Safety and Tolerability of Tolvaptan in an Autosomal Dominant Polycystic Kidney Disease Spanish Cohort: A Real-World Experience.

INTRODUCTION: Autosomal dominant polycystic kidney disease (ADPKD) is the commonest inherited disorder of the kidneys. A vasopressin V2-receptor antagonist (tolvaptan) was recently approved for the treatment of ADPKD. This study aims to analyze the safety and tolerability of tolvaptan for the management of ADPKD patients in a real-world setting. METHODS: We conducted a descriptive retrospective study in ADPKD patients in an outpatient clinic setting in Spain from 2018 to 2019. Descriptive statistical analysis of demographics and clinical data, at baseline and one year after tolvaptan initiation, was assessed. Data are presented as median and interquartile range, and as frequencies for categorical variables. RESULTS: Ten patients with ADPKD were identified. At baseline median age was 49.5 (38.5-63.5) years and 60% were males. During treatment with tolvaptan, no significant aquaresis-related symptoms or hepatotoxicity were described. No serious adverse events, discontinuation, or deaths were reported during the study. CONCLUSION: Tolvaptan was well-tolerated without severe adverse events in patients with ADPKD who showed rapid disease progression criteria. Longer follow-up is required to learn about the long-term effects of this treatment.

Influence of soil texture on the distribution and availability of 238U, 230Th, and 226Ra in soils.

The influence of soil texture on the distribution and availability of (238)U, (230)Th, and (226)Ra in soils was studied in soil samples collected at a rehabilitated uranium mine located in the Extremadura region in south-west Spain. The activity concentration (Bqkg(-1)) in the soils ranged from 60 to 750 for (238)U, from 60 to 260 for (230)Th, and from 70 to 330 for (226)Ra. The radionuclide distribution was determined in three soil fractions: coarse sand (0.5-2mm), medium-fine sand (0.067-0.5mm), and silt and clay (<0.067 mm). The relative mobility of the natural radionuclides in the different fractions was studied by comparison of the activity ratios between radionuclides belonging to the same radioactive series. The lability of these radionuclides in each fraction was also studied through selective extraction from the soils using a one-step sequential extraction scheme. Significant correlations were found for (238)U, (230)Th, and (226)Ra between the activity concentration per fraction and the total activity concentration in the bulk soil. Thus, from the determination of the activity concentration in the bulk soil, one could estimate the activity concentration in each fraction. Correlations were also found for (238)U and (226)Ra between the labile activity concentration in each fraction and the total activity concentration in bulk soil. Assuming that there is some particle-size fraction that predominates in the process of soil-to-plant transfer, the parameters obtained in this study should be used as correction factors for the transfer factors determined from the bulk soil in previous studies.

[Effect of pentoxifylline on survival, cardiac function and both portal and systemic hemodynamics in advanced alcoholic cirrhosis--a randomized double-blind placebo-controlled trial]. / Effecto de la pentoxifilina en la supervivencia, la función cardiaca y en la hemodinámica portal y sistémica de la cirrosis alcohólica avanzada.

OBJECTIVE: To assess the effect of pentoxiphylline (a potent inhibitor of tumor necrosis factor alpha) on survival, on systemic and portal hemodynamics, and on cardiac function in patients with alcoholic cirrhosis. DESIGN: A randomized double-blind placebo-controlled trial. SETTING: A single center using parallel groups of patients to compare pentoxiphylline with placebo. PATIENTS: We recruited 24 patients with alcoholic cirrhosis (8 Child-Pugh B and 16 Child-Pugh C). INTERVENTIONS: Patients were randomly assigned to receive pentoxiphylline (400 mg tid; n = 12) or placebo (n = 12) over a 4-week period. OUTCOME MEASURES: The primary outcome was to extend short-term and long-term survival. Secondary outcomes included hemodynamic benefits (improvement in cardiac function and/or systemic vascular resistance index, or decrease in portal pressure). RESULTS: Portal pressure and cardiac function remained unchanged and there were no significant differences in short-term or long-term survival between treatment and placebo groups. The group on pentoxiphylline increased systemic vascular resistance and decreased cardiac indices (from 1,721 +/- 567 to 2,082 +/- 622 dyn.sec(-1) cm(-5) m(-2) and from 4.17 +/- 1.4 to 3.4 +/- 0.9 l.m(-2), p = 0.05). CONCLUSIONS: Although pentoxiphylline seems to provide some short-term hemodynamic benefits in patients with advanced alcoholic cirrhosis, this drug has no effect on survival or portal pressure in these patients.

Differential growth costs and nitrogen fixation in Cytisus multiflorus (L'Hér.) Sweet and Cytisus scoparius (L.) Link are mediated by sources of inorganic N.

Shrubby legumes in Mediterranean-type ecosystems face strong nutrient limitations that worsen in summer, when water is absent. Nitrogen-fixing legumes are likely to be able to switch between soil N and atmospheric N (N2 ) sources to adjust the C costs of N acquisition in different seasons. We investigated the utilisation of different inorganic N sources by two indigenous shrubby legumes (Cytisus multiflorus and Cytisus scoparius). Plant performance in terms of photosynthesis and biomass production was also analysed. Plants were cultivated in sterile river sand supplied with Hoagland nutrient solution, grown in N-free nutrient solution and inoculated with effective rhizobial strains from nodules of adult plants of the same species. A second treatment consisted of plants given 500 µm NH4 NO3 added into the nutrient solution. In a third treatment, plants were watered with another source of N (500 µm NH4 NO3 ) as well as being inoculated with effective rhizobial strains. The application of NH4 NO3 to the legumes resulted in a larger increase in plant dry matter. Carbon construction costs were higher in plants supplied with mineral and symbiotic N sources and always higher in the endemic C. multiflorus. Differences in photosynthesis rates were only observed between species, regardless of the N source. Non-fertilised inoculated plants had more effective root nodules and a clear dependence on N2 fixation. We propose that the ability of C. scoparius to change N source makes it a plastic species, which would account for its broader distribution in nature.

Seed germination in response to chemicals: effect of nitrogen and pH in the media.

Seed germination generally presents a peak in the next growing season after a fire. Among other factors associated with fire are the increase of soil nitrogen and changes in the pH of the soil. In this study, we addressed the question, whether or not the germination response of eight species is linked with the increase in pH and nitrogenous compounds in the germination media? We assessed the separate and combined effects of nitrogenous compounds and pH on the percentage and rate of germination of seeds of Medicago arabica (L.) Hudson, Epilobium hirsutum L., Foeniculum vulgare Miller, Daucus carota L., Thapsia villosa L., Cynosurus cristatus L., Dactylis glomerata L. and Rumex crispus L. All these species are well represented in the Mediterranean ecosystems of the central-west Spain. Water and CaCl2 were used as controls. Nitrogenous compounds increased percent germination (level) and rate in three of the species studied. High pH negatively affected the germination rate of seeds from most species, but had no effect on the per cent germination of any of the species. The higher concentration of the nutritious solutions affected negatively the germination level and rate. The different germination responses of seeds of the studied species could not be exclusively attributed to pH values in the media, whereas the amount and form of Nitrogen in the media has a greater effect on it. These differences in germination are species dependent.

Characterization and follow-up of esophagogastric junction outflow obstruction detected by high resolution manometry.

BACKGROUND: Esophagogastric junction outflow obstruction (EGJOO) is a newly described diagnostic entity growing in importance due to the use of high resolution manometry (HRM). There is little knowledge regarding its incidence, etiopathogeny, long-term evolution, and most suitable treatment. Our objective was to increase the awareness of EGJOO to optimize the management of these patients. METHODS: We conducted a historical (retrospective and prospective) study of patients diagnosed with EGJOO using HRM combined with multichannel intraluminal impedance, comparing their manometric and impedance characteristics with those of a control group. Symptoms, etiology of obstruction, acid exposure, clinical course (and its associated factors), and response to treatment were also evaluated in the EGJOO group. KEY RESULTS: Forty-four subjects were included (28 patients and 16 controls). Esophagogastric junction outflow obstruction patients presented incomplete esophageal transit more frequently than controls. Patients with structural obstruction had dysphagia more frequently than patients with functional obstruction, and different manometric, impedance, and pH-metric patterns. Over one-third of the EGJOO patients presented a spontaneous resolution of symptoms without EGJOO treatment. In the multivariate analysis, the variables associated with this spontaneous symptomatic resolution included typical symptoms of gastro-esophageal reflux disease or epigastralgia as the main symptom and resting or basal pressure of the upper esophageal sphincter <50 mmHg. CONCLUSIONS & INFERENCES: The majority of EGJOO patients presented intact peristalsis which may compensate for the lack of EGJ relaxation. In the EGJOO patients presenting favorable factors associated with a spontaneous resolution of symptoms, invasive treatments should be considered with special caution. Structural etiologies are more amenable to management, while the remainder may improve without intervention.

[Continuity and longitudinal aspects of care in general practice in four European countries]. / Continuidad y longitudinalidad en medicina general en cuatro países Europeos.

BACKGROUND: The objective of the study was to compare continuity and longitudinality of care in general practice in four European countries with a public salary model. METHODS: Descriptive and prospective study. 63 general practitioners/family physicians working in public health centers registered all encounters (direct and indirect) over a period of one week in Spain, Finland, Portugal and Sweden. RESULTS: 92% of the contacts were office encounters: 75% were direct (face to face), the average number of encounters per doctor, per week was 103. The principal problem was chronic in 42% of cases and acute in 31%. The physician has previous knowledge of the principal problem in 63% of the encounters and previous knowledge of concurrent problems in 79%. In 66% of cases the doctor has previous knowledge of the patient relatives. CONCLUSIONS: The level of continuity and longitudinality is variable; from high to low: Portugal, Spain, Sweden and Finland. In Spain the duration of the encounter is short and repeated prescription are infrequent. In Portugal there are waitings lists which implies low accessibility for acute problems. In Finland general practitioners have no patients lists and the care is des-personalized. In Sweden there are waiting lists and high use of telephone encounters.

[Healthy habits and osteoporosis prevention in perimenopausal women from rural areas]. / Hábitos saludables y prevención de la osteoporosis en mujeres perimenopáusicas de un ámbito rural.

OBJECTIVE: The probability of developing osteoporosis decreases with an adequate supply of vitamin D, a balanced diet, and increased physical activity. In this study, we evaluated whether an educational intervention improves osteoporosis-related behavior in perimenopausal women from rural areas. METHODS: A randomized experimental evaluation was performed of an educational intervention. The variables were physical activity, calcium intake and sun exposure in women from rural areas aged 45-54 years (n=216) at time 0 and 12 months after the educational intervention. In the control group (n=106), the information was sent by surface mail (month 0). In the intervention group (n=110), two interactive workshops were given (month 0). The topic of the workshops and the information sent by surface mail was healthy habits for osteoporosis prevention. RESULTS: After 12 months, the intervention group, but not the control group, had increased their physical activity (p=0.006), sun exposure (p=0.029), and calcium intake (53% to 64%). CONCLUSION: A simple educational intervention in perimenopausal women from rural areas improved healthy habits for osteoporosis prevention.

Cerebrovascular disease and gait and balance impairment in mild to moderate Alzheimer's disease.

OBJECTIVES: Gait and movement abnormalities are traditionally considered infrequent in patients with mild/moderate Alzheimer's disease (AD). However, an increased risk of falls and gait abnormalities has been detected, even in early stages of the disease. Whether these abnormalities are associated with cerebrovascular disease, which has a high prevalence in AD, remains unclear. DESIGN: Cross-sectional study. SETTING: Dementia outpatient clinics. PARTICIPANTS: 24 mild/moderate AD patients with (AD+CVD) and 20 without (AD-CVD) cerebrovascular disease without a history of stroke and antipsychotic medications. MEASUREMENTS: Physical performance, measured with the short physical performance battery [SPPB], a summary measure combining 4-meter gait speed, balance and muscle strength, and with 8-meter gait speed with a turn was compared between the two groups. RESULTS: AD+CVD patients showed a significant higher prevalence of 4-meter gait speed slower than 0.8 m/s (37.5% vs. 5%, p-value=0.01) and balance impairment (37.5% vs. 10%, p-value=0.038), as well as a slower 8-meter gait speed with a turn (mean+SD=0.6±0.2 vs. 0.8±0.2, p-value=0.024). These associations were confirmed in multivariable models. No differences were observed for muscle strength. CONCLUSION: In our sample, AD with cerebrovascular disease had worse gait and balance than AD without cerebrovascular disease. If confirmed, these results may have clinical implications, since cerebrovascular disease can be potentially prevented.

Transfer of 238U, 230Th, 226Ra, and 210Pb from soils to tree and shrub species in a Mediterranean area.

The soil-to-plant transfer factors of natural uranium isotopes ((238)U and (234)U), (230)Th, (226)Ra, and (210)Pb were studied in a disused uranium mine located in the Extremadura region in the south-west of Spain. The plant samples included trees (Quercus ilex, Quercus suber, and Eucalyptus cameldulensis) and one shrub (Cytisus multiflorus). All of them are characteristic of Mediterranean environments. The activity concentrations in leaves and fruit were determined for the tree species at different stages of growth. For the shrub, the total above-ground fraction was considered in three seasons. For old leaves and fruit, the highest activity concentrations were found in Eucalyptus cameldulensis for all the radionuclides studied, except in the case of (230)Th that presented similar activity concentrations in all of the tree species studied. In every case, the transfer to fruit was less than the transfer to leaves. In the shrub, the results depended on the season of sampling, with the highest value obtained in spring and the lowest in autumn. Important correlations were obtained for (238)U and (226)Ra between the activity ratio in soils with that in leaves or fruit.