Patients’ opinions about knowing their risk for depression and what to do about it: The PredictD-Qualitative study

Background: The predictD study developed and validated a risk algorithm for predicting the onset of major depression in primary care. We aimed to explore the opinion of patients about knowing their risk for depression and the values and criteria upon which these opinions are based. Methods: A maximum variation sample of patients was taken, stratified by city, age, gender, immigrant status, socioeconomic status and lifetime depression. The study participants were 52 patients belonging to 13 urban health centres in seven different cities around Spain. Seven Focus Groups (FGs) were given held with primary care patients, one for each of the seven participating cities. Results: The results showed that patients generally welcomed knowing their risk for depression. Furthermore, in light of available evidence several patients proposed potential changes in their lifestyles to prevent depression. Patients generally preferred to ask their General Practitioners (GPs) for advice, though mental health specialists were also mentioned. They suggested that GPs undertake interventions tailored to each patient, from a ‘‘patient-centred’’ approach, with certain communication skills, and giving advice to help patients cope with the knowledge that they are at risk of becoming depressed. Conclusions: Patients are pleased to be informed about their risk for depression. We detected certain beliefs, attitudes, values, expectations and behaviour among the patients that were potentially useful for future primary prevention programmes on depression.Junta de Andalucía 2008/0195Gobierno Vasco 2008/111021Spanish Network of Primary Care Research (redIAPP) RD06/0018Salud Mental, Servicios y Atención Primaria (SAMSERAP

Evaluation of the diagnostic accuracy of laboratory-based screening for hepatitis C in dried blood spot samples: A systematic review and meta-analysis

The dried blood spot (DBS) is increasingly used for the hepatitis C virus (HCV) screening. Our objective was to perform a meta-analysis of the methodology for HCV screening in DBS samples, particularly in the type of diagnostic assay used. We performed a meta-analysis of all eligible studies published to date (March 2018). The literature search revealed 26 studies: 21 for detection of anti-HCV antibodies and 10 for detection of HCV-RNA. Statistical analyses were performed using Meta-DiSc and STATA (MIDAS module). For detection of HCV antibodies, pooled diagnostic accuracy measures were as follows: sensitivity 96.1%, specificity 99.2%, positive likelihood ratio (PLR) 105, negative likelihood ratio (NLR) 0.04, diagnostic odds ratio (DOR) 2692.9, and summary receiver operating characteristic (SROC) 0.997 ± 0.001. For detection of HCV-RNA, the pooled diagnostic accuracy measures were as follows: sensitivity 97.8%, specificity 99.2%, PLR 44.8, NLR 0.04, DOR 1966.9, and SROC 0.996 ± 0.013. Similar values of pooled diagnostic accuracy measures were found according to the type of anti-HCV antibody detection assay (enzyme-linked immunosorbent assay, rapid diagnostic test, and chemiluminescence assays) and HCV-RNA detection assay (real-time polymerase chain reaction and transcription-mediated amplification). The analysis of external validity showed a high negative predicted value (NPV) for both approaches, but a low positive predicted value (PPV) when prevalence was < 10%, particularly in HCV-RNA tests. Finally, this meta-analysis is subject to limitations, especially publication bias and significant heterogeneity between studies. In conclusion, HCV screening in DBS samples has an outstanding diagnostic performance, with no relevant differences between the techniques used. However, external validity may be limited when the HCV prevalence is low.This study was supported by grants from Instituto de Salud Carlos III [grant numbers PI17CIII/00003 and RD16CIII/0002/0002], and a research grant from Merck Sharpe & Dohme (MISP IIS#54846). No funding bodies had any role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

A novel controlled drug-delivery system for growth hormone applied to healing skin wounds in diabetic rats

Controlled release systems for drugs, hormones and growth factors can be particularly useful in tissue repair processes. These systems act as a biodegradable support containing the substance to be delivered, allowing their gradual release. In the past years, the local application of growth factors has acquired special relevance as a therapeutic option for use in subjects who show de cient tissue scarring, the hormone dose being the limiting factor for its success. In this study, the in vitro biocompatibility of a copolymer formed by vinylpyrrolidone and 2-hydroxyethyl methacrylate, used as an administration vehicle for hGH, was evaluated. The system was then tested in vivo in terms of its capacity for healing incisional wounds in healthy and diabetic rats. For the in vitro studies, polymer and hormone degradation rates were determined, and polymer biocompatibility was evaluated in broblast cultures. In the in vivo experiments, an incision was made in the back of the animals, and polymers discs with/ without hGH, were introduced in the aperture. Morphological, immunohistochemical and morphometric evaluations were performed on wound tissue specimens 3¿10 days after surgery. In vitro, the polymer was found to be biodegradable and showed no toxic effects on broblasts, the hormone being slowly released to the culture medium. In untreated diabetic rats, a delayed skin scarring and cell response were observed, compared to that noted in healthy animals. Skin closure, keratinisationand brosis occurred earlier in the presence of the polymer-hGH system. The use of this co-polymer as an administrationvehicle for hGH improves the wound scarring process in the pathological setting of diabetes

Improving the interoperability between MPI and task-based programming models

In this paper we propose an API to pause and resume task execution depending on external events. We leverage this generic API to improve the interoperability between MPI synchronous communication primitives and tasks. When an MPI operation blocks, the task running is paused so that the runtime system can schedule a new task on the core that became idle. Once the MPI operation is completed, the paused task is put again on the runtime system's ready queue. We expose our proposal through a new MPI threading level which we implement through two approaches. The first approach is an MPI wrapper library that works with any MPI implementation by intercepting MPI synchronous calls, implementing them on top of their asynchronous counterparts. In this case, the task-based runtime system is also extended to periodically check for pending MPI operations and resume the corresponding tasks once MPI operations complete. The second approach consists in directly modifying the MPICH runtime system, a well-known implementation of MPI, to directly call the pause/resume API when a synchronous MPI operation blocks and completes, respectively. Our experiments reveal that this proposal not only simplifies the development of hybrid MPI+OpenMP applications that naturally overlap computation and communication phases; it also improves application performance and scalability by removing artificial dependencies across communication tasks.This work has been developed with the support of the European Union Horizon 2020 Programme through both the INTERTWinE project (agreement No. 671602) and the Marie Sk lodowska-Curie grant (agreement No. 749516); the Spanish Government through the Severo Ochoa Program (SEV-2015-0493); the Spanish Ministry of Science and Innovation (TIN2015-65316-P) and the Generalitat de Catalunya (2017-SGR-1414).Peer ReviewedPostprint (author's final draft

Effects of HCV Eradication on Bone mineral density in HIV/HCV Coinfected Patients

Little is known about the effects of eradication of HCV on bone mineral density (BMD) and biomarkers of bone remodeling in HIV/HCV coinfected patients. We prospectively assessed standardized BMD (sBMD) at the lumbar spine and femoral neck, World Health Organization (WHO) BMD categories at both sites, and plasma concentrations of soluble receptor activator of nuclear factor-kappaβ ligand (sRANKL), and osteoprotegerin (OPG) at baseline (the date of initiation of anti-HCV therapy) and at 96 weeks. A total of 238 patients were included, median age 49.5 years, 76.5% males, 48.3% with cirrhosis, 98.3% on antiretroviral therapy, median CD4+ cell count 527 cells/mm 3, 86.6% with HIV-1 RNA < 50 copies/mL. The prevalence of osteoporosis at baseline at the lumbar spine (LS) and femoral neck (FN) was 17.6% and 7.2%, respectively. Anti-HCV therapy comprised pegylated interferon and ribavirin (PegIFN-RBV) plus one direct-acting antiviral in 53.4%, PegIFN-RBV in 34.5%, and sofosbuvir/RBV in 12.2%. A total of 145 (60.9%) patients achieved sustained viral response (SVR). No significant effect of SVR was observed on sBMD for the interaction between time and SVR either in the LS (P=0.801) or the FN (P=0.911). Likewise, no significant effect of SVR was observed in plasma levels of sRANKL (P=0.205), OPG (P=0.249), and sRANKL/OPG ratio (P=0.123) for the interaction between time and SVR. No significant correlation was found between fibrosis by transient elastography, and LS and FN sBMD, at baseline, and week 96. SVR was not associated with significant changes in BMD nor biomarkers of bone remodeling in HIV/HCV-coinfected persons.This study was supported by Instituto de Salud Carlos III (ISCII), grant numbers PI11/01556, PI14/01094, PI14/01581, and PI14CIII/00011, and by Ministerio de Sanidad, Servicios Sociales e Igualdad, grant number EC11-241. The study was also funded by the RD16/0025/0017, RD16/0025/0018 and RD16CIII/0002/0002 projects as part of the Plan Nacional R + D + I and cofunded by ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER).S

European mitochondrial haplogroups predict liver-related outcomes in patients coinfected with HIV and HCV: a retrospective study

BACKGROUND: Mitochondrial DNA (mtDNA) haplogroups have been associated with advanced liver fibrosis and cirrhosis in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Our aim was to determine whether mtDNA haplogroups are associated with liver-related events (LREs) in HIV/HCV-coinfected patients. METHODS: We carried out a retrospective cohort study in HIV/HCV-coinfected patients who were potential candidates for therapy with interferon and ribavirin (IFN/Rib) between 2000 and 2009. The primary endpoint was the occurrence of LREs (decompensation or hepatocellular carcinoma). mtDNA genotyping was performed using the Sequenom MassARRAY platform. We used Fine and Gray proportional hazards model to test the association between mtDNA haplogroups and LREs, considering death as a competitive risk. RESULTS: The study population comprised 243 patients, of whom 40 had advanced fibrosis or cirrhosis. After a median follow-up of 7.7 years, 90 patients treated with IFN/Rib achieved sustained viral response (SVR), 18 patients had LREs, and 11 patients died. Patients with haplogroup H had lower cumulative incidence than patients with other haplogroups (p = 0.012). However, patients with haplogroup T had higher cumulative incidence than patients with other haplogroups (p = 0.074). In the multivariate analysis, haplogroup T was associated with an increased hazard of developing LREs [adjusted subhazard ratio (aSHR) = 3.56 (95% CI 1.13;11.30); p = 0.030]; whereas haplogroup H was not associated with lower hazard of LREs [aSHR = 0.36 (95% CI 0.10;1.25); p = 0.105]. When we excluded patients who achieved SVR during follow-up, we obtained similar SHR values. CONCLUSIONS: European mitochondrial haplogroups may influence the natural history of chronic hepatitis C.This study was supported by grants from Fondo de Investigación de Sanidad en España (Spanish Funds for Health Research [FIS]), grant numbers PI14/01094 and PI17/00657 to JB, PI14CIII/00011 and PI17CIII/00003 to SR. The study was also funded by the RD16CIII/0002/0002 and RD16/0025/0017 projects as part of the Plan Nacional R + D + I and cofunded by ISCIII- Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER). JB is an investigator from the Programa de Intensificación de la Actividad Investigadora en el Sistema Nacional de Salud (I3SNS), Refs INT15/00079 and INT16/00100. LMM, MAJS, and PGB are supported by “Instituto de Salud Carlos III” (grant numbers CD14/00002, CD13/00013, CP14/0010, and FI12/00036; respectively).S

Development and validation of a prediction model for 30-day mortality in hospitalised patients with COVID-19: the COVID-19 SEIMC score

Objective To develop and validate a prediction model of mortality in patients with COVID-19 attending hospital emergency rooms. Design Multivariable prognostic prediction model. Setting 127 Spanish hospitals. Participants Derivation (DC) and external validation (VC) cohorts were obtained from multicentre and single centre databases, including 4035 and 2126 patients with confirmed COVID-19, respectively. Interventions Prognostic variables were identified using multivariable logistic regression. Main outcome measures 30-day mortality. Results Patients? characteristics in the DC and VC were median age 70 and 61 years, male sex 61.0% and 47.9%, median time from onset of symptoms to admission 5 and 8 days, and 30-day mortality 26.6% and 15.5%, respectively. Age, low age-adjusted saturation of oxygen, neutrophil-to-lymphocyte ratio, estimated glomerular filtration rate by the Chronic Kidney Disease Epidemiology Collaboration (CKD EPI) equation, dyspnoea and sex were the strongest predictors of mortality. Calibration and discrimination were satisfactory with an area under the receiver operating characteristic curve with a 95% CI for prediction of 30-day mortality of 0.822 (0.806?0.837) in the DC and 0.845 (0.819?0.870) in the VC. A simplified score system ranging from 0 to 30 to predict 30-day mortality was also developed. The risk was considered to be low with 0?2 points (0%?2.1%), moderate with 3?5 (4.7%?6.3%), high with 6?8 (10.6%?19.5%) and very high with 9?30 (27.7%?100%). Conclusions A simple prediction score, based on readily available clinical and laboratory data, provides a useful tool to predict 30-day mortality probability with a high degree of accuracy among hospitalised patients with COVID-19.Funding. This work was supported by Fundación SEIMC/GeSIDA. The funders had no role in study design, data collection, data interpretation or writing of the manuscript. JB, JRB, IJ, JC, JP and JRA received funding for research from Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, cofinanced by the European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020. Spanish AIDS Research Network (RIS) (RD16/0025/0017 (JB), RD16/0025/0018 (JRA), RD16CIII/0002/0006 (IJ)). Spanish Network for Research in Infectious Diseases (REIPI) (RD16/0016/0001 (JRB), RD16/0016/0005 (JC) and RD16/0016/0009 (JP))

Evolution of adherence to antiretroviral treatment in a spanish hospital during 2001, 2005 and 2008

The aim of this study was to analyze the evolution of adherence to highly active antiretroviral therapy (HAART) in the Hospital General Universitario Gregorio Marañón (Madrid, Spain) over the last 8 years and determine the variables associated with the complexity of treatment and suboptimal adherence. An observational, retrospective method was used to measure adherence during the first 6 months of HAART in 3 cohorts: 2001 cohort (n = 90), 2005 cohort (n = 98), and 2008 cohort (n = 110). The adherence rate was determined using 2 methods: Pharmacy Department dispensation records and virologic response data. The evolution of the complexity of treatment and its influence on the adherence rate was analyzed by logistic regression. Adherence to HAART increased progressively from 45.6 % in 2001 to 56.1 % in 2005 and 77.3 % in 2008. Statistically significant differences were only observed between cohorts in 2005 and 2008. The average daily pill burden was 7, 4, and 4.5 tablets, respectively. The percentage of patients on twice-daily regimens decreased from 93.3 % in 2001 to 63.6 % in 2008, with a parallel increase in once-daily regimens. The proportion of patients with dietary restrictions decreased from 24.4 % to 3.6 %. A statistically significant association was found between the number of medication units per day and adherence and between frequency of administration and adherence. Adherence to HAART has improved significantly in the last 8 years. While the complexity of the treatment was significantly reduced in 2005, the largest increase in adherence occurred in the last cohort, which shows the influence of factors other than treatment simplification.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children: 3 years of follow-up. Long-term response to nelfinavir in children

BACKGROUND: Antiretroviral treatment (ART) in children has special features and consequently, results obtained from clinical trials with antiretroviral drugs in adults may not be representative of children. Nelfinavir (NFV) is an HIV-1 Protease Inhibitor (PI) which has become as one of the first choices of PI for ART in children. We studied during a 3-year follow-up period the effects of highly active antiretroviral therapy with nelfinavir in vertically HIV-1 infected children. METHODS: Forty-two vertically HIV-infected children on HAART with NFV were involved in a multicentre prospective study. The children were monitored at least every 3 months with physical examinations, and blood sample collection to measure viral load (VL) and CD4+ cell count. We performed a logistic regression analysis to determinate the odds ratio of baseline characteristics on therapeutic failure. RESULTS: Very important increase in CD4+ was observed and VL decreased quickly and it remained low during the follow-up study. Children with CD4+ <25% at baseline achieved CD4+ >25% at 9 months of follow-up. HIV-infected children who achieved undetectable viral load (uVL) were less than 40% in each visit during follow-up. Nevertheless, HIV-infected children with VL >5000 copies/ml were less than 50% during the follow-up study. Only baseline VL was an important factor to predict VL control during follow-up. Virological failure at defined end-point was confirmed in 30/42 patients. Along the whole of follow-up, 16/42 children stopped HAART with NFV. Baseline characteristics were not associated with therapeutic change. CONCLUSION: NFV is a safe drug with a good profile and able to achieve an adequate response in children