKGROUND Uncomplicated chronic rachialgia is a highly prevalent complaint, and one for which therapeutic results are contradictory. The aim of the present study is to evaluate the effectiveness and safety of treatment with auriculopressure, in the primary healthcare sector, carried out by trained healthcare professionals via a 30-hour course. METHODS/DESIGN The design consists of a multi-centre randomized controlled trial, with placebo, with two parallel groups, and including an economic evaluation. Patients with chronic uncomplicated rachialgia, whose GP is considering referral for auriculopressure sensory stimulation, are eligible for inclusion. Sampling will be by consecutive selection, and randomised allocation to one of the two study arms will be determined using a centralised method, following a 1:1 plan (true auriculopressure; placebo auriculopressure). The implants (true and placebo) will be replaced once weekly, and the treatment will have a duration of 8 weeks. The primary outcome measure will be the change in pain intensity, measured on a visual analogue scale (VAS) of 100 mm, at 9 weeks after beginning the treatment. A follow up study will be performed at 6 months after beginning treatment. An assessment will also be made of the changes measured in the Spanish version of the McGill Pain Questionnaire, of the changes in the Lattinen test, and of the changes in quality of life (SF-12). Also planned is an analysis of cost-effectiveness and also, if necessary, a cost-benefit analysis. DISCUSSION This study will contribute to developing evidence on the use of auriculotherapy using Semen vaccariae [wang bu liu xing] for the treatment of uncomplicated chronic rachialgia. TRIAL REGISTRATION Current Controlled Trials ISRCTN01897462.