Efficacy and efficiency of a new therapeutic approach based on activityoriented proprioceptive antiedema therapy (TAPA) for edema reduction and improved occupational performance in the rehabilitation of breast cancer-related arm lymphedema in women: a controlled, randomized clinical trial

Antecedentes: La Sociedad Internacional de Linfología (ISL) define el linfedema como una manifestación externa (y/o interna) de la insuficiencia del sistema y transporte linfático disminuido, que suele seguir un curso crónico y progresivo y que requiere de una atención biopsicosocial de por vida. El linfedema es una de las complicaciones más importantes y frecuentes del cáncer de mama (CM) – actualmente el tumor más diagnosticado en el mundo- y de sus tratamientos. La causa de linfedema secundario más habitual en países desarrollados es el secundario a neoplasias, siendo el más frecuente el linfedema secundario a CM en miembro superior (LSCMS). Clínicamente se manifiesta como tumefacción y puede provocar cambios irreversibles en los tejidos con alto riesgo de infección. Produce cambios en funciones y estructuras corporales, como la forma del brazo, fatiga, angustia, cambios en la imagen corporal, sensación de pesadez, tirantez, entumecimiento, limitación del rango articular, alteraciones de la piel, etc., dificultando la realización, restringiendo la participación en actividades de cuidado personal, productivas, de ocio y participación social e impactando negativamente por tanto en la calidad de vida relacionada con la salud (CVRS). La Terapia Ocupacional (TO) aporta un enfoque beneficioso único en la rehabilitación de la participación en las áreas fundamentales de la vida. No existe un tratamiento definitivo para el linfedema, siendo considerada, con una moderada evidencia, la terapia descongestiva compleja (TDC) como el estándar en el tratamiento conservador inicial del LSCMS. Objetivo: El objetivo de esta investigación fue verificar la eficacia y la eficiencia de un tratamiento experimental, la terapia antiedema propioceptiva orientada a la actividad (TAPA) en la rehabilitación del LSCMS en mujeres en estadío I y II, según clasificación de la ISL, comparándola con el tratamiento estándar, TDC. Metodología: Ensayo clínico controlado, multicéntrico, aleatorizado por estratificación en dos gradientes, con dos brazos paralelos, longitudinal y simple ciego. La población de estudio estuvo conformada por mujeres intervenidas de CM, diagnosticadas de LSCMS, en estadío I y II, derivadas a diferentes instituciones sanitarias de Córdoba y Aragón. Se evaluaron variables sociodemográficas y clínicas, CVRS, sensaciones percibidas de dolor, tirantez y pesadez y funcionalidad del miembro superior en el desempeño ocupacional antes, inmediatamente después, al mes y a los tres meses de la intervención. Se realizó un análisis estadístico con intención de tratar, un análisis bivariado, comprobando que las variables cuantitativas siguieron una distribución normal. Se calcularon los diferenciales para variables continuas, que se sometieron posteriormente a un análisis de covarianza. Resultados: Participaron en el estudio 51 mujeres, de las que 25 recibieron TDC y 26, TAPA. La edad media de las participantes fue de 59,24 años (DE ± 9,55), y la mayoría de las mujeres se encontraban en activo (n = 26; 51%) o jubiladas (n = 19; 37%). El Índice de masa corporal medio fue de 28.17 (DE ±4,82) y la media de número de ganglios extirpados fue de 13.1 (DE ±8,47). Sólo dos participantes (4%) se sometieron a cirugía conservadora y las 49 restantes (96%), a mastectomía. La mayoría de las participantes no tuvieron complicaciones tras la intervención quirúrgica (n=43; 84%). El nivel de estado de salud autopercibido tuvo una correlación positiva con la sensación de dolor (p=0,048) y con la funcionalidad de miembros superiores en el desempeño ocupacional (p=0,004) y ésta con la dimensión social de la CVRVS (p=0,037). El análisis de covarianza (ANCOVA) mostró que la dimensión social de CVRS (p=0,039) y el balance articular de rotación externa de hombro (p=0,045) mejoró más en el grupo que recibió la intervención experimental, TAPA. Ambos grupos de intervención mejoraron de manera muy significativa la reducción del volumen de la extremidad afecta (p<0,001), las dimensiones física (p<0,001) y psicológica (p=0,002) de CVRS y el balance articular de flexión de hombro (p=0,013), aunque no hubo diferencias significativas entre grupos. Conclusiones: TAPA podría ser una alternativa eficaz a la TDC en la rehabilitación del LSCMS en estadío I y II en mujeres, apta para personas que no desean utilizar terapias compresivas, también para quienes no las toleran y para quienes las tienen contraindicadas; facilita la toma de decisiones terapéuticas, estableciendo dosis exactas de tratamiento para ambos estadíos; es aplicable en los niveles fundamentales de atención sanitaria, primaria y especializada, con un enfoque multidisciplinar y favorece una gestión eficiente de los recursos sanitarios, al requerir de una menor inversión de material y de tiempo empleado que la TDC.Background: The International Society of Lymphology (ISL) defines lymphedema as an external (and/or internal) manifestation of system failure and diminished lymphatic transport, which usually follows a chronic and progressive course and requires lifelong biopsychosocial care. Lymphedema is one of the most important and frequent complications of breast cancer (BC) - currently the most diagnosed tumor in the world - and its treatments. The most common cause of secondary lymphedema in developed countries is secondary to neoplasms, the most common being lymphedema secondary to BC in the upper limb (BCRAL). Clinically it manifests as swelling and can cause irreversible changes in tissues with a high risk of infection. Produces changes in body functions and structures, such as the shape of the arm, fatigue, anguish, changes in body image, a feeling of heaviness, tightness, pain, limitation of joint range, skin changes, etc., making it difficult to perform, restricting participation in personal care, productive, leisure and social participation activities and negatively impacting therefore on the quality of life related to health (HRQoL). Occupational Therapy (OT) brings a unique beneficial approach to the rehabilitation of participation in the fundamental areas of life. There is no definitive treatment for lymphedema, the complex decongestive therapy (CDT), with moderate evidence, is considered as the standard in the initial conservative treatment of BCRAL. Aim: The aim of this research was to verify the efficacy and efficiency of an experimental treatment, activity-oriented proprioceptive anti-edema therapy (TAPA) in the rehabilitation of BCRAL in women in stage I and II, according to the ISL classification, comparing it with the standard treatment, CDT. Methods: Controlled, multicenter clinical trial, randomized by stratification in two gradients, with two parallel arms, longitudinal and single blind. The study population consisted in women operated on for BC, diagnosed with BCRAL, in stage I and II, referred to different health institutions of Córdoba and Aragón. Sociodemographic and clinical variables, HRQoL, perceived sensations of pain, tightness and heaviness, and functionality of the upper limb in occupational performance were evaluated before, immediately after, one month and three months after the intervention. A statistical analysis was performed with intention to treat, a bivariate analysis, verifying that the quantitative variables followed a normal distribution. Differentials were calculated for continuous variables, which were subsequently subjected to an analysis of covariance. Results: 51 women participated in the study, of whom 25 received CDT and 26 TAPA. The mean age of the participants was 59.24 years (SD ± 9.55), and most of the women were active (n = 26; 51%) or retired (n = 19; 37%). The mean body mass index was 28.17 (SD±4.82) and the mean number of lymph nodes removed was 13.1 (SD±8.47). Only two participants (4%) underwent breast conservative surgery, while the rest 49 (96%) underwent a mastectomy. Most of the participants had no complications after surgery (n = 43; 84%). The social dimension of HRQOL had a positive correlation with the functionality of the upper extremities (p=0.037). The level of self-perceived health status was also significantly correlated with the sensation of pain (p=0.048) and with the functionality of the upper limbs in occupational performance (p=0.004). The analysis of covariance (ANCOVA) showed that the social dimension of HRQoL (p=0,039) and shoulder external rotation joint balance (p=0.045) improved more in the group that received the experimental intervention, TAPA. Both intervention groups improved very significantly the volume reduction of the affected upper limb (p<0,001), the physical (p<0,001) and psychological (p=0.002) dimensions of HRQoL and the joint balance of shoulder flexion, although there were no significant differences between groups. Both the material and the time spent by the therapist were less with the experimental treatment. Conclusions: TAPA could be an effective alternative to CDT in the rehabilitation of stage I and II LSCMS in women, suitable for people who do not want to use compression therapies, also for those who do not tolerate them and for those who have them contraindicated; facilitates therapeutic decision-making, establishing exact doses of treatment for both stages. TAPA is applicable at the fundamental levels of health care, primary and specialized, with a multidisciplinary approach and favors efficient management of health resources, as it requires less investment of material and time than CDT

A usability study in patients with stroke using MERLIN, a robotic system based on serious games for upper limb rehabilitation in the home setting

Neuroscience and neurotechnology are transforming stroke rehabilitation. Robotic devices, in addition to telerehabilitation, are increasingly being used to train the upper limbs after stroke, and their use at home allows us to extend institutional rehabilitation by increasing and prolonging therapy. The aim of this study is to assess the usability of the MERLIN robotic system based on serious games for upper limb rehabilitation in people with stroke in the home environment.This research is part of a MERLIN project, which has received funding from EIT Health (Grant no. 20649). EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union which receives support from the European Union’s Horizon 2020 Research and innovation programme

Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) for Shoulder Mobility Improvement in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Multicenter Controlled Clinical Trial

Lymphedema, secondary to breast cancer (BCRL), is the abnormal accumulation of protein-rich fluid in the interstitium caused by a malfunction of the lymphatic system. It causes swelling, deficiencies in upper limb functions and structures, sensory pain and emotional alterations, which have a chronic course and affect the upper limb’s functionality. This study aims to verify the efficacy and efficiency in the upper limb´s functionality of a protocolized experimental approach based on occupational therapy, TAPA (activity-oriented proprioceptive antiedema therapy), in the rehabilitation of BCRL in stages I and II, comparing it with the conservative treatment considered as the standard, complex decongestive therapy (CDT), through a multicenter randomized clinical trial.The study has been financed in the call for competitive competition of research and innovation projects in the field of Primary Care, Regional Hospitals and High Resolution Hospital Centers of the Public Health System of Andalusia for the year 2021, of the Andalusian Public Foundation Progress and Health, according to the definitive list of funded projects, published on 23 December 2021, with EXP. No.: AP-0160-2021-C2-F2, also in the call for “Grants for research projects in Occupational Therapy. Call 2020”, granted by the Professional Association of Occupational Therapists of Extremadura (COPTOEX), Spain and, in 2020, received an economic contribution from the Research Group in Primary Health Care of Aragon (GAIAP-B21-17R group)

Impact of Activity-Oriented Propioceptive Antiedema Therapy on the Health-Related Quality of Life of Women with Upper-Limb Lymphedema Secondary to Breast Cancer—A Randomized Clinical Trial

Alterations derived from lymphedema in the upper-limb secondary to breast cancer-related lymphedema (BCRL) decrease the health-related quality of life (HRQoL), but there is limited evidence of the impact of the different interventions on it. The aim of this research was to compare the effect of conventional treatment with another treatment based on Activity-Oriented Antiedema Proprioceptive Therapy (TAPA) on HRQoL in women diagnosed with BCRL.This research was funded by the Call for research and innovation projects in the field of primary care, regional hospitals and high-resolution hospital centres of the Public Health System of Andalusia in 2021 by the Progreso y Salud Foundation, of the Ministry of Health and Families of the Junta de Andalucía, with EXP. No.: AP-0160-2021-C2-F2. He has also been awarded a scholarship by the Professional Association of Occupational Therapists of Extremadura (COPTOEX) (Spain) call 2020 and awarded a financial contribution from the Research Group in Primary Health Care of Aragon (GAIAP-B21-17R group), recognized and financed by the Government of Aragón (Spain) and by Feder Funds “Another way of making Europe”

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

The evolution of the ventilatory ratio is a prognostic factor in mechanically ventilated COVID-19 ARDS patients

Background: Mortality due to COVID-19 is high, especially in patients requiring mechanical ventilation. The purpose of the study is to investigate associations between mortality and variables measured during the first three days of mechanical ventilation in patients with COVID-19 intubated at ICU admission. Methods: Multicenter, observational, cohort study includes consecutive patients with COVID-19 admitted to 44 Spanish ICUs between February 25 and July 31, 2020, who required intubation at ICU admission and mechanical ventilation for more than three days. We collected demographic and clinical data prior to admission; information about clinical evolution at days 1 and 3 of mechanical ventilation; and outcomes. Results: Of the 2,095 patients with COVID-19 admitted to the ICU, 1,118 (53.3%) were intubated at day 1 and remained under mechanical ventilation at day three. From days 1 to 3, PaO2/FiO2 increased from 115.6 [80.0-171.2] to 180.0 [135.4-227.9] mmHg and the ventilatory ratio from 1.73 [1.33-2.25] to 1.96 [1.61-2.40]. In-hospital mortality was 38.7%. A higher increase between ICU admission and day 3 in the ventilatory ratio (OR 1.04 [CI 1.01-1.07], p = 0.030) and creatinine levels (OR 1.05 [CI 1.01-1.09], p = 0.005) and a lower increase in platelet counts (OR 0.96 [CI 0.93-1.00], p = 0.037) were independently associated with a higher risk of death. No association between mortality and the PaO2/FiO2 variation was observed (OR 0.99 [CI 0.95 to 1.02], p = 0.47). Conclusions: Higher ventilatory ratio and its increase at day 3 is associated with mortality in patients with COVID-19 receiving mechanical ventilation at ICU admission. No association was found in the PaO2/FiO2 variation

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

A usability study in patients with stroke using MERLIN, a robotic system based on serious games for upper limb rehabilitation in the home setting

Background: Neuroscience and neurotechnology are transforming stroke rehabilitation. Robotic devices, in addition to telerehabilitation, are increasingly being used to train the upper limbs after stroke, and their use at home allows us to extend institutional rehabilitation by increasing and prolonging therapy. The aim of this study is to assess the usability of the MERLIN robotic system based on serious games for upper limb rehabilitation in people with stroke in the home environment. Methods: 9 participants with a stroke in three diferent stages of recovery (subacute, short-term chronic and long term chronic) with impaired arm/hand function, were recruited to use the MERLIN system for 3 weeks: 1 week training at the Maimonides Biomedical Research Institute of Cordoba (IMIBIC), and 2 weeks at the patients’ homes. To evaluate usability, the System Usability Scale (SUS), Adapted Intrinsic Motivation Inventory (IMI), Quebec User Evaluation of Satisfaction with assistive Technology (QUEST), and the ArmAssist Usability Assessment Questionnaire were used in the post-intervention. Clinical outcomes for upper limb motor function were assessed pre- and post-intervention. Results: 9 patients participated in and completed the study. The usability assessment reported a high level of satisfaction: mean SUS score 71.94% (SD=16.38), mean QUEST scale 3.81 (SD=0.38), and mean Adapted IMI score 6.12 (SD=1.36). The results of the ArmAssist Questionnaire showed an average of 6 out of 7, which indicates that MERLIN is extremely intuitive, easy to learn and easy to use. Regarding clinical assessment, the Fugl-Meyer scores showed moderate improvements from pre- to post-intervention in the total score of motor function (p=0.002). There were no signifcant changes in the Modifed Ashworth scale outcomes (p=0.169). Conclusions: This usability study indicates that home-based rehabilitation for upper limbs with the MERLIN system is safe, useful, feasible and motivating. Telerehabilitation constitutes a major step forward in the use of intensive rehabilitation at home.This research is part of a MERLIN project, which has received funding from EIT Health (Grant no. 20649). EIT Health is supported by the European Institute of Innovation and Technology (EIT), a body of the European Union which receives support from the European Union’s Horizon 2020 Research and innovation programme.Ye

Effect of Conservative Rehabilitation Interventions on Health-Related Quality of Life in Women with Upper Limb Lymphedema Secondary to Breast Cancer: A Systematic Review

Breast cancer-related lymphedema (BCRL) of the upper limb is a very common condition in women undergoing breast cancer treatment; it can cause considerable alterations in the daily life of patients and a decrease in their health-related quality of life (HRQoL). Currently, there are many conservative therapies that try to palliate the symptoms, but the results are still controversial and there are still no globally accepted treatments. The purpose of this article is to determine the effect, according to the current available evidence, on HRQoL of different conservative interventions in the rehabilitation of BCRL in the upper limb in women. Eighteen articles that compared the effects of standard treatments, such as manual lymphatic drainage-based decongestive therapy or compression measures, and other newer treatments, including new technologies and other types of treatment programs, were reviewed. According to the results of this review, the most recommended modality for the improvement of HRQoL would be a complex decongestive technique without manual lymphatic drainage. Although there are clinical trials that have demonstrated the effectiveness of various treatments, the results of the positive effects on HRQoL remain highly controversial. There is a need to continue to develop studies to help guide therapeutic decisions that can promote HRQoL in women affected by upper limb BCRL