Multiple pre- and postzygotic components of reproductive isolation between two co-occurring Lysimachia species.

Genetic divergence between species depends on reproductive isolation (RI) due to traits that reduce interspecific mating (prezygotic isolation) or are due to reduced hybrid fitness (postzygotic isolation). Previous research found that prezygotic barriers tend to be stronger than postzygotic barriers, but most studies are based on the evaluation of F1 hybrid fitness in early life cycle stages. We combined field and experimental data to determine the strength of 17 prezygotic and postzygotic reproductive barriers between two Lysimachia species that often co-occur and share pollinators. We assessed postzygotic barriers up to F2 hybrids and backcrosses. The two species showed near complete RI due to the cumulative effect of multiple barriers, with an uneven and asymmetric contribution to isolation. In allopatry, prezygotic barriers contributed more to reduce gene flow than postzygotic barriers, but their contributions were more similar in sympatry. The strength of postzygotic RI was up to three times lower for F1 progeny than for F2 or backcrossed progenies, and RI was only complete when late F1 stages and either F2 or backcrosses were accounted for. Our results thus suggest that the relative strength of postzygotic RI may be underestimated when its effects on late stages of the life cycle are disregarded.

Integrative development of a short screening questionnaire of highly processed food consumption (sQ-HPF).

BACKGROUND: Recent lifestyle changes include increased consumption of highly processed foods (HPF), which has been associated with an increased risk of non-communicable diseases (NCDs). However, nutritional information relies on the estimation of HPF consumption from food-frequency questionnaires (FFQ) that are not explicitly developed for this purpose. We aimed to develop a short screening questionnaire of HPF consumption (sQ-HPF) that integrates criteria from the existing food classification systems. METHODS: Data from 4400 participants (48.1% female and 51.9% male, 64.9 ± 4.9 years) of the Spanish PREDIMED-Plus ("PREvention with MEDiterranean DIet") trial were used for this analysis. Items from the FFQ were classified according to four main food processing-based classification systems (NOVA, IARC, IFIC and UNC). Participants were classified into tertiles of HPF consumption according to each system. Using binomial logistic regression, food groups associated with agreement in the highest tertile for at least two classification systems were chosen as items for the questionnaire. ROC analysis was used to determine cut-off points for the frequency of consumption of each item, from which a score was calculated. Internal consistency of the questionnaire was assessed through exploratory factor analysis (EFA) and Cronbach's analysis, and agreement with the four classifications was assessed with weighted kappa coefficients. RESULTS: Regression analysis identified 14 food groups (items) associated with high HPF consumption for at least two classification systems. EFA showed that items were representative contributors of a single underlying factor, the "HPF dietary pattern" (factor loadings around 0.2). We constructed a questionnaire asking about the frequency of consumption of those items. The threshold frequency of consumption was selected using ROC analysis. Comparison of the four classification systems and the sQ-HPF showed a fair to high agreement. Significant changes in lifestyle characteristics were detected across tertiles of the sQ-HPF score. Longitudinal changes in HPF consumption were also detected by the sQ-HPF, concordantly with existing classification systems. CONCLUSIONS: We developed a practical tool to measure HPF consumption, the sQ-HPF. This may be a valuable instrument to study its relationship with NCDs. TRIAL REGISTRATION: Retrospectively registered at the International Standard Randomized Controlled Trial Registry ( ISRCTN89898870 ) on July 24, 2014.

Pro-vegetarian food patterns and cardiometabolic risk in the PREDIMED-Plus study: a cross-sectional baseline analysis.

PURPOSE: We explored the cross-sectional association between the adherence to three different provegetarian (PVG) food patterns defined as general (gPVG), healthful (hPVG) and unhealthful (uPVG), and the cardiometabolic risk in adults with metabolic syndrome (MetS) of the PREDIMED-Plus randomized intervention study. METHODS: We performed a cross-sectional analysis of baseline data from 6439 participants of the PREDIMED-Plus randomized intervention study. The gPVG food pattern was built by positively scoring plant foods (vegetables/fruits/legumes/grains/potatoes/nuts/olive oil) and negatively scoring, animal foods (meat and meat products/animal fats/eggs/fish and seafood/dairy products). The hPVG and uPVG were generated from the gPVG by adding four new food groups (tea and coffee/fruit juices/sugar-sweetened beverages/sweets and desserts), splitting grains and potatoes and scoring them differently. Multivariable-adjusted robust linear regression using MM-type estimator was used to assess the association between PVG food patterns and the standardized Metabolic Syndrome score (MetS z-score), a composed index that has been previously used to ascertain the cardiometabolic risk, adjusting for potential confounders. RESULTS: A higher adherence to the gPVG and hPVG was associated with lower cardiometabolic risk in multivariable models. The regression coefficients for 5th vs. 1st quintile were - 0.16 (95% CI: - 0.33 to 0.01) for gPVG (p trend: 0.015), and - 0.23 (95% CI: - 0.41 to - 0.05) for hPVG (p trend: 0.016). In contrast, a higher adherence to the uPVG was associated with higher cardiometabolic risk, 0.21 (95% CI: 0.04 to 0.38) (p trend: 0.019). CONCLUSION: Higher adherence to gPVG and hPVG food patterns was generally associated with lower cardiovascular risk, whereas higher adherence to uPVG was associated to higher cardiovascular risk.

The influence of symptom severity of palliative care patients on their family caregivers.

BACKGROUND: This study anlyzed whether family caregivers of patients with advanced cancer suffer impaired sleep quality, increased strain, reduced quality of life or increased care burden due to the presence and heightened intensity of symptoms in the person being cared for. METHOD: A total of 41 patient-caregiver dyads (41 caregivers and 41 patients with advanced cancer) were recruited at six primary care centres in this cross-sectional study. Data were obtained over a seven-month period. Caregiver's quality of sleep (Pittsburgh Sleep Quality Index), caregiver's quality of life (Quality of Life Family Version), caregiver strain (Caregiver Strain Index), patients' symptoms and their intensity (Edmonton Symptom Assessment System), and sociodemographic, clinical and care-related data variables were assessed. The associations were determined using non-parametric Spearman correlation. RESULTS: Total Edmonton Symptom Assessment System was significantly related to overall score of the Pittsburgh Sleep Quality Index (r = 0.365, p = 0.028), the Caregiver Strain Index (r = 0.45, p = 0.005) and total Quality of Life Family Version (r = 0.432, p = 0.009), but not to the duration of daily care (r = -0.152, p = 0.377). CONCLUSIONS: Family caregivers for patients with advanced cancer suffer negative consequences from the presence and intensity of these patients' symptoms. Therefore, optimising the control of symptoms would benefit not only the patients but also their caregivers. Thus, interventions should be designed to improve the outcomes of patient-caregiver dyads in such cases.

Hybrid Cements with ZnO Additions: Hydration, Compressive Strength and Microstructure.

The effect of ZnO has already been studied for Portland cement, but the study of its impact on hybrid pastes is scarce. Thus, in this investigation, the influence of ZnO addition on hydration, compressive strength, microstructure, and structure of hybrid pastes is presented. The analyses were made by setting time tests, compressive strength tests, X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis with differential scanning calorimetry, and scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. The results indicate that the setting time of the cements was delayed up to 39 min with additions of 3 wt% ZnO. Alternatively, the higher values of compressive strength were observed when 0.5 wt% ZnO was added to the cements for all curing days. In addition, no important differences in the microstructure of samples with different additions of ZnO were observed after 28 days of curing. It is expected that the use of ZnO contributes to the delay of the setting time and the increase of the compressive strength without negatively modifying the microstructure of hybrid pastes.

Development of a predictive inpatient falls risk model using machine learning.

AIM: The aims of this study were to create a model that detects the population at risk of falls taking into account a fall prevention variable and to know the effect on the model's performance when not considering it. BACKGROUND: Traditionally, instruments for detecting fall risk are based on risk factors, not mitigating factors. Machine learning, which allows working with a wider range of variables, could improve patient risk identification. METHODS: The sample was composed of adult patients admitted to the Internal Medicine service (total, n = 22,515; training, n = 11,134; validation, n = 11,381). A retrospective cohort design was used and we applied machine learning technics. Variables were extracted from electronic medical records electronic medical records. RESULTS: The Two-Class Bayes Point Machine algorithm was selected. Model-A (with a fall prevention variable) obtained better results than Model-B (without it) in sensitivity (0.74 vs. 0.71), specificity (0.82 vs. 0.74), and AUC (0.82 vs. 0.78). CONCLUSIONS: Fall prevention was a key variable. The model that included it detected the risk of falls better than the model without it. IMPLICATIONS FOR NURSING MANAGEMENT: We created a decision-making support tool that helps nurses to identify patients at risk of falling. When it is integrated in the electronic medical records, it decreases nurses' workloads by not having to collect information manually.

Pentaminomycins F and G, Nonribosomal Peptides Containing 2-Pyridylalanine.

Pentaminomycins F-H (1-3), a group of three new hydroxyarginine-containing cyclic pentapeptides, were isolated from cultures of a Streptomyces cacaoi subsp. cacaoi strain along with the known pentaminomycins A-E. The structures of the new peptides were determined by a combination of mass spectrometry, NMR, and Marfey's analyses. Pentaminomycins F (1) and G (2) were shown to contain the rare amino acid 3-(2-pyridyl)-alanine. This finding represents the first reported examples of nonribosomal peptides containing this residue. The ldlld chiral sequence found for the three compounds was in agreement with that reported for previously isolated pentaminomycins and consistent with the epimerization domains present in the putative nonribosomal peptide synthetase (NRPS) biosynthetic gene cluster.

Neighbourhood walkability and physical activity: moderating role of a physical activity intervention in overweight and obese older adults with metabolic syndrome.

BACKGROUND: While urban built environments might promote active ageing, an infrequently studied question is how the neighbourhood walkability modulates physical activity changes during a physical activity intervention programme in older adults. We assessed the influence of objectively assessed neighbourhood walkability on the change in physical activity during the intervention programme used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial. METHOD: The present study involved 228 PREDIMED-Plus senior participants aged between 55 and 75, recruited in Palma de Mallorca (Spain). Overweight/obese older adults with metabolic syndrome were randomised to an intensive weight-loss lifestyle intervention or a control group. A walkability index (residential density, land use mix, intersections density) was calculated using geographic information systems (1 km sausage-network buffer). Physical activity was assessed using accelerometer and a validated questionnaire, at baseline and two follow-up visits (6-months and 1-year later). Generalised additive mixed models were fitted to estimate the association between the neighbourhood walkability index and changes in physical activity during follow-up. RESULTS: Higher neighbourhood walkability (1 z-score increment) was associated with moderate-to-vigorous accelerometer assessed physical activity duration, (ß = 3.44; 95% CI = 0.52; 6.36 min/day). When analyses were stratified by intervention arm, the association was only observed in the intervention group (ß = 6.357; 95% CI = 2.07;10.64 min/day) (P for interaction = 0.055). CONCLUSIONS: The results indicate that the walkability of the neighbourhood could support a physical activity intervention, helping to maintain or increase older adults' physical activity.

Activation and Identification of a Griseusin Cluster in Streptomyces sp. CA-256286 by Employing Transcriptional Regulators and Multi-Omics Methods.

Streptomyces are well-known producers of a range of different secondary metabolites, including antibiotics and other bioactive compounds. Recently, it has been demonstrated that "silent" biosynthetic gene clusters (BGCs) can be activated by heterologously expressing transcriptional regulators from other BGCs. Here, we have activated a silent BGC in Streptomyces sp. CA-256286 by overexpression of a set of SARP family transcriptional regulators. The structure of the produced compound was elucidated by NMR and found to be an N-acetyl cysteine adduct of the pyranonaphtoquinone polyketide 3'-O-α-d-forosaminyl-(+)-griseusin A. Employing a combination of multi-omics and metabolic engineering techniques, we identified the responsible BGC. These methods include genome mining, proteomics and transcriptomics analyses, in combination with CRISPR induced gene inactivations and expression of the BGC in a heterologous host strain. This work demonstrates an easy-to-implement workflow of how silent BGCs can be activated, followed by the identification and characterization of the produced compound, the responsible BGC, and hints of its biosynthetic pathway.

Complementary music therapy for cancer patients in at-home palliative care and their caregivers: protocol for a multicentre randomised controlled trial.

BACKGROUND: Patients with advanced cancer, receiving at-home palliative care, are subject to numerous symptoms that are changeable and often require attention, a stressful situation that also impacts on the family caregiver. It has been suggested that music therapy may benefit both the patient and the caregiver. We propose a study to analyse the efficacy and cost utility of a music intervention programme, applied as complementary therapy, for cancer patients in palliative care and for their at-home caregivers, compared to usual treatment. METHOD: A randomised, double-blind, multicentre clinical trial will be performed in cancer patients in at-home palliative care and their family caregivers. The study population will include two samples of 40 patients and two samples of 41 caregivers. Participants will be randomly assigned either to the intervention group or to the control group. The intervention group will receive a seven-day programme including music sessions, while the control group will receive seven sessions of (spoken word) therapeutic education. In this study, the primary outcome measure is the assessment of patients' symptoms, according to the Edmonton Symptom Assessment System, and of the overload experienced by family caregivers, measured by the Caregiver Strain Index. The secondary outcomes considered will be the participants' health-related quality of life, their satisfaction with the intervention, and an economic valuation. DISCUSSION: This study is expected to enhance our understanding of the efficacy and cost-utility of music therapy for cancer patients in palliative care and for their family caregivers. The results of this project are expected to be applicable and transferrable to usual clinical practice for patients in home palliative care and for their caregivers. The approach described can be incorporated as an additional therapeutic resource within comprehensive palliative care. To our knowledge, no previous high quality studies, based on a double-blind clinical trial, have been undertaken to evaluate the cost-effectiveness of music therapy. The cost-effectiveness of the project will provide information to support decision making, thereby improving the management of health resources and their use within the health system. TRIAL REGISTRATION: The COMTHECARE study is registered at Clinical Trials.gov, NCT04052074. Registered 9 August, 2019.

Intervention to improve quality of sleep of palliative patient carers in the community: protocol for a multicentre randomised controlled trial.

BACKGROUND: Sleep disorders are commonly experienced by community caregivers for persons with cancer, with at least 72% reporting moderate to severe disorders. A consequence of this condition, which is associated with the presence of overload in the caregiver, is the increased risk of clinical depression. The aim of this study is to evaluate the effects of music on the sleep quality achieved by informal caregivers for cancer patients receiving home palliative care. In addition, we will assess the influence of specific variables that could modify these effects, analyse the correlates related to nocturnal wakefulness and consider the diurnal consequences according to the sleep characteristics identified. METHODS: This single-blind, multicentre, randomised clinical trial will focus on informal providers of care for cancer patients. Two samples of 40 caregivers will be recruited. The first, intervention, group will receive seven music-based sessions. The control group will be masked with seven sessions of therapeutic education (reinforcing previous sessions). Outcomes will be evaluated using the Pittsburgh Sleep Quality Index, a triaxial accelerometer, EuroQol-5D-5L, the Caregiver Strain Index, the Epworth Sleepiness Scale and the Client Satisfaction Questionnaire. The caregivers' satisfaction with the intervention performed will also be examined. DISCUSSION: This study is expected to extend our understanding of the efficacy of music therapy in enhancing the sleep quality of caregivers for patients receiving home palliative care. To our knowledge, no reliable scientific investigations of this subject have previously been undertaken. Music is believed to benefit certain aspects of sleep, but this has yet to be proven and, according to a Cochrane review, high-quality research in this field is necessary. One of the main strengths of our study, which heightens the quality of the randomised clinical trial design, is the objective assessment of physical activity by accelerometry and the use of both objective and subjective measures of sleep in caregivers. Music therapy for the caregivers addressed in this study is complementary, readily applicable, provokes no harmful side effects and may produce significant benefits. TRIAL REGISTRATION: The IMECA study is registered at Clinical Trials.gov, ClinicalTrials.gov Identifier: NCT04491110 . Registered 29 July, 2020.

Validation of a modified version of the Spanish Geriatric Oral Health Assessment Index (GOHAI-SP) for adults and elder people.

BACKGROUND: The Geriatric Oral Health Assessment Index (GOHAI) was developed and validated in 1990 and translated into Spanish in 1999. Since then, the original version has been used in numerous studies, but it has not been re-evaluated in terms of language in the new generations of older adults. The purpose of this study is to confirm the validity of the Spanish version of the Geriatric Oral Health Assessment Index (GOHAI-SP) after three decades to be used as part of an ongoing field trial. METHODS: The GOHAI-SP was pilot tested in a focus group to confirm linguistic comprehension. A version with minor language changes was administered to individuals with metabolic syndrome aged 55-75 years from one health care district in southern Spain as part of an ongoing field trial (PREDIMED-Plus). Clinical evaluation included assessment of dental and periodontal status. The psychometric properties of the GOHAI-SP were evaluated through stability and internal consistency measures, and concurrent and discriminant validity were assessed. RESULTS: The new version of the GOHAI-SP was administered to 100 individuals. The application time was reduced by 7 min. The alpha value for reliability was 0.87. The item-scale correlation coefficients ranged from 0.54 to 0.75, and the test-re-test correlation for the total score was 0.75. There were inverse correlations between GOHAI-SP scores and the number of lost teeth and the decayed-missing-filled teeth index (p < 0.001). CONCLUSIONS: The GOHAI-SP questionnaire remains a valid and useful tool to assess oral health-related quality of life in primary health care settings. A linguistic update of the questionnaire brought improvements to the instrument application. TRIAL REGISTRATION: The PREDIMED-Plus trial is registered in the ISRCTN registry with reference number ISRCTN89898870. Registration date: 4th July 2014.

Perception, knowledge, and attitudes towards molar incisor hypomineralization among Spanish dentists: a cross-sectional study.

BACKGROUND: Molar incisor hypomineralization (MIH) is a growing health problem, and its treatment is a challenge. The purpose of the present study was to evaluate and compare the perceptions, knowledge, and clinical experiences of MIH in general dental practitioners (GDPs) and paediatric dentists (PDs) in Spain. METHODS: All dentists belonging to the College of Dentists of the Region of Murcia, in the South-East of Spain, were invited to participate in a cross-sectional survey. They were asked to complete a two-part questionnaire including sociodemographic profiles and knowledge, experience, and perceptions of MIH. Data were analysed using Pearson's chi-square test, Fisher's exact test and Cramer's V test. RESULTS: The overall response rate was 18.6% (214/1147). Most respondents were aged 31-40 years (44.86%), with more than 15 years of professional experience (39.72%). They worked mainly in the private sector (84.58%) and were licensed in dentistry (74.30%): 95.45% of PDs had detected an increase in the incidence of MIH in recent years (p <  0.001). Only 23.80% of GDPs claimed to have made a training course on MIH. With respect to the aetiology, chronic medical conditions (p = 0.029) and environmental pollutants (p = 0.008) were the only factors that showed significant between-group differences. Durability (p = 0.009) and remineralization potential (p = 0.018) were the factors where there was a between-group difference in the choice of the restoration material. In the case of post-eruptive fractures and opacities, the preferred material for both groups was resin-modified glass ionomer (RMGIC). However, in incisor lesions, composite was the material of choice for both groups, with significant differences (p = 0.032) in the use of glass ionomer. Most respondents expressed a need for continuing education on MIH. CONCLUSION: Spanish dentists perceived an increase in the incidence of MIH. The material of choice was RMGIC for non-aesthetic sectors and composite for incisors. Dentists believe it is difficult or very difficult to manage MIH, since the long-term success of restorations of MIH lesions is compromised because resin adhesion is not good. Both GDPs and PDs believe they need more training on the aetiology, diagnosis, and treatment of MIH.

Cacaoidin, First Member of the New Lanthidin RiPP Family.

Lantibiotics are ribosomally synthesized and post-translationally modified peptides (RiPPs) characterized by the presence of lanthionine or methyllanthionine rings and their antimicrobial activity. Cacaoidin, a novel glycosylated lantibiotic, was isolated from a Streptomyces cacaoi strain and fully characterized by NMR, mass spectrometry, chemical derivatization approaches and genome analysis. The new molecule combines outstanding structural features, such as a high number of d-amino acids, an uncommon glycosylated tyrosine residue and an unprecedented N,N-dimethyl lanthionine. This latter feature places cacaoidin within a new RiPP family located between lanthipeptides and linaridins, here termed lanthidins. Cacaoidin displayed potent antibacterial activity against Gram-positive pathogens including Clostridium difficile. The biosynthetic gene cluster showed low homology with those of other known lanthipeptides or linaridins, suggesting a new RiPP biosynthetic pathway.

Open Targets: a platform for therapeutic target identification and validation.

We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org.

New Napyradiomycin Analogues from Streptomyces sp. Strain CA-271078.

As part of our continuing efforts to discover new bioactive compounds from microbial sources, a reinvestigation of extracts of scaled-up cultures of the marine-derived Streptomyces sp. strain CA-271078 resulted in the isolation and structural elucidation of four new napyradiomycins (1-3, 5). The known napyradiomycin SC (4), whose structural details had not been previously described in detail, and another ten related known compounds (6-15). The structures of the new napyradiomycins were characterized by HRMS and 1D- and 2D-NMR spectroscopies and their relative configurations were established through a combination of molecular modelling with nOe and coupling constants NMR analysis. The absolute configuration of each compound is also proposed based on biosynthetic arguments and the comparison of specific rotation data with those of related compounds. Among the new compounds, 1 was determined to be the first non-halogenated member of napyradiomycin A series containing a functionalized prenyl side chain, while 2-4 harbor in their structures the characteristic chloro-cyclohexane ring of the napyradiomycin B series. Remarkably, compound 5 displays an unprecedented 14-membered cyclic ether ring between the prenyl side chain and the chromophore, thus representing the first member of a new class of napyradiomycins that we have designated as napyradiomycin D1. Anti-infective and cytotoxic properties for all isolated compounds were evaluated against a set of pathogenic microorganisms and the HepG2 cell line, respectively. Among the new compounds, napyradiomycin D1 exhibited significant growth-inhibitory activity against methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, and HepG2.

New 3-Hydroxyquinaldic Acid Derivatives from Cultures of the Marine Derived Actinomycete Streptomyces cyaneofuscatus M-157.

Fractionation of the bioactive extract of a culture of the marine derived actinomycete Streptomyces cyaneofuscatus M-157 led to the isolation of the known 3-hydroxyquinaldic acid (4), its amide (5) and three new derivatives (1⁻3) containing different amino acid residues. The structures of the new molecules (1⁻3), including their absolute configuration, were determined by the analysis of their ESI-TOF MS and one-dimensional (1D) and two-dimensional (2D) NMR spectra and advanced Marfey's analysis of their hydrolyzation products. Compound 3 spontaneously dimerized in solution to give the disulfide derivative 6. Unfortunately, none of the new compounds isolated confirmed the antimicrobial activity found in the bacterial extract, perhaps indicating that such antibacterial activity might be due to presence in the extract at the trace level of larger bioactive 3-hydroxyquinaldic acid derivatives from which compounds 1⁻3 are biosynthetic precursors. Cytotoxicity tests confirmed the moderate and weak IC50 values of 15.6 and 51.5 µM for compounds 5 and 1, respectively.

Evidence of Benefit of Telerehabitation After Orthopedic Surgery: A Systematic Review.

BACKGROUND: In addition to traditional physiotherapy, studies based on telerehabilitation programs have published the results of effectiveness, validity, noninferiority, and important advantages in some neurological, cognitive, and musculoskeletal disorders, providing an opportunity to define new social policies and interventions. OBJECTIVES: The aim of this systematic review is to investigate the effects of telerehabilitation after surgical procedures on orthopedic conditions as well as to describe how interventions are designed and to determine whether telerehabilitation is comparable with conventional methods of delivery. This systematic review summarizes the levels of evidence and grades of recommendation regarding telerehabilitation intervention (synchronous or asynchronous provided via the telerehabilitation medium, either in conjunction with, or in isolation of, other treatment interventions) after surgical procedures on orthopedic conditions. METHODS: Study quality was assessed using the Physiotherapy Evidence Database (PEDro) scores and grade of recommendation following the recommendation of the Oxford Centre for Evidence-Based Medicine. RESULTS: We found 3 studies with PEDro scores between 6 and 8, which is considered as level 1 evidence (good; 20% [3/15]), 4 studies with a score of 5, which is considered as level 2 evidence (acceptable; 27% [4/15]), and the remaining 8 studies had scores of 4 or less, which is considered (poor; 53% [8/15]). A total of 1316 participants received telerehabilitation intervention in the selected studies, where knee and hip replacement were 75% of all the studies. Strong and moderate grades of evidence (grade of recommendation A-B) were found in knee and hip replacement interventions. Studies on the upper limb were 25% of the studies, but only 1 study presented a moderate grade of evidence (grade of recommendation B) and the rest were of poor methodological quality with weak evidence (grade of recommendation C). CONCLUSIONS: Conclusive evidence on the efficacy of telerehabilitation for treatment after an orthopedic surgery, regardless of pathology, was not obtained. We found strong evidence in favor of telerehabilitation in patients following total knee and hip arthroplasty and limited evidence in the upper limb interventions (moderate and weak evidence). Future research needs to be more extensive and conclusive. To the best of the authors' knowledge, this is the first attempt at evaluating the quality of telerehabilitation intervention research after surgical procedures on orthopedic conditions in a systematic review. Clinical messages and future research recommendations are included in the review.

[Validation of the knowledge and attitudes of health professionals in the Living Will Declaration process]. / Validación del cuestionario de conocimientos y actitudes de los profesionales sanitarios en el proceso de declaración de voluntades vitales anticipadas.

OBJECTIVE: Evaluate the validity and reliability of the knowledge and attitudes of health professionals questionnaire on the Living Will Declaration (LWD) process. DESIGN: Cross-sectional study structured into 3 phases: (i)pilot questionnaire administered with paper to assess losses and adjustment problems; (ii)assessment of the validity and internal reliability, and (iii)assessment of the pre-filtering questionnaire stability (test-retest). LOCATION: Costa del Sol (Malaga) Health Area. January 2014 to April 2015. PARTICIPANTS: Healthcare professionals of the Costa del Sol Primary Care District and the Costa del Sol Health Agency. There were 391 (23.6%) responses, and 100 participated in the stability assessment (83 responses). MAIN MEASUREMENTS: The questionnaire consisted of 2 parts: (i)Knowledge (5 dimensions and 41 items), and (ii)Attitudes (2 dimensions and 17 items). RESULTS: In the pilot study, none of the items lost over 10%. In the evaluation phase of validity and reliability, the questionnaire was reduced to 41 items (29 of knowledge, and 12 of attitudes). In the stability evaluation phase, all items evaluated met the requirement of a kappa higher than 0.2, or had a percentage of absolute agreement exceeding 75%. CONCLUSIONS: The questionnaire will identify the status and areas for improvement in the health care setting, and then will allow an improved culture of LWD process in general population.

Phase II trial of ofatumumab plus ESHAP (O-ESHAP) as salvage treatment for patients with relapsed or refractory classical Hodgkin lymphoma after first-line chemotherapy.

The management of recurrent/refractory (R/R) Hodgkin lymphoma (HL) remains challenging. Previously published data have shown some efficacy of rituximab in this setting. The purpose of this phase II trial was to investigate the activity of ofatumumab in combination with etoposide, steroids, cytarabine and cisplatin (O-ESHAP) in 62 patients with R/R classical HL. Treatment consisted of ESHAP plus ofatumumab 1000 mg on days 1 and 8 of the first cycle and day 1 of the second and third cycles. O-ESHAP was well tolerated with only 3% of patients requiring treatment discontinuation because of adverse events. Overall response rate was 73% (44% complete metabolic response). In multivariate analysis, early relapse (P < 0·001), bulky disease (P < 0·001) and B symptoms (P < 0·001) were the most important prognostic factors for response. No failures of stem cell mobilization were observed. The high response rate, particularly the complete metabolic response rate, the low toxicity profile, and the high mobilizing potential of the O-ESHAP regimen suggest that patients with R/R HL may benefit from this salvage regimen. However, with the encouraging results observed with other new therapeutic agents in HL, the O-ESHAP regimen could be restricted to patients failing these agents or to those with R/R nodular lymphocyte-predominant HL.