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1.  Seizure Prognosis in Brain Tumors: New Insights and Evidence-Based Management 
The Oncologist  2014;19(7):751-759.
The choice of an antiepileptic drug (AED) for treatment of brain tumor-related epilepsy (BTE) depends on its proof of evidence in partial epilepsies in adults and individual patient features. Recent designation of a number of AEDs prompts the use of levetiracetam followed by valproic acid as the AED monotherapy of choice in BTE. In case either one is insufficiently active as a single agent or in combination, as in the case of untoward effects, alternative AEDs are lacosamide, lamotrigine, and zonisamide.
Brain tumor-related epilepsy (BTE) is common in low- and high-grade gliomas. The risk of seizures varies between 60% and 100% among low-grade gliomas and between 40% and 60% in glioblastomas. The presence of seizures in patients with brain tumors implies favorable and unfavorable factors. New-onset seizures represent an early warning sign for the presence of a brain tumor and count as a good prognostic factor for survival. Recurrence or worsening of seizures during the course of disease may signal tumor progression. Each of the modalities for tumor control (i.e., surgery, radiotherapy, chemotherapy) contributes to seizure control. Nevertheless, one third of BTE shows pharmacoresistance to antiepileptic drugs (AEDs) and may severely impair the burden of living with a brain tumor. For symptomatic therapy of BTE, seizure type and individual patient factors determine the appropriate AED. Randomized controlled trials in partial epilepsy in adults to which type BTE belongs and additional studies in gliomas indicate that levetiracetam is the agent of choice, followed by valproic acid (VPA). In the case of recurring seizures, combining these two drugs (polytherapy) seems effective and possibly synergistic. If either one is not effective or not well tolerated, lacosamide, lamotrigine, or zonisamide are additional options. A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. A practice guideline on symptomatic medical management including dose schedules of AEDs is supplied.
PMCID: PMC4077452  PMID: 24899645
Glioma; Glioblastoma; Cancer; Epilepsy; Seizures; Levetiracetam; Valproic acid; Guideline; Review
2.  Influenza Vaccine Effectiveness in Preventing Influenza A(H3N2)-Related Hospitalizations in Adults Targeted for Vaccination by Type of Vaccine: A Hospital-Based Test-Negative Study, 2011–2012 A(H3N2) Predominant Influenza Season, Valencia, Spain 
PLoS ONE  2014;9(11):e112294.
Most evidence of the effectiveness of influenza vaccines comes from studies conducted in primary care, but less is known about their effectiveness in preventing serious complications. Here, we examined the influenza vaccine effectiveness (IVE) against hospitalization with PCR-confirmed influenza in the predominant A(H3N2) 2011–2012 influenza season.
A hospital-based, test-negative study was conducted in nine hospitals in Valencia, Spain. All emergency admissions with a predefined subset of symptoms were eligible. We enrolled consenting adults age 18 and over, targeted for influenza vaccination because of comorbidity, with symptoms of influenza-like-illness within seven days of admission. We estimated IVE as (1-adjusted vaccination odds ratio)*100 after accounting for major confounders, calendar time and recruitment hospital.
The subjects included 544 positive for influenza A(H3N2) and 1,370 negative for influenza admissions. Age was an IVE modifying factor. Regardless of vaccine administration, IVE was 72% (38 to 88%) in subjects aged under 65 and 21% (−5% to 40%) in subjects aged 65 and over. By type of vaccine, the IVE of classical intramuscular split-influenza vaccine, used in subjects 18 to 64, was 68% (12% to 88%). The IVE for intradermal and virosomal influenza vaccines, used in subjects aged 65 and over, was 39% (11% to 58%) and 16% (−39% to 49%), respectively.
The split-influenza vaccine was effective in preventing influenza-associated hospitalizations in adults aged under 65. The intradermal vaccine was moderately effective in those aged 65 and over.
PMCID: PMC4230985  PMID: 25392931
3.  Tuberculosis in Patients with Haematological Malignancies 
Tuberculosis (TB) is an infectious disease that causes more than 1 million deaths worldwide every year. In addition, it is estimated that one third of the world population is infected with M. tuberculosis in a latent state, which involves an eventual risk of progressing to active TB disease. Patients with immunodeficiencies, such as those suffering from haematological malignancies, have a greater risk of progressing to TB disease once infected. It is estimated that the Relative Risk of TB disease in patients with hematologic malignancies is 2–40 times that of the general population. The diagnosis of TB in these patients is often challenging as they often present clinical characteristics that are distinct to those of patients without any other underlying disease. Mortality due to TB is higher. Therefore, it is recommended to diagnose latent TB infection and consider preventive therapy that could avoid the progression from a latent state to active TB disease. There are currently two methods for diagnosing latent TB infection: the Tuberculin Skin Test (TST) and the Interferon-Gamma Release Assays (IGRA). Due to the lack of sensitivity in patients with immunodeficient conditions, a combined TST-IGRA testing is probably the best way for latent TB diagnosis in order to gain sensitivity. Treatment of latent TB infection and TB disease should follow the general principles to that in the general population.
PMCID: PMC4010605  PMID: 24803999
4.  Atopic dermatitis and indoor use of energy sources in cooking and heating appliances 
BMC Public Health  2012;12:890.
Atopic dermatitis (AD) prevalence has considerably increased worldwide in recent years. Studying indoor environments is particularly relevant, especially in industrialised countries where many people spend 80% of their time at home, particularly children. This study is aimed to identify the potential association between AD and the energy source (biomass, gas and electricity) used for cooking and domestic heating in a Spanish schoolchildren population.
As part of the ISAAC (International Study of Asthma and Allergies in Childhood) phase III study, a cross-sectional population-based survey was conducted with 21,355 6-to-7-year-old children from 8 Spanish ISAAC centres. AD prevalence, environmental risk factors and the use of domestic heating/cooking devices were assessed using the validated ISAAC questionnaire. Crude and adjusted odds ratios (cOR, aOR) and 95% confidence intervals (CIs) were obtained. A logistic regression analysis was performed (Chi-square test, p-value < 0.05).
It was found that the use of biomass systems gave the highest cORs, but only electric cookers showed a significant cOR of 1.14 (95% CI: 1.01-1.27). When the geographical area and the mother’s educational level were included in the logistic model, the obtained aOR values differed moderately from the initial cORs. Electric heating was the only type which obtained a significant aOR (1.13; 95% CI: 1.00-1.27). Finally, the model with all selected confounding variables (sex, BMI, number of siblings, mother’s educational level, smoking habits of parents, truck traffic and geographical area), showed aOR values which were very similar to those obtained in the previous adjusted logistic analysis. None of the results was statistically significant, but the use of electric heating showed an aOR close to significance (1.14; 95% CI: 0.99-1.31).
In our study population, no statistically significant associations were found between the type of indoor energy sources used and the presence of AD.
PMCID: PMC3575224  PMID: 23088771
Atopic dermatitis; Electricity; Gas; Biomass; Indoor; Children
5.  Value of the tuberculin skin testing and of an interferon-gamma release assay in haemodialysis patients after exposure to M. tuberculosis 
BMC Infectious Diseases  2012;12:195.
Patients with end-stage renal disease (ESRD) and Mycobacterium tuberculosis infection pose a high risk of developing active TB disease. It is therefore important to detect latent TB infection (LTBI) to be able to offer treatment and prevent progression to TB disease. We assessed the value of the tuberculin skin test (TST) and of an interferon-gamma release assay (Quantiferon®-TB Gold in-Tube, QFT) for diagnosing LTBI in ESRD patients, after prolonged exposure to a highly contagious TB case in a haemodialysis unit. As a high number of patients presented erythema without induration in the TST response, this type of reaction was also analysed.
The TST and QFT were simultaneously performed twelve weeks after the last possible exposure to a bacilliferous TB patient. If the first TST (TST-1) was negative, a second TST (TST-2) was performed 15 days later to detect a booster response. A comparison was made between the TST responses (including those cases with erythema without induration) and those for the QFT. The correlation with risk of infection and the concordance between tests were both analysed.
A total of 52 patients fulfilled the inclusion criteria. Overall, 11 patients (21.2%) had a positive TST response: 3 for TST-1 and 8 for TST-2, and 18 patients (34.6%) showed a positive QFT response (p = 0.065). Erythema without induration was found in 3 patients at TST-1 and in a further 9 patients at TST-2. The three patients with erythema without induration in TST-1 had a positive TST-2 response. Concordance between TST and QFT was weak for TST-1 (κ = 0.21); it was moderate for overall TST (κ = 0.49); and it was strong if both induration and erythema (κ = 0.67) were considered.
In patients with ESRD, erythema without induration in the TST response could potentially be an indicator of M. tuberculosis infection. The QFT shows better accuracy for LTBI diagnosis than the TST.
PMCID: PMC3447656  PMID: 22905901
6.  Latent tuberculosis infection, tuberculin skin test and vitamin D status in contacts of tuberculosis patients: a cross-sectional and case-control study 
BMC Infectious Diseases  2011;11:349.
Deficient serum vitamin D levels have been associated with incidence of tuberculosis (TB), and latent tuberculosis infection (LTBI). However, to our knowledge, no studies on vitamin D status and tuberculin skin test (TST) conversion have been published to date. The aim of this study was to estimate the associations of serum 25-hydroxyvitamin D3 (25[OH]D) status with LTBI prevalence and TST conversion in contacts of active TB in Castellon (Spain).
The study was designed in two phases: cross-sectional and case-control. From November 2009 to October 2010, contacts of 42 TB patients (36 pulmonary, and 6 extra-pulmonary) were studied in order to screen for TB. LTBI and TST conversion cases were defined following TST, clinical, analytic and radiographic examinations. Serum 25(OH)D levels were measured by electrochemiluminescence immunoassay (ECLIA) on a COBAS® 410 ROCHE® analyzer. Logistic regression models were used in the statistical analysis.
The study comprised 202 people with a participation rate of 60.1%. Only 20.3% of the participants had a sufficient serum 25(OH)D (≥ 30 ng/ml) level. In the cross-sectional phase, 50 participants had LTBI and no association between LTBI status and serum 25(OH)D was found. After 2 months, 11 out of 93 negative LTBI participants, without primary prophylaxis, presented TST conversion with initial serum 25(OH)D levels: a:19.4% (7/36): < 20 ng/ml, b:12.5% (4/32):20-29 ng/ml, and c:0%(0/25) ≥ 30 ng/ml. A sufficient serum 25(OH)D level was a protector against TST conversion a: Odds Ratio (OR) = 1.00; b: OR = 0.49 (95% confidence interval (CI) 0.07-2.66); and c: OR = 0.10 (95% CI 0.00-0.76), trends p = 0.019, adjusted for high exposure and sputum acid-fast bacilli positive index cases. The mean of serum level 25(OH)D in TST conversion cases was lower than controls,17.5 ± 5.6 ng/ml versus 25.9 ± 13.7 ng/ml (p = 0.041).
The results suggest that sufficient serum 25(OH)D levels protect against TST conversion.
PMCID: PMC3292546  PMID: 22171844
Tuberculosis; Vitamin D; Latent tuberculosis infection; Tuberculin skin test conversion; Case-control study
7.  Relationship of asthma and rhinoconjunctivitis with obesity, exercise and Mediterranean diet in Spanish schoolchildren 
Thorax  2007;62(6):503-508.
Although several studies have investigated the influence of diet on asthma in schoolchildren, none of them has evaluated how obesity can modify this effect. A study was undertaken to evaluate the association of various foods and a Mediterranean diet with the prevalence of asthma and rhinoconjunctivitis, adjusting for obesity and exercise.
A cross‐sectional study was performed in 20 106 schoolchildren aged 6–7 years from eight Spanish cities. Using the ISAAC phase III questionnaire, parents reported chest and nose symptoms, food intake, weight, height and other factors, including exercise. A Mediterranean diet score was developed. A distinction was made between current occasional asthma (COA) and current severe asthma (CSA).
Independent of the amount of exercise, each Mediterranean score unit had a small but protective effect on CSA in girls (adjusted OR 0.90, 95% CI 0.82 to 0.98). Exercise was a protective factor for COA and rhinoconjunctivitis in girls and boys (the more exercise, the more protection). Obesity was a risk factor for CSA in girls (adjusted OR 2.35, 95% CI 1.51 to 3.64). Individually, a more frequent intake (1–2 times/week and ⩾3 times/week vs never/occasionally) of seafood (adjusted ORs 0.63 (95% CI 0.44 to 0.91) and 0.53 (95% CI 0.35 to 0.80)) and cereals (adjusted OR 0.56 (95% CI 0.30 to 1.02) and 0.39 (95% CI 0.23 to 0.68)) were protective factors for CSA, while fast food was a risk factor (adjusted ORs 1.64 (95% CI 1.28 to 2.10) and 2.26 (95% CI 1.09 to 4.68)). Seafood (adjusted ORs 0.74 (95% CI 0.60 to 0.92) and 0.67 (95% CI 0.53 to 0.85)) and fruit (adjusted ORs 0.76 (95% CI 0.60 to 0.97) and 0.71 (95% CI 0.57 to 0.88)) were protective factors for rhinoconjunctivitis.
A Mediterranean diet has a potentially protective effect in girls aged 6–7 years with CSA. Obesity is a risk factor for this type of asthma only in girls.
PMCID: PMC2117202  PMID: 17251311
8.  Comet Sign (and Other) in Pyemotes Dermatitis 
Emerging Infectious Diseases  2009;14(3):1759-61.
PMCID: PMC2681131  PMID: 19239781
Pyemotes; dermatitis; comet sign; epidemiology; letter
9.  Acute health effects after accidental exposure to styrene from drinking water in Spain 
We studied subjective health symptoms in a population accidentally exposed to high styrene concentrations in drinking tap water. The contamination occurred during the reparation of a water tank.
Residents of 27 apartments in two buildings using the contaminated water were contacted. A questionnaire on subjective symptoms was administered to 84 out of 93 persons living in the apartments at the time of the accident. Styrene concentration was measured in samples of water collected two days after the accident. The means of exposure associated with appearance of symptoms were examined through case-control analyses.
Styrene in water reached concentrations up to 900 μg/L. Symptoms were reported by 46 persons (attack rate 55 %). The most frequent symptoms were irritation of the throat (26%), nose (19%), eyes (18%) and the skin (14%). General gastrointestinal symptoms were observed with 11% reporting abdominal pain and 7% diarrhea. The factors most strongly associated with symptoms were drinking tap water (OR = 7.8, 95% CI 1.3–48), exposure to vapors from the basement (OR = 10.4, 2.3–47) and eating foods prepared with tap water (OR = 8.6, 1.9–40). All residents in the ground floor reported symptoms.
This accidental contamination led to very high styrene concentrations in water and was related to a high prevalence of subjective symptoms of the eyes, respiratory tract and skin. Similar exposures have been described in workers but not in subjects exposed at their residence. Various gastrointestinal symptoms were also observed in this population probably due to a local irritative effect.
PMCID: PMC156662  PMID: 12777181

Results 1-9 (9)