First month prednisone dose predicts prednisone burden during the following 11 months: An observational study from the RELES cohort

Aim: To study the influence of prednisone dose during the first month after systemic lupus erythematosus (SLE) diagnosis (prednisone-1) on glucocorticoid burden during the subsequent 11 months (prednisone-2–12). Methods: 223 patients from the Registro Español de Lupus Eritematoso Sistémico inception cohort were studied. The cumulative dose of prednisone-1 and prednisone-2–12 were calculated and recoded into a four-level categorical variable: no prednisone, low dose (up to 7.5 mg/day), medium dose (up to 30 mg/day) and high dose (over 30 mg/day). The association between the cumulative prednisone-1 and prednisone-2–12 doses was tested. We analysed whether the four-level prednisone-1 categorical variable was an independent predictor of an average dose >7.5 mg/day of prednisone-2–12. Adjusting variables included age, immunosuppressives, antimalarials, methyl-prednisolone pulses, lupus nephritis and baseline SLE Disease Activity Index (SLEDAI). Results: Within the first month, 113 patients (51%) did not receive any prednisone, 24 patients (11%) received average low doses, 46 patients (21%) received medium doses and 40 patients (18%) received high doses. There was a strong association between prednisone-1 and prednisone-2–12 dose categories (p7.5 mg/day, while patients receiving low-dose prednisone-1 were not (adjusted OR 1.4, 95% CI 0. 0.38 to 5.2). If the analysis was restricted to the 158 patients with a baseline SLEDAI of =6, the model did not change. Conclusion: The dose of prednisone during the first month after the diagnosis of SLE is an independent predictor of prednisone burden during the following 11 months

Modifications in host cell cytoskeleton structure and function mediated by intracellular HIV-1 Tat protein are greatly dependent on the second coding exon

Supplementary Data are available at NAR OnlineThe human immunodeficiency virus type 1 (HIV-1) regulator Tat is essential for viral replication because it achieves complete elongation of viral transcripts. Tat can be released to the extracellular space and taken up by adjacent cells, exerting profound cytoskeleton rearrangements that lead to apoptosis. In contrast, intracellular Tat has been described as protector from apoptosis. Tat gene is composed by two coding exons that yield a protein of 101 amino acids (aa). First exon (1–72aa) is sufficient for viral transcript elongation and second exon (73–101 aa) appears to contribute to non-transcriptional functions. We observed that Jurkat cells stably expressing intracellular Tat101 showed gene expression deregulation 4-fold higher than cells expressing Tat72. Functional experiments were performed to evaluate the effect of this deregulation. First, NF-iB-, NF-AT- and Sp1-dependent transcriptional activities were greatly enhanced in Jurkat-Tat101, whereas Tat72 induced milder but efficient activation. Second, cytoskeleton-related functions as cell morphology, proliferation, chemotaxis, polarization and actin polymerization were deeply altered in Jurkat- Tat101, but not in Jurkat-Tat72. Finally, expression of several cell surface receptors was dramatically impaired by intracellular Tat101 but not by Tat72. Consequently, these modifications were greatly dependent on Tat second exon and they could be related to the anergy observed in HIV-1-infected T cells.Plan Nacional del SIDA (MVI 1434/05–5), FIPSE 36584/ 06 and 36633/07, VIRHORST Network from Comunidad de Madrid (Spain), FIS PI040614 and PI0808752, ISCIII-RETIC RD06/0006, EUROPRISE Network of Excellence of the EU (Grant no. LSHP CT-2006- 037611), and BIO2008-04384 from the Ministerio de Ciencia e Innovacio´ n, Espan˜ a. Funding for open access charge: Instituto de Salud Carlos III, Ministry of Science and Technology, Spain.Peer reviewe

External validation of multidimensional prognostic indices (ADO, BODEx and DOSE) in a primary care international cohort (PROEPOC/COPD cohort)

Background: Due to the heterogeneous and systemic nature of the chronic obstructive pulmonary disease (COPD), the new guidelines are oriented toward individualized attention. Multidimensional scales could facilitate its proper clinical and prognostic assessment, but not all of them were validated in an international primary care cohort, different from the original ones used for model development. Therefore, our main aim is to assess the prognostic capacity of the ADO, BODEx and DOSE indices in primary care for predicting mortality in COPD patients and to validate the models obtained in subgroups of patients, classified by revised Global Initiative for Chronic Obstructive Lung Disease (2011) and updated Spanish Guideline (2014). Besides, we want to confirm that the prognostic capacity of all indices increases if the number of exacerbations is substituted by the interval between them and to assess the impact on health of the patient''s lifestyle, social network and adherence to treatment. Methods: Design: External validation of scales, open and prospective cohort study in primary care. Setting: 36 health centres in 6 European high, medium and low income countries. Subjects: 477 patients diagnosed with COPD, captured in clinical visit by their General Practitioner/Nurse. Predictors: Detailed patient history, exacerbations, lung function test and questionnaires at baseline. Outcomes: Exacerbations, all-cause mortality and specific mortality, within 5 years of recruitment. Analysis: Multivariate logistic regression and Cox regression will be used. Possible non-linear effect of the indices will be studied by using Structured Additive Regression models with penalised splines. Subsequently, we will assess different aspects of the regression models: discrimination, calibration and diagnostic precision. Clinical variables modulated in primary care and the interval between exacerbations will be considered and incorporated into the analysis. Discussion: The Research Agenda for General Practice/Family Medicine highlights that the evidence on predictive values of prognostic indices in primary care is scarce. A prospective cohort like that of PROEPOC/COPD provides good opportunities for research into COPD and make communication easier between family practitioners, nursing staff, pneumologists and other professionals, supporting a multi-disciplinary approach to the treatment of these patients. Trial registration:ISRCTN52402811. Date: 15/01/2015. Prospectively registered

Measurement of Upper Limb Range of Motion Using Wearable Sensors: A Systematic Review.

Background: Wearable sensors are portable measurement tools that are becoming increasingly popular for the measurement of joint angle in the upper limb. With many brands emerging on the market, each with variations in hardware and protocols, evidence to inform selection and application is needed. Therefore, the objectives of this review were related to the use of wearable sensors to calculate upper limb joint angle. We aimed to describe (i) the characteristics of commercial and custom wearable sensors, (ii) the populations for whom researchers have adopted wearable sensors, and (iii) their established psychometric properties. Methods: A systematic review of literature was undertaken using the following data bases: MEDLINE, EMBASE, CINAHL, Web of Science, SPORTDiscus, IEEE, and Scopus. Studies were eligible if they met the following criteria: (i) involved humans and/or robotic devices, (ii) involved the application or simulation of wearable sensors on the upper limb, and (iii) calculated a joint angle. Results: Of 2191 records identified, 66 met the inclusion criteria. Eight studies compared wearable sensors to a robotic device and 22 studies compared to a motion analysis system. Commercial (n = 13) and custom (n = 7) wearable sensors were identified, each with variations in placement, calibration methods, and fusion algorithms, which were demonstrated to influence accuracy. Conclusion: Wearable sensors have potential as viable instruments for measurement of joint angle in the upper limb during active movement. Currently, customised application (i.e. calibration and angle calculation methods) is required to achieve sufficient accuracy (error < 5°). Additional research and standardisation is required to guide clinical application

Diagnostic accuracy of a clinical diagnosis of idiopathic pulmonary fibrosis: An international case-cohort study

We conducted an international study of idiopathic pulmonary fibrosis (IPF) diagnosis among a large group of physicians and compared their diagnostic performance to a panel of IPF experts. A total of 1141 respiratory physicians and 34 IPF experts participated. Participants evaluated 60 cases of interstitial lung disease (ILD) without interdisciplinary consultation. Diagnostic agreement was measured using the weighted kappa coefficient (\u3baw). Prognostic discrimination between IPF and other ILDs was used to validate diagnostic accuracy for first-choice diagnoses of IPF and were compared using the Cindex. A total of 404 physicians completed the study. Agreement for IPF diagnosis was higher among expert physicians (\u3baw=0.65, IQR 0.53-0.72, p20 years of experience (C-index=0.72, IQR 0.0-0.73, p=0.229) and non-university hospital physicians with more than 20 years of experience, attending weekly MDT meetings (C-index=0.72, IQR 0.70-0.72, p=0.052), did not differ significantly (p=0.229 and p=0.052 respectively) from the expert panel (C-index=0.74 IQR 0.72-0.75). Experienced respiratory physicians at university-based institutions diagnose IPF with similar prognostic accuracy to IPF experts. Regular MDT meeting attendance improves the prognostic accuracy of experienced non-university practitioners to levels achieved by IPF experts

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Dosis bajas de haloperidol en combinación con ondansetrón no son eficaces para la profilaxis de náuseas y vómitos postoperatorios en pacientes propicios a esta complicación

Introducción El objetivo de este estudio fue evaluar la eficacia y los efectos secundarios de distintas combinaciones de antieméticos para la profilaxis de náuseas y vómitos postoperatorios (NVPO) en pacientes propicios a presentarlos tras cirugía muy emetógena. Métodos Tras revisar retrospectivamente las historias clínicas de pacientes sometidos a cirugía electiva muy emetógena bajo anestesia general durante el periodo 2009 a 2011, seleccionamos 368 mujeres con puntuación de Apfel ≥3 y que recibieron una combinación de 2 antieméticos como profilaxis. Analizamos la incidencia de NVPO a las 2, 6, 12 y 24 h del postoperatorio, rescates antieméticos, patrón de aparición de NVPO, efectos secundarios y nivel de sedación. Valoramos la respuesta completa como ausencia de NVPO en las primeras 24 h. Resultados Ondansetrón 4 mg i.v. en combinación con dexametasona 8 mg i.v. (O&Dex), haloperidol 1 mg i.v. (O&Hal1), haloperidol 2 mg i.v. (O&Hal2) o droperidol 1,25 mg i.v. (O&Dro) fueron las combinaciones más empleadas. La respuesta completa fue mayor en los grupos O&Dex: 68,5% (IC: 58-78); O&Hal2: 64,1% (IC: 53-74) y O&Dro 63% (IC: 52-73) que en el grupo O&Hal1: 41,3% (IC: 31-52) (p < 0,01). La máxima incidencia de NVPO ocurrió entre las 2 y 6 h del postoperatorio. La incidencia de efectos secundarios fue mayor en el grupo O&Hal2. Conclusiones En pacientes con elevado riesgo de NVPO sometidos a cirugía muy emetógena, la eficacia de dosis bajas de haloperidol (1 mg) en combinación con ondansetrón es escasa. Dosis mayores (2 mg) son altamente eficaces, pero se asocian a una alta incidencia de efectos secundarios.Background In this observational study we reviewed the efficacy and side effects of different antiemetic combinations used in our hospital for postoperative nausea and vomiting (PONV) prophylaxis in high-risk women undergoing highly emetogenic surgery. Methods After reviewing retrospectively the medical records of patients undergoing highly emetogenic elective surgeries under general anaesthesia, we selected 368 women whose Apfel risk score was ≥ 3 and receiving a combination of 2 antiemetics for PONV prophylaxis. We analysed the incidence of PONV at 2, 6, 12 and 24 h after surgery, antiemetic rescue requirements, pattern of occurrence of PONV, side effects and level of sedation were also assessed. The main goal was complete response defined as no PONV within 24 h after surgery. Results Ondansetron 4 mg i.v. plus dexamethasone 8 mg i.v. (O&Dex), haloperidol 1 mg i.v. (O&Hal1), haloperidol 2 mg i.v. (O&Hal2) or droperidol 1.25 mg i.v. (O&Dro) were the combinations most frequently used. The complete response was better in groups O&Dex: 68.5% (CI: 58-78), O&Hal2: 64.1% (CI: 53-74) and O&Dro 63% (CI: 52-73) than in group O&Hal1: 41.3% (CI: 31-52) (p < 0,01). Peak incidence of PONV occurred within the 2-6 h period. The incidence of side effects was higher in group O&Hal2. Conclusion In high risk patients for PONV who underwent highly emetogenic surgeries, the efficacy of low-dose haloperidol (1 mg) in combination is limited. Higher doses (2 mg) are more effective but its use is associated with a high incidence of side effects