Resilience in care organisations: challenges in maintaining support for vulnerable people in Europe during the Covid-19 pandemic.

The Covid-19 pandemic has challenged the resilience of care organisations (and those dependent on them), especially when services are stopped or restricted. This study focuses on the experiences of care organisations that offer services to individuals in highly precarious situations in 10 European countries. It is based on 32 qualitative interviews and three workshops with managers and staff. The four key types of organisations reviewed largely had the same adaptation patterns in all countries. The most drastic changes were experienced by day centres, which had to suspend or digitise services, whereas night shelters and soup kitchens had to reorganise broadly their work; residential facilities were minimally affected. Given the drastic surge in demand for services, reliance on an overburdened (volunteer) workforce, and a lack of crisis plans, the care organisations with long-term trust networks with clients and intra-organisational cooperation adapted easier. The outcomes were worse for new clients, migrants, psychologically vulnerable people, and those with limited communicative abilities.

Efectos del entrenamiento con restricción del flujo sanguíneo sobre el tejido muscular y óseo: un estudio piloto / Effects of blood flow restriction training on bone and muscle tissue: a pilot study

Los estudios completados hasta el momento respaldan la hipótesis de que el entrenamiento de baja intensidad (EBI) asociado con restricción del flujo sanguíneo (RFS) aumenta la hipertrofia muscular (HM) y fuerza dinámica máxima (FDM). Sin embargo, se carece de evidencias firmes que relacionen esta metodología con adaptaciones en el hueso. El objetivo de este estudio fue establecer el efecto de cuatro protocolos de EBI asociados a RFS, en la HM, FDM, masa ósea (MO), densidad mineral ósea (DMO) y concentración mineral ósea (CMO) del miembro inferior en un periodo de 11 semanas de entrenamiento. Dieciséis individuos medianamente entrenados fueron reclutados. Se realizó una distribución aleatoria de los participantes quedando distribuidos. G1: Electro Estimulación Neuromuscular (EENM) + RFS; G2: Caminata en treadmill + RFS; G3: Sentadilla 90º + RFS; G4: Solo RFS. Se utilizó medición directa de la FDM, Antropometría y Densitometría Radiológica Dual para medir las variables. Las mediciones fueron realizadas al inicio y al final de las 11 semanas. En la variable HM los tratamientos de caminata + RFS y EENM + RFS registraron las principales mejoras frente al resto de las intervenciones. La FDM se ve afectada y mejorada por la EENM, la caminata y las sentadillas asociados a RFS, de similar manera a solo la aplicación de RFS. Se observaron modificaciones en la MO, DMO y CMO. La EENM + RFS lidero los resultados, mejorando la DMO y CMO. La caminata + RFS mostro mejorar la MO y la DMO al mismo tiempo. La RFS sumado a los estímulos, EENM, caminata y sentadilla genera efectos positivos sobre la HM, la FDM y tejido óseo del miembro inferior. La RFS también genera cambios sin la asociación a otro estimulo, pero en menor medida. No se logró establecer una diferencia estadísticamente significativa (p > 0,05) entre los grupos

The studies completed so far support the hypothesis that low intensity training (LIT ) associated with blood flow restriction (BFR) increases muscle hypertrophy (MH) and maximum dynamic force (MDF). However, there is a lack of firm evidence linking this methodology with adaptations in the bone. The objective of this study was to establish the effect of four LIT protocols associated with BFR, in the MH, MDF, bone mass (BM), bone mineral density (BMD) and bone mineral concentration (BMC) of the lower limb over a period of 11 weeks of training. Sixteen moderately trained individuals were recruited. A random distribution of the participants was carried out, being distributed. G1: Electro-Neuromuscular Stimulation (ENMS) + BFR; G2: Treadmill walk + BFR; G3: Squat 90º + BFR; G4: Only BFR. Direct measurement of the MDF, Anthropometry and Dual Radiological Densitometry was used to measure the variables. The measurements were made at the beginning and the end of the 11 weeks. In the MH variable, the walking treatments + BFR and ENMS + BFR registered main improvements compared to the rest of the interventions. The MDF is affected and improved by the ENMS, walking and squats are associated with BFR, in a similar way to the BFR application only. Modifications were observed in BM, BMD and BMC. The ENMS + BFR led the results, improving the BMD and BMC. The walk + BFR showed to improve the BM and the BMD at the same time.The BFR added to the stimuli, ENMS, walk and squat generates positive effects on the MH, MDF and bone tissue of the lower limb. The BFR also generates changes without the association to another stimulus, but to a lesser extent. It was not possible to achieve a statistically significant difference (p > 0.05) between the groups

Ultrasound-Based Phenotyping of Lateral Ventricles to Predict Hydrocephalus Outcome in Premature Neonates.

OBJECTIVE: Prediction of post-hemorrhagic hydrocephalus (PHH) outcome-i.e., whether it requires intervention or not-in premature neonates using cranial ultrasound (CUS) images is challenging. In this paper, we present a novel fully-automatic method to perform phenotyping of the brain lateral ventricles and predict PHH outcome from CUS. METHODS: Our method consists of two parts: ventricle quantification followed by prediction of PHH outcome. First, cranial bounding box and brain interhemispheric fissure are detected to determine the anatomical position of ventricles and correct the cranium rotation. Then, lateral ventricles are extracted using a new deep learning-based method by incorporating the convolutional neural network into a probabilistic atlas-based weighted loss function and an image-specific adaption. PHH outcome is predicted using a support vector machine classifier trained using ventricular morphological phenotypes and clinical information. RESULTS: Experiments demonstrated that our method achieves accurate ventricle segmentation results with an average Dice similarity coefficient of 0.86, as well as very good PHH outcome prediction with accuracy of 0.91. CONCLUSION: Automatic CUS-based ventricular phenotyping in premature newborns could objectively and accurately predict the progression to severe PHH. SIGNIFICANCE: Early prediction of severe PHH development in premature newborns could potentially advance criteria for diagnosis and offer an opportunity for early interventions to improve outcome.

Myo1e modulates the recruitment of activated B cells to inguinal lymph nodes.

The inclusion of lymphocytes in high endothelial venules and their migration to the lymph nodes are critical steps in the immune response. Cell migration is regulated by the actin cytoskeleton and myosins. Myo1e is a long-tailed class I myosin and is highly expressed in B cells, which have not been studied in the context of cell migration. By using intravital microscopy in an in vivo model and performing in vitro experiments, we studied the relevance of Myo1e for the adhesion and inclusion of activated B cells in high endothelial venules. We observed reduced expression of integrins and F-actin in the membrane protrusions of B lymphocytes, which might be explained by deficiencies in vesicular trafficking. Interestingly, the lack of Myo1e reduced the phosphorylation of focal adhesion kinase (FAK; also known as PTK2), AKT (also known as AKT1) and RAC-1, disturbing the FAK-PI3K-RAC-1 signaling pathway. Taken together, our results indicate a critical role of Myo1e in the mechanism of B-cell adhesion and migration.

Randomized controlled trial of a 12-week digital care program in improving low back pain.

Low back pain (LBP) is the leading cause of disability throughout the world and is economically burdensome. The recommended first line treatment for non-specific LBP is non-invasive care. A digital care program (DCP) delivering evidence-based non-invasive treatment for LBP can aid self-management by engaging patients and scales personalized therapy for patient-specific needs. We assessed the efficacy of a 12-week DCP for LBP in a two-armed, pre-registered, randomized, controlled trial (RCT). Participants were included based on self-reported duration of LBP, but those with surgery or injury to the lower back in the previous three months were excluded. The treatment group (DCP) received the 12-week DCP, consisting of sensor-guided exercise therapy, education, cognitive behavioral therapy, team and individual behavioral coaching, activity tracking, and symptom tracking - all administered remotely via an app. The control group received three digital education articles only. All participants maintained access to treatment-as-usual. At 12 weeks, an intention-to-treat analysis showed each primary outcome-Oswestry Disability Index (p < 0.001), Korff Pain (p < 0.001) and Korff Disability (p < 0.001)-as well as each secondary outcome improved more for participants in the DCP group compared to control group. For participants who completed the DCP (per protocol), average improvement in pain outcomes ranged 52-64% (Korff: 48.8-23.4, VAS: 43.6-16.5, VAS impact on daily life: 37.3-13.4; p < 0.01 for all) and average improvement in disability outcomes ranged 31-55% (Korff: 33.1-15, ODI: 19.7-13.5; p < 0.01 for both). Surgical interest significantly reduced in the DCP group. Participants that completed the DCP had an average engagement, each week, of 90%. Future studies will further explore the effectiveness of the DCP for long-term outcomes beyond 12 weeks and for a LBP patient population with possibly greater baseline pain and disability. In conclusion, the DCP resulted in improved LBP outcomes compared to treatment-as-usual and has potential to scale personalized evidence-based non-invasive treatment for LBP patients.

Correction to: Epigallocatechin-3-Gallate Protects and Prevents Paraquat-Induced Oxidative Stress and Neurodegeneration in Knockdown dj-1-ß Drosophila melanogaster.

The original version of this article contained mistakes, and the authors would like to publish this erratum. The "Acknowledgement" section was not included in the aforementioned manuscript.

Epigallocatechin-3-Gallate Protects and Prevents Paraquat-Induced Oxidative Stress and Neurodegeneration in Knockdown dj-1-ß Drosophila melanogaster.

Epigallocatechin-3-gallate (EGCG) is a polyhydroxyphenol constituent of green tea (e.g., Camellia sinensis) with known antioxidant properties. Due to these properties, others have proposed it as a potential therapeutic agent for the treatment of Parkinson's disease (PD). Previously, we demonstrated that EGCG prolonged the lifespan and locomotor activity in wild-type Canton-S flies exposed to the neurotoxicant paraquat (PQ), suggesting neuroprotective properties. Both gene mutations and environmental neurotoxicants (e.g., PQ) are factors involved in the development of PD. Thus, the first aim of this study was to create a suitable animal model of PD, which encompasses both of these factors. To create the model, we knocked down dj-1-ß function specifically in the dopaminergic neurons to generate TH > dj-1-ß-RNAi/+ Drosophila melanogaster flies. Next, we induced neurotoxicity in the transgenic flies with PQ. The second aim of this study was to validate the model by comparing the effects of vehicle, EGCG, and chemicals with known antioxidant and neuroprotective properties in vivo (e.g., propyl gallate and minocycline) on life-span, locomotor activity, lipid peroxidation, and neurodegeneration. The EGCG treatment provided protection and prevention from the PQ-induced reduction in the life-span and locomotor activity and from the PQ-induced increase in lipid peroxidation and neurodegeneration. These effects were augmented in the EGCG-treated flies when compared to the flies treated with either PG or MC. Altogether, these results suggest that the transgenic TH > dj-1-ß-RNAi/+ flies treated with PQ serve as a suitable PD model for screening of potential therapeutic agents.

Effects of a 12-Week Digital Care Program for Chronic Knee Pain on Pain, Mobility, and Surgery Risk: Randomized Controlled Trial.

BACKGROUND: Chronic knee pain, most commonly caused by knee osteoarthritis, is a prevalent condition which in most cases can be effectively treated through conservative, non-surgical care involving exercise therapy, education, psychosocial support, and weight loss. However, most people living with chronic knee pain do not receive adequate care, leading to unnecessary use of opiates and surgical procedures. OBJECTIVE: Assess the efficacy of a remotely delivered digital care program for chronic knee pain. METHODS: We enrolled 162 participants into a randomized controlled trial between January and March 2017. Participants were recruited from participating employers using questionnaires for self-assessment of their knee pain, and randomized into treatment (n=101) and control (n=61) groups. Participants in the treatment group were enrolled in the Hinge Health digital care program for chronic knee pain. This is a remotely delivered, home-based 12-week intervention that includes sensor-guided exercise therapy, education, cognitive behavioral therapy, weight loss, and psychosocial support through a personal coach and team-based interactions. The control group received three education pieces regarding self-care for chronic knee pain. Both groups had access to treatment-as-usual. The primary outcome was the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale and KOOS Physical Function Shortform (KOOS-PS). Secondary outcomes were visual analog scales (VAS) for pain and stiffness respectively, surgery intent, and self-reported understanding of the condition and treatment options. Outcome measures were analyzed by intention to treat (excluding 7 control participants who received the digital care program due to administrative error) and per protocol. RESULTS: In an intent-to-treat analysis the digital care program group had a significantly greater reduction in KOOS Pain compared to the control group at the end of the program (greater reduction of 7.7, 95% CI 3.0 to 12.3, P=.002), as well as a significantly greater improvement in physical function (7.2, 95% CI 3.0 to 11.5, P=.001). This was also reflected in the secondary outcomes VAS pain (12.3, 95% CI 5.4 to 19.1, P<.001) and VAS stiffness (13.4, 95% CI 5.6 to 21.1, P=.001). Participants' self-reported likelihood (from 0% to 100%) of having surgery also reduced more strongly in the digital care program group compared to the control group over the next 1 year (-9.4 percentage points, pp, 95% CI -16.6 to -2.2, P=.01), 2 years (-11.3 pp, 95% CI -20.1 to -2.5, P=.01), and 5 years (-14.6 pp, 95% CI -23.6 to -5.5, P=.002). Interest in surgery (from 0 to 10) also reduced more so in the digital care program compared to control group (-1.0, 95% CI -1.7 to -0.2, P=.01). Participants' understanding of the condition and treatment options (on a scale from 0 to 4) increased more substantially for participants in the digital care program than those in the control group (0.9, 95% CI 0.6 to 1.3, P<.001). In an analysis on participants that completed the intervention (per protocol analysis) all primary and secondary outcomes remained significant at greater effect magnitudes compared to intention to treat, with those completing the program showing a 61% (95% CI 48 to 74) reduction in VAS pain compared to 21% (95% CI 5 to 38) in the control group (P<.001). Accounting for the cost of administering the program, we estimate net cost savings on surgery alone of US $4340 over 1 year and $7900 over 5 years for those participants completing the digital care program compared to those in the control group receiving treatment-as-usual. In an exploratory subgroup analysis including only participants exhibiting clinical symptoms of osteoarthritis the program proved equally effective. CONCLUSIONS: This trial provides strong evidence that a comprehensive 12-week digital care program for chronic knee pain, including osteoarthritis, yields significantly improved outcomes for pain, physical function, stiffness, surgery risk, and understanding of the condition, compared to a control group. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 13307390; http://www.isrctn.com/ISRCTN13307390 (Archived by WebCite at http://www.webcitation.org/6ycwjGL73).

Discordance between mass spectrometry and immunometric IGF-1 assay in pituitary disease: a prospective study.

PURPOSE: Measuring IGF-1, a biomarker for GH activity, is critical to evaluating disordered hypothalamic-pituitary GH axis. Inconsistent IGF-1 measurements among different immunoassays are well documented. We switched from Immulite 2000 immunoassay to narrow-mass-extraction, high-resolution liquid chromatography mass-spectrometry (LC-MS) compliant with recent consensus recommendations on assay standardization. Comparability of these two assays in patients with pituitary disease in a clinical practice setting is not known. We sought to compare IGF-1 levels on Immulite 2000 and LC-MS in samples from naïve and treated patients with secretory and non-secretory pituitary masses. METHODS: We prospectively collected serum samples from 101 patients treated at the Cedars-Sinai Pituitary Center between February 2012 and March 2014. We intentionally recruited more patients with acromegaly or GH deficiency to ensure a clinically representative cohort. Samples were classified as in or out of the respective reference ranges. Bland-Altman analysis was used to assess agreement between assays. RESULTS: Twenty-four percent of samples were classified differently as below, in, or above range. Agreement between the assays was poor overall, with a significant bias for immunoassay reporting higher values than LC-MS. This pattern was also observed in patients with acromegaly and those with ≥ 2 pituitary hormone deficiencies. CONCLUSIONS: IGF-1 results may differ after switching from an older immunoassay to a consensus-compliant assay such as LC-MS. Clinicians should consider the potential impact of assay switching before altering treatment due to discrepant results, particularly in patients monitored over time, such as those with acromegaly and GH deficiency.

Reproducibility of percutaneous nephrolithotomy in the Galdakao-modified supine Valdivia position.

To demonstrate that percutaneous nephrolithotomy (PCNL) in the Galdakao-modified supine Valdivia position can be safely and effectively reproduced by different surgeons. A multicentre retrospective cross-sectional case study on 317 patients was conducted. The centres enrolled were four hospitals from the Spanish National Health System and provided data for consecutive PCNL from January 2008 to December 2010. The patients were divided into two groups: the Galdakao group (134; operated on by the master PCNL surgeon) and the other surgeons group (183; operated on by the other surgeons). The results of the technique were analysed relative to success and complications. Finally, a multivariate analysis introducing the covariates age, gender, BMI, ASA and type of stone was performed (backward stepwise logistic regression). The univariate analysis did not reveal differences in age, gender and ASA scores (p > 0.05) between the Galdakao group and the other surgeons group. The success rate was 80.6 % in the Galdakao group and 72.7 % in the other surgeons group (p = 0.01), and the complication rate was 16.4 and 26.2 %, respectively (p = 0.03). Complications were categorised based on the Clavien classification, and no differences were discovered between the groups (p = 0.19). The logistic regression confirmed only the surgeon and the stone type as independent predictive variables. PCNL in the Galdakao-modified supine Valdivia position is feasible for the use by different urologic surgeons. The results depend on the surgeon's experience, but with specific training and, maybe, selecting the simplest cases at the beginning, it is possible to achieve competitive results.

Digital arthrodesis: current fixation techniques.

Several hammertoe implant devices have recently been introduced in an attempt to provide optimal fixation for proximal interphalangeal joint arthrodesis. This article reviews these implants individually, and discusses their advantages and disadvantages. There is a lack of research with long-term follow-up available for these devices. Percutaneous Kirschner-wire fixation persists as a time-honored and effective method of fixation. The buried Kirschner-wire technique is also an effective, cost-conscious option, with many of the same advantages as newer implantable devices.

Activation of PI3K/mTOR pathway occurs in most adult low-grade gliomas and predicts patient survival.

Recent evidence suggests the Akt-mTOR pathway may play a role in development of low-grade gliomas (LGG). We sought to evaluate whether activation of this pathway correlates with survival in LGG by examining expression patterns of proteins within this pathway. Forty-five LGG tumor specimens from newly diagnosed patients were analyzed for methylation of the putative 5'-promoter region of PTEN using methylation-specific PCR as well as phosphorylation of S6 and PRAS40 and expression of PTEN protein using immunohistochemistry. Relationships between molecular markers and overall survival (OS) were assessed using Kaplan-Meier methods and exact log-rank test. Correlation between molecular markers was determined using the Mann-Whitney U and Spearman Rank Correlation tests. Eight of the 26 patients with methylated PTEN died, as compared to 1 of 19 without methylation. There was a trend towards statistical significance, with PTEN methylated patients having decreased survival (P = 0.128). Eight of 29 patients that expressed phospho-S6 died, whereas all 9 patients lacking p-S6 expression were alive at last follow-up. There was an inverse relationship between expression of phospho-S6 and survival (P = 0.029). There was a trend towards decreased survival in patients expressing phospho-PRAS40 (P = 0.077). Analyses of relationships between molecular markers demonstrated a statistically significant positive correlation between expression of p-S6(235) and p-PRAS40 (P = 0.04); expression of p-S6(240) correlated positively with PTEN methylation (P = 0.04) and negatively with PTEN expression (P = 0.03). Survival of LGG patients correlates with phosphorylation of S6 protein. This relationship supports the use of selective mTOR inhibitors in the treatment of low grade glioma.

Comparison of positron emission tomography/computed tomography imaging and ultrasound in staging and surveillance of head and neck and thyroid cancer.

OBJECTIVES/HYPOTHESIS: Positron emission tomography (PET) combined with cross-sectional computed tomography (CT) is increasingly used for staging and surveillance of cancers in the head and neck region. Ultrasonography (US) is an alternative imaging technique that provides diagnostic information while enabling simultaneous image-guided biopsies. A comparison of these diagnostic modalities in cancer detection is warranted. METHODS: All patients with malignant neoplasms in the head and neck region who were evaluated by both PET/CT and US were reviewed. Diagnostic accuracy rates of PET/CT and US were determined according to whether cytologically or histologically confirmed cancer was present in US-guided fine-needle biopsy or surgical specimens. RESULTS: From October 2004 to December 2007, 42 patients with an ultimately confirmed tissue diagnosis of a head and neck malignancy underwent both neck US and PET/CT. The sensitivity and specificity of US in predicting malignancy in the head and neck was 96.8% and 93.3%, respectively, in those 42 individuals. The positive predictive value (PPV) was 96% and the negative predictive value (NPV) was 93%. In comparison, PET/CT in this group demonstrated a sensitivity of 90.3%, specificity 20%, PPV 70%, and NPV 50%. CONCLUSIONS: PET/CT and US, especially when combined with US-guided fine-needle biopsy, are complementary tools in the detection of cancers of the head and neck. The highly sensitive and specific nature of US, combined with its low cost, low morbidity, availability as an in-office examination, and ability to guide biopsies, warrant consideration of its routine use in the management of head and neck and thyroid cancer patients.