Switching from a protease inhibitor-based regimen to a dolutegravir-based regimen : a randomized clinical trial to determine the effect on peripheral blood and ileum biopsies from antiretroviral therapy-suppressed human immunodeficiency virus-infected individuals

Background: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Methods: Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. Results: There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4(+) T cells in both groups (P <.01). Residual viremia in plasma decreased in the switch group (P =.03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. Conclusions: The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4(+) T cells

Effectiveness of a multidisciplinary BIOPSYCHOSOCIAL intervention for non-specific SUBACUTE low back pain in a working population : a cluster randomized clinical trial

BACKGROUND: Low back pain (LBP) is a multifactorial condition with individual and societal impact that affects populations globally. Current guidelines for the treatment of LBP recommend pharmacological and non-pharmacological strategies. The aim of this study was to compare usual clinical practice with the effectiveness of a biopsychosocial multidisciplinary intervention in reducing disability, severity of pain and improving quality of life in a working population of patients with subacute (2-12 weeks), non-specific LBP. METHODS: Longitudinal cluster randomized clinical trial conducted in 39 Primary Health Care Centres (PHCC) of Barcelona, with patients aged 18-65 years (n = 501; control group = 239; 26 PHCC, intervention group = 262; 13 PHCC). The control group received usual clinical care. The intervention group received usual clinical care plus a biopsychosocial multidisciplinary intervention, which consisted of physiotherapy, cognitive-behavioural therapy and medication. The main outcomes were changes in the Roland Morris Disability Questionnaire (RMDQ), and the minimal clinically important differences. Secondary outcomes were changes in the McGill Pain (MGPQ) and Quality of Life (SF-12) questionnaires. Assessment was conducted at baseline, 3 and 12 months. Analysis was by intention-to-treat and analyst-blinded. Multiple imputations were used. RESULTS: Of the 501 enrolled patients, 421 (84%) provided data at 3 months, and 387 (77.2%) at 12 months. Mean age was 46.8 years (SD: 11.5) and 64.7% were women. In the adjusted analysis of the RMDQ outcome, only the intervention group showed significant changes at 3 months (- 1.33 points, p = 0.005) and at 12 months (- 1.11 points, p = 0.027), but minimal clinically important difference were detected in both groups. In the adjusted analysis of the RMDQ outcome, the intervention group improvement more than the control group at 3 months (- 1.33 points, p = 0.005) and at 12 months (- 1.11 points, p = 0.027). The intervention group presented a significant difference. Both groups presented a minimal clinically important difference, but more difference in the intervention group. The intervention group presented significant differences in the MGPQ scales of current pain intensity and VAS scores at 3 months. No statistically significant differences were found in the physical and mental domains of the SF-12. CONCLUSIONS: A multidisciplinary biopsychosocial intervention in a working population with non-specific subacute LBP has a small positive impact on disability, and on the level of pain, mainly at short-term, but no difference on quality of life. TRIAL REGISTRATION: ISRCTN21392091 (17 oct 2018) (Prospectively registred

Differences in Adipose Tissue and Lean Mass Distribution in Patients with Collagen VI Related Myopathies Are Associated with Disease Severity and Physical Ability

Mutations in human collagen VI genes cause a spectrum of musculoskeletal conditions in children and adults collectively termed collagen VI-related myopathies (COL6-RM) characterized by a varying degree of muscle weakness and joint contractures and which include Ullrich Congenital Muscular Dystrophy (UCMD) and Bethlem Myopathy (BM). Given that collagen VI is one of the most abundant extracellular matrix proteins in adipose tissue and its emerging role in energy metabolism we hypothesized that collagen VI deficiency might be associated with alterations in adipose tissue distribution and adipokines serum profile. We analyzed body composition by means of dual-energy X-ray absorptiometry in 30 pediatric and adult COL6-RM myopathy patients representing a range of severities (UCMD, intermediate-COL6-RM, and BM). We found a distinctive pattern of regional adipose tissue accumulation which was more evident in children at the most severe end of the spectrum. In particular, the accumulation of fat in the android region was a distinguishing feature of UCMD patients. In parallel, there was a decrease in lean mass compatible with a state of sarcopenia, particularly in ambulant children with an intermediate phenotype. All children and adult patients that were sarcopenic were also obese. These changes were significantly more pronounced in children with collagen VI deficiency than in children with Duchenne Muscular Dystrophy of the same ambulatory status. High molecular weight adiponectin and leptin were significantly increased in sera from children in the intermediate and BM group. Correlation analysis showed that the parameters of fat mass were negatively associated with motor function according to several validated outcome measures. In contrast, lean mass parameters correlated positively with physical performance and quality of life. Leptin and adiponectin circulating levels correlated positively with fat mass parameters and negatively with lean mass and thus may be relevant to the disease pathogenesis and as circulating markers. Taken together our results indicate that COL6-RM are characterized by specific changes in total fat mass and distribution which associate with disease severity, motor function, and quality of life and which are clinically meaningful and thus should be taken into consideration in the management of these patients

Switching From a Protease Inhibitor-based Regimen to a Dolutegravir-based Regimen : A Randomized Clinical Trial to Determine the Effect on Peripheral Blood and Ileum Biopsies From Antiretroviral Therapy-suppressed Human Immunodeficiency Virus-infected Individuals

Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4 + T cells in both groups (P <.01). Residual viremia in plasma decreased in the switch group (P =.03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4 + T cells. EudraCT 2014-004331-39. INDOOR evaluated the effect of switching from boosted protease inhibitor- to dolutegravir-based antiretroviral therapy on the HIV reservoir in peripheral blood and ileum. Residual plasma viremia and soluble CD14 levels decreased, but low-level HIV replication, the HIV reservoir, and immune activation remained unaffected

Pla estratègic d'atenció geriàtrica i pal·liativa especialitzada de Catalunya: línies estratègiques, projectes i actuacions

Pla estratègic; Atenció pal·liativa; Atenció centrada en la personaPlan estratégico; Atención paliativa; Atención centrada en la personaStrategic plan; Palliative care; Person centered careAquest document conté les línies estratègiques, projectes i actuacions del Pla estratègic d'atenció geriàtrica i pal·liativa especialitzada de Catalunya

De com i per què biblioteca s’escriu en femení. Segona part

The paper describes the social evolution of women, from their confinement at home to their active participation in public life, and the current tendencies of integration and equality of opportunities in all social aspects. The article is divided into two parts. First we study the role of women in librarian science in Catalonia and the history of their participation in the profession. The second part explains and evaluates the reasons of the feminization of librarian tasks

Enhancing butanol production by Clostridium beijerinckii through cathodic electrofermentation approach

Biobutanol, produced by solventogenic bacteria like Clostridium beijerinckii through acetone, butanol, and ethanol (ABE) fermentation, is a promising green alternative to fossil fuels. However, this ABE fermentation suffers drawbacks, such as a relatively low productivity that limits its industrial deployment. Electro-fermentation (EF) can modify the intracellular ratio of oxidized nicotinamide adenine dinucleotide to reduced nicotinamide (NAD+/NADH), a critical factor for butanol synthesis by C. beijerinckii, thus allowing higher product titers (or productivity) to be reached. RESULTS: The present study focuses on glucose-based ABE-EF at laboratory-scale. Three replicate EF reactors (300 mL) were constructed and used to grow C. beijerinckii. Different cathode materials were electrochemically characterized and tested. The effect of voltage application on process productivity was assessed by performing chronoamperometry tests at constant cathode potential (Ecat), ranging from −0,7 to −1,0 V vs Ag/AgCl. These trials were compared with a benchmark ABE fermentation that was performed without voltage application. Poising Ecat at −0,8 V vs Ag/AgCl resulted in the optimal EF scenario. In these conditions, the specific growth rate of bacteria was 73% higher than the benchmark ABE fermentation, with a productivity of 125,6 mg-butanol/L/h, a process yield of 0,15 g-butanol/g-glucose, and a selectivity for butanol of 87% (34%, 25%, and 11% higher than the benchmark fermentation, respectively). The addition of 0,5 mM neutral red as redox mediator in the broth led to a further improvement of butanol productivity (152,9 mg L h−1), requiring a very low energy consumption of 0,02 kWh/kg-butanol to run the EF process. CONCLUSION: Applying EF enhances the ABE fermentation in terms of butanol production, selectivity, and energy consumption

Economic evaluation of treatments for patients with localized prostate cancer in Europe : a systematic review

We would like to thank Aurea Martin for her writing assistance, proofreading, manuscript editing and the submission preparation process. Financial support for this study was provided by Instituto de Salud Carlos III FEDER: Fondo Europeo de Desarrollo Regional (FIS PI08/90090 and PI13/00412); Agència d'Informació, Avaluació i Qualitat en Salut (AIAQS), 436/05/2008; Ministerio de Ciencia e Innovación (PTAT2011-04891); and DIUE of Generalitat de Catalunya (2014 SGR 748). The funding agreements ensure the authors' independence in designing the study, interpreting the data, and writing and publishing the report.Background: Our objective was to assess the efficiency of treatments in patients with localized prostate cancer, by synthesizing available evidence from European economic evaluations through systematic review. Methods: Articles published 2000-2015 were searched in MEDLINE, EMBASE and NHS EED (Prospero protocol CRD42015022063). Two authors independently selected studies for inclusion and extracted the data. A third reviewer resolved discrepancies. We included European economic evaluations or cost comparison studies, of any modality of surgery or radiotherapy treatments, regardless the comparator/s. Drummond's Checklist was used for quality assessment. Results: After reviewing 8,789 titles, 13 European eligible studies were included: eight cost-utility, two cost-effectiveness, one cost-minimization, and two cost-comparison analyses. Of them, five compared interventions with expectant management, four contrasted robotic with non robotic-assisted surgery, three assessed new modalities of radiotherapy, and three compared radical prostatectomy with brachytherapy. All but two studies scored ≥8 in the quality checklist. Considering scenario and comparator, three interventions were qualified as dominant strategies (active surveillance, robotic-assisted surgery and IMRT), and six were cost-effective (radical prostatectomy, robotic-assisted surgery, IMRT, proton therapy, brachytherapy, and 3DCRT). However, QALY gains in most of them were small. For interventions considered as dominant strategies, QALY gain was 0.013 for active surveillance over radical prostatectomy; and 0.007 for robotic-assisted over non-robotic techniques. The highest QALY gains were 0.57-0.86 for radical prostatectomy vs watchful waiting, and 0.72 for brachytherapy vs conventional radiotherapy. Conclusions: Currently, relevant treatment alternatives for localized prostate cancer are scarcely evaluated in Europe. Very limited available evidence supports the cost-effectiveness of radical prostatectomy over watchful waiting, brachytherapy over radical prostatectomy, and new treatment modalities over traditional procedures. Relevant disparities were detected among studies, mainly based on effectiveness. These apparently contradictory results may be reflecting the difficulty of interpreting small differences between treatments regarding QALY gains

Rationale and methods of the MOVI-da10! Study –a cluster-randomized controlled trial of the impact of classroom-based physical activity programs on children’s adiposity, cognition and motor competence

Abstract Background Although physical activity (PA) integrated in schools’ classrooms have shown a positive effect on children’s behaviors, its effectiveness on cognitive functions, PA levels and other health variables remains unclear. This article outlines the rationale and methods of two classroom-based PA interventions (MOVI-da10!) on improving adiposity, executive function and motor competence in preschool children. Methods A three-arm cluster-randomized controlled trial (RCT) was carried out including eight schools (rural and urban areas) from Cuenca province, Spain. The schools were allocated to one of three groups: MOVI-da10-Enriched! intervention (n = 3), MOVI-da10-Standard! intervention, (n = 2), and the control group (n = 3). Around 900 children aged 4 to 6 years old were assesed at baseline (September 2017) and at the end (June 2018) of the intervention. The primary outcomes were changes in body fat by bioimpedance, executive function and motor competence. During a school year (from October 2017 to May 2018), children belonging to the MOVI-da10-Enriched! group performed enriched PA integrated into the academic curriculum including two active breaks lasting 10 min, 5 days/week. The children belonging to the MOVI-da10-Standard! group performed PA breaks (with low cognitive demand, where curricular contents were not reinforced) including two active breaks lasting 10 min, 5 days/week. In the control group, regular PA continued. Discussion To our knowledge, MOVI-da10! is the first RCT to examine the effectiveness of two programs (enriched PA integrated into the academic curriculum and PA breaks only) versus a control group on improving adiposity, executive function and motor competence in preschool children. Trial registration NCT03236363 (clinicaltrials.gov), 31st July 2017

Muscle MRI in a large cohort of patients with oculopharyngeal muscular dystrophy

© Author(s) (or their employer(s)) 2019.Background and objective Oculopharyngeal muscular dystrophy (OPMD) is a genetic disorder caused by an abnormal expansion of GCN triplets within the PABPN1 gene. Previous descriptions have focused on lower limb muscles in small cohorts of patients with OPMD, but larger imaging studies have not been performed. Previous imaging studies have been too small to be able to correlate imaging findings to genetic and clinical data. Methods We present cross-sectional, T1-weighted muscle MRI and CT-scan data from 168 patients with genetically confirmed OPMD. We have analysed the pattern of muscle involvement in the disease using hierarchical analysis and presented it as heatmaps. Results of the scans were correlated with genetic and clinical data. Results Fatty replacement was identified in 96.7% of all symptomatic patients. The tongue, the adductor magnus and the soleus were the most commonly affected muscles. Muscle pathology on MRI correlated positively