OBJECTIVE:To assess lipoatrophy, other toxicities, and efficacy associated with abacavir as compared with stavudine in HIV-infected antiretroviral-naive patients.
METHODS:This was a prospective, ...randomized, open trial, stratified by viral load and CD4 cell count, conducted January 2001 to July 2004. Two hundred thirty-seven adult patients with HIV infection initiating antiretroviral therapy were assigned to receive abacavir (n = 115) or stavudine (n = 122), both combined with lamivudine and efavirenz. The primary endpoint was the proportion of patients with lipoatrophy as assessed by physician and patient observation at 96 weeks.
RESULTS:A lower proportion of patients assigned to abacavir developed clinical signs of lipoatrophy (4.8% vs. 38.3%; P < 0.001). These observations were confirmed by anthropometric data. Dual energy x-ray absorptiometry (DEXA) scans performed in 57 patients showed significantly greater total limb fat loss in the stavudine arm (−1579 vs. 913 g; P < 0.001). The lipid profile in abacavir patients presented more favorable changes in the levels of triglycerides (P = 0.03), high-density lipoprotein cholesterol (HDLc; P < 0.001), and apolipoprotein A1 (P < 0.001) as well as in the ratio between total cholesterol and HDLc (P = 0.005). Throughout the study, a higher proportion of patients in the stavudine group received lipid-lowering agents as compared to the abacavir group (17% vs. 4%; P = 0.002). Similar virologic and immunologic responses were observed.
CONCLUSIONS:Assuming the limitations inherent to clinical assessment, this study shows a notably weaker association of abacavir with lipoatrophy than stavudine. DEXA scans and anthropometric measurements supported the clinical findings. In addition, the lipid changes that occurred were more favorable in patients receiving abacavir.
BACKGROUND: Evidence suggests that general practitioners (GPs) fail to diagnose up to half of common mental disorder cases. Yet no previous research has systematically summarized the evidence in the ...case of anxiety disorders. The aim of this review was to systematically assess and meta-analyze the diagnostic accuracy of GPs' assisted (i.e., using severity scales/diagnostic instruments) and unassisted (without such tools) diagnoses of anxiety disorders. METHODS: Systematic review (PROSPERO registry CRD42013006736) was conducted. Embase, Ovid Journals - Ovid SP Medline, Pubmed, PsycINFO, Scopus, Web of Science, and Science Direct were searched from January 1980 through June 2014. Seven investigators, working in pairs, evaluated studies for eligibility. The quality of included studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool version 2 (QUADAS-2). The main outcome measures were sensitivity and specificity of clinical diagnoses of any anxiety disorder. We pooled sensitivity and specificity levels from included studies using bivariate meta-analyses. RESULTS: Twenty-four studies were included in the meta-analysis with a total sample of 34,902 patients. Pooled sensitivity and specificity were estimated at 44.5% (95% CI 33.7-55.9%) and 90.8% (95% CI 87-93.5%). GPs' sensitivity was higher when diagnoses were assisted (63.6%, 95% CI 50.3-75.1%) than when unassisted (30.5%, 95% CI 20.7-42.5%) to the expense of some specificity loss (87.9%, 95% CI 81.3-92.4% vs. 91.4%, 95% CI 86.6-94.6%, respectively). Identification rates remained constant over time (P-value = .998). CONCLUSIONS: The use of diagnostic tools might improve detection of anxiety disorders in "primary care."
This study was funded by a grant from the Spanish Ministry of Health, Instituto de Salud Carlos III, FEDER PI10/00530, Fondo de Investigación Sanitaria ISCIII (FI11/00154), and by DIUE Generalitat de Catalunya (2014 SGR 748)
BACKGROUND: Reproductive factors are well known risk factors for breast cancer; however, little is known about how genetic variants in hormonal pathways interact with that relationship. METHODS: One ...thousand one hundred thirty nine cases of breast cancer in women and 1322 frequency-matched controls were compared. Genetic variants in hormonal pathways (identified in the Kyoto Encyclopedia of Genes and Genomes) were screened according to their relationship with breast cancer using the Cochran-Armitage statistic. Information on reproductive factors was obtained using a face-to-face questionnaire. The interaction among the selected genetic variants and reproductive factors was tested with logistic regression. RESULTS: Concerning C allele in rs2229712, compared to nulliparity in non-carriers the ORs for 1-2 and > 2 deliveries were 0.48 (0.28-0.81) and 0.34 (0.19-0.59), and in C carriers they were 0.92 (0.42-1.98) and 0.71 (0.31-1.61). Similar results were found in women carrying the C allele in rs1269851. Carriers of Allele T in rs35652107 and allele C in rs6018027 had the delivery number effect more pronounced. CONCLUSIONS: The number of deliveries had a dose-response protective effect on breast cancer; women carrying C allele in rs2229712 did not benefit from this protective effect.
Background: While a low CD4/CD8 ratio during HIV treatment correlates with immunosenescence, its value in identifying patients at an increased risk for clinical events remains unclear. Methods: We ...analyzed data from the CoRIS cohort to determine whether CD4 count, CD8 count, and CD4/CD8 ratio at year two of antiretroviral therapy (ART) could predict the risk of serious non-AIDS events (SNAEs) during the next five years. These included major adverse cardiovascular events, non-AIDS-defining malignancies, and non-accidental deaths. We used pooled logistic regression with inverse probability weighting to estimate the survival curves and cumulative risk of clinical events. Findings: The study included 4625 participants, 83% male, of whom 200 (4.3%) experienced an SNAE during the follow-up period. A CD4/CD8 ratio <0.3 predicted an increased risk of SNAEs during the next five years (OR 1.63, 95% CI 1.03–2.58). The effect was stronger at a CD4/CD8 ratio cut-off of <0.2 (OR 3.09, 95% CI 1.57–6.07). Additionally, low CD4 count at cut-offs of <500 cells/μL predicted an increased risk of clinical events. Among participants with a CD4 count ≥500 cells/μL, a CD8 count ≥1500 cells/μL or a CD4/CD8 ratio <0.4 predicted increased SNAE risk. Interpretation: Our results support the use of the CD4/CD8 ratio and CD8 count as predictors of clinical progression. Patients with CD4/CD8 ratio <0.3 or CD8 count ≥1500/μL, regardless of their CD4 count, may benefit from closer monitoring and targeted preventive interventions. Funding: This work was supported by CIBER (CB 2021), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea—NextGenerationEU; by the Spanish AIDS Research Network (RIS) RD16/0025/0001 project as part of the Plan Nacional R + D + I, and cofinanced by Instituto de Salud Carlos III (ISCIII)- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER), ISCIII projects PI18/00154, PI21/00141, and ERDF, “A way to make Europe”, ICI20/00058.
A 50-year-old patient, a smoker, was admitted to the hospital, with a solitary scalp lump. Subcutaneous lumps of the scalp are common but usually benign; however, the painless lump in our patient ...turned out to be a malignant osteolytic lesion of the skull. Frontal bone was involved, and the disease had spread to the dura. Neuroimaging showed osteolytic lesions involving the axial skeleton, skull and several vertebrae. MRI showed the involvement of the second cervical vertebra, which prompted us to start treatment with dexamethasone. Since the spinal cord was not involved, Oncologists decided not to start radiotherapy treatment until we had reached the final diagnosis. A frontal bone biopsy confirmed the diagnosis of lung carcinoma. Chest X-ray did not identify the pulmonary nodule, but CT scan revealed a 1 cm peripheral, spiculated, pulmonary nodule within a pathological parenchyma (severe diffuse pulmonary emphysema).
Cyclosporin A (CyA) loaded poly(lactic acid)–poly(ethylene glycol) (PLA–PEG) micro- and nanoparticles have been developed using an emulsion-solvent evaporation method. Physico-chemical properties, ...peptide loading content and in vitro release profiles of these novel CyA carriers were compared with those corresponding to conventional PLA micro- and nanoparticles. Results obtained confirm the previously described disposition of PEG chains on the surface of the PLA–PEG formulations. In addition, they revealed the presence of CyA molecules on the surface of both PLA and PLA–PEG systems. Further determination of the surface chemical composition by electron spectroscopy for chemical analysis (ESCA) allowed us to quantify the amount of CyA in the nanospheres’ top layers, this amount being higher for nanoparticles than for microparticles, and higher for the PLA systems than for those based on PLA–PEG. In vitro release experiments revealed that PLA–PEG particles provided a more adequate control of CyA release than conventional PLA micro- and nanoparticles. Physico-chemical characterization of the systems during the release studies showed that the developed PLA and PLA–PEG micro- and nanoparticles were not degraded, which suggest a diffusion-mediated release mechanism. Furthermore, we have hypothesized that the hydrophilic outer shell of PEG provides a stationary layer for the diffusion of CyA.
Abstract 3827
Myelodysplastic syndromes (MDS) are a heterogeneous group of hematological disorders in which diagnosis, risk stratification, and treatment selection are based on morphological and ...cytogenetic studies in bone marrow (BM) samples. MDS are characterized by several recurrent chromosomal abnormalities, most of them unbalanced, with a widely variable prognosis. The assessment of these genomic defects is essential for a correct risk stratification of these patients. However, conventional cytogenetic (CC) techniques are not sufficient for the study of all MDS patients, because of the high proportion of normal karyotypes (40–50%) and unsuccessful cytogenetics (10%) (defined as the absence of mitosis). Array-based comparative genomic hybridization (aCGH) technology allows the screening of copy number changes among the whole genome in one single experiment and offers a higher resolution than conventional cytogenetics.
To assess the potential application of aCGH in the clinical diagnosis of MDS as complementary tool to conventional cytogenetics.
The study cohort comprises a total of 263 patients: MDS (203) and MDS/MPN (60) patients that have been previously studied by CC and FISH. Among the whole series, 33 (12.5%) patients had no successful cytogenetic results due to the absence of mitosis. In the remaining 230 patients with evaluable metaphases, 42 (16%) had an aberrant, while 188 (71.5%) presented a normal karyotype. Within this last group, 141 had ≥20 good-quality metaphases evaluated, 37 had 10–20 metaphases studied, and 10 patients had ≤10 successful metaphases.
Copy number changes were analysed in all patients included in the study using NimbleGen Human CGH 12×135K Whole-Genome Tiling Array (Roche NimbleGen). Sex-matched human commercial DNA samples were used as reference. Data were analysed using the segMNT algorithm in NimbleScanv2.6 Software. Subsequently all genomic abnormalities found by aCGH analysis were confirmed by FISH.
Using aCGH methodology, copy number changes (greater than 600 bp) were detected in 54 patients of the global series: 4.3% of the normal karyotype patients, 88.1% of cases with abnormal cytogenetics, and 27.3% of patients with unsuccessful cytogenetics. Overall a high correlation (94.3%) between the cytogenetic changes observed by CC and CGH arrays was observed. Thus aCGH analysis revealed the same genomic abnormalities showed by CC in 88.1% of patients. In the remaining 11.9% genomic results were discordant between aCGH and CC, because of the presence of balanced translocations, not assessable by aCGH, and clonal cell populations below 30%. Furthermore, additional genomic abnormalities (n=36) not detected by CC were found by aCGH. The most frequent aberrations were losses affecting chromosomes 5 (33%), 7/7q (17%), 20q (14%), and Y (14%), as well as gains involving chromosome 8 (14%). Interestingly, other abnormalities, mainly losses, were found in chromosomes 4, 12, and 17.
Focusing on the 188 patients with normal karyotype by CC, the aCGH profiling results were concordant with cytogenetics in 98% of those patients with ≥20 metaphases studied and in 92% of those with 10–20 metaphases. However, only 80% of those patients with ≤10 successful metaphases and no changes by CC displayed no copy number changes by aCGH. The most frequent abnormality found by aCGH among these normal karyotype cases was the presence of 5q deletion (2%), while other chromosomes affected were 7, 8, 11, 12 and 20. All these abnormalities were confirmed by FISH.
Regarding the patients with unsuccessful cytogenetics, 72.7% of cases displayed a normal aCGH profile, while 27.3% showed at least one genomic imbalance The most frequent genomic aberrations were losses in 4q (6%), 5q (12%) and 7q (9%), and gain of chromosome 8 (6%). In addition, three of these cases showed a complex karyotype, showing more than 5 abnormalities.
The use of aCGH karyotyping in the diagnosis of MDS could be used as a complementary technique to conventional karyotyping in the evaluation of MDS patients. Mainly in patients with unsuccessful cytogenetics and those with normal karyotype and <20 good-quality metaphases evaluated.
Hernández:Celgene: Research Funding.
The purpose of this study was to verify whether stress worsens the clinical symptomatology perceived by patients with lupus erythematosus. Toward this end, we considered two types of stressors-daily ...stress and high-intensity stressful life events.
In 46 patients with systemic lupus erythematosus and 12 patients with chronic lupus discoid, we studied the stress they experienced daily for 6 months and their disease symptoms. During this period, we also analyzed the levels of C3 and C4 complements and anti-DNAn antibodies. The systemic lupus erythematosus activity (assessed by the Systemic Lupus Activity Measures) and cumulative organ damage (assessed by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were also analyzed.
We did not find that high-intensity stressful life events produced a worsening of the symptomatology of the disease. However, using a time-series analysis (Box-Jenkins), we found that a high percentage of lupus patients (74.1%) perceived a worsening in their clinical symptomatology due to the effects of daily stress. Of this 74.1%, 53.4% worsened the same day they suffered the perceived daily stress, and the remaining 20.7% experienced an increase in symptoms both the same day and the following day. Subsequent Mann-Whitney analyses showed that the patients who worsened for 2 days because of the effects of stress had greater lupus activity, as evaluated by their levels of C3, C4, and anti-DNAn.
Daily stress, and not stressful life events, worsened the clinical symptomatology perceived by lupus erythematosus patients. This increase extended at times to 2 days, and was associated with greater lupic activity.
OBJECTIVESTo analyze the clinical utility and economic impact of conventional transbronchial needle aspiration (TBNA) in patients with diagnosis of bronchogenic carcinoma (BC) and mediastinal ...lymphadenopathies in thoracic computed tomography (CT). To assess the predictive factors of valid aspirations.PATIENTS AND METHODSRetrospective observational study between 2006 and 2011 of all TBNA performed in patients with final diagnosis of BC and accessible hilar or mediastinal lymphadenopathies on thoracic CT.RESULTSWe performed TBNA on 267 lymphadenopathies of 192 patients. In 34.9% of patients, two or more lymph nodes were biopsied. Valid aspirations were obtained in 153 patients (79.7%) that were diagnostic in 124 (64.6%). Multivariate analysis showed that factors associated with valid or diagnostic results are the diameter of the lymph node and the number of lymph nodes explored. TBNA was the only endoscopic technique that provided the diagnosis of BC in 54 patients (28.1%). Staging mediastinoscopy was avoided in 67.6% of patients. The prevalence of mediastinal lymph node involvement was 74.4%, sensitivity of TBNA was 86.2% and negative predictive value was 63.6%. Including mediastinoscopy and other avoided diagnostic techniques, TBNA saved 451.57 € per patient.CONCLUSIONSTBNA is a clinically useful, cost-effective technique in patients with BC and mediastinal or hilar lymphadenopathies. It should therefore be performed on a regular basis during diagnostic bronchoscopy of these patients.
Purpose: To compare the prevalence of migraine headaches in the Romany population with the prevalence in the general Spanish population and to describe its association with demographic and clinical ...risk factors. Method: A cross-sectional study using data from the 2006 Spanish National Health Survey (n = 16,079) and the National Health Survey in the Romany Population (n = 993). Inclusion criteria were migraine headache diagnosed by a neurologist, suffered over the preceding 2 weeks that reduced work or leisure activity by half a day or more. Results: The prevalence of migraine in the Romany population (29.4%, 95% confidence interval CI = 26.48-32.53) was significantly higher than in the general Spanish population (12.52%, 95% CI = 11.85-13.22). Females (odds ratio OR = 1.56, 95% CI = 1.10-2.21), those ≤40 years old (OR = 4.17, 95% CI = 1.78-9.62), those sleeping ≤8 hours/day or less (OR = 1.85, 95% CI = 1.32-2.59), those with body mass index >30 kg/m2 (OR = 1.75, 95% CI = 1.15-2.65), those suffering from osteoarthritis (OR = 2.59, 95% CI = 1.54-4.36), and those suffering from allergy (OR = 1.69, CI = 1.05-2.71) were associated with higher incidence of migraines. Romanies with migraines reported worse self-perceived health status (OR = 2.11, 95% CI = 1.41-3.15) and higher incidence of depression (OR = 2.09 95% CI = 1.32-3.30) than those without. Discussion: Prevalence of migraines is greater in the Romany living in Spain than in the general Spanish population. Implication for practice: Public health systems should focus prevention campaigns specifically on this population and concentrate on those factors that are potentially modifiable.
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