Abstract
Objective
The purpose of this article was to summarize the available evidence from systematic reviews on telerehabilitation in physical therapy.
Methods
We searched Medline/PubMed, EMBASE, ...and Cochrane Library databases. In addition, the records in PROSPERO and Epistemonikos and PEDro were consulted. Systematic reviews of different conditions, populations, and contexts—where the intervention to be evaluated is telerehabilitation by physical therapy—were included. The outcomes were clinical effectiveness depending on specific condition, functionality, quality of life, satisfaction, adherence, and safety. Data extraction and risk of bias assessment were carried out by a reviewer with non-independent verification by a second reviewer. The findings are reported qualitatively in the tables and figures.
Results
Fifty-three systematic reviews were included, of which 17 were assessed as having low risk of bias. Fifteen reviews were on cardiorespiratory rehabilitation, 14 on musculoskeletal conditions, and 13 on neurorehabilitation. The other 11 reviews addressed other types of conditions and rehabilitation. Thirteen reviews evaluated with low risk of bias showed results in favor of telerehabilitation versus in-person rehabilitation or no rehabilitation, while 17 reported no differences between the groups. Thirty-five reviews with unclear or high risk of bias showed mixed results.
Conclusions
Despite the contradictory results, telerehabilitation in physical therapy could be comparable with in-person rehabilitation or better than no rehabilitation for conditions such as osteoarthritis, low-back pain, hip and knee replacement, and multiple sclerosis and also in the context of cardiac and pulmonary rehabilitation. It is imperative to conduct better quality clinical trials and systematic reviews.
Impact
Providing the best available evidence on the effectiveness of telerehabilitation to professionals, mainly physical therapists, will impact the decision-making process and therefore yield better clinical outcomes for patients, both in these times of the COVID-19 pandemic and in the future. The identification of research gaps will also contribute to the generation of relevant and novel research questions.
Purpose This phase III study evaluated ribociclib plus fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer who were ...treatment naïve or had received up to one line of prior endocrine therapy in the advanced setting. Patients and Methods Patients were randomly assigned at a two-to-one ratio to ribociclib plus fulvestrant or placebo plus fulvestrant. The primary end point was locally assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. Results A total of 484 postmenopausal women were randomly assigned to ribociclib plus fulvestrant, and 242 were assigned to placebo plus fulvestrant. Median progression-free survival was significantly improved with ribociclib plus fulvestrant versus placebo plus fulvestrant: 20.5 months (95% CI, 18.5 to 23.5 months) versus 12.8 months (95% CI, 10.9 to 16.3 months), respectively (hazard ratio, 0.593; 95% CI, 0.480 to 0.732; P < .001). Consistent treatment effects were observed in patients who were treatment naïve in the advanced setting (hazard ratio, 0.577; 95% CI, 0.415 to 0.802), as well as in patients who had received up to one line of prior endocrine therapy for advanced disease (hazard ratio, 0.565; 95% CI, 0.428 to 0.744). Among patients with measurable disease, the overall response rate was 40.9% for the ribociclib plus fulvestrant arm and 28.7% for placebo plus fulvestrant. Grade 3 adverse events reported in ≥ 10% of patients in either arm (ribociclib plus fulvestrant v placebo plus fulvestrant) were neutropenia (46.6% v 0%) and leukopenia (13.5% v 0%); the only grade 4 event reported in ≥ 5% of patients was neutropenia (6.8% v 0%). Conclusion Ribociclib plus fulvestrant might represent a new first- or second-line treatment option in hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer.
•TCDD induces toxicity in SHSY5Y human neuroblastoma cells.•TCDD toxicity in SHSY5Y neuroblastoma cells depends on dioxin concentration and time of incubation.•Transient transfection of a hairpin RNA ...for AhR protects against TCDD neurotoxicity.
2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a xenobiotic agent with high persistency that induces neurotoxic effects altering neurodevelopment and behavior. The molecular mechanisms and the signaling pathways involved in TCDD-mediated neurotoxicity, together with the search of its molecular targets in neurons are under intense study. We have previously shown that high nanomolar concentrations of TCDD for incubation times of minutes induce apoptosis in SHSY5Y human neuroblastoma cells by the disruption of calcium homeostasis, affecting membrane structural integrity. In this work, we have analyzed the effect of low nanomolar concentrations of TCDD for incubation times of hours to define the role of aryl hydrocarbon receptor which can be activated at those concentrations. TCDD induces toxicity in SHSY5Y human neuroblastoma cells under these experimental conditions with an EC50 value of approximately 3nM at 24h of incubation time. Transient transfection of a hairpin RNA for AhR protects against TCDD neurotoxicity, suggesting that AhR is mediating the dioxin effect. Altogether, these results support the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma cells depends on dioxin concentration and time of incubation, with a main role of aryl hydrocarbon receptor at low nanomolar TCDD concentrations.
Parkinson’s disease (PD) is a slowly progressive neurodegenerative disorder, characterized by the misfolding and aggregation of α-synuclein (α-syn) into Lewy bodies and the degeneration of ...dopaminergic neurons in the substantia nigra pars compacta. The urge for an early diagnosis biomarker comes from the fact that clinical manifestations of PD are estimated to appear once the substantia nigra has deteriorated and there has been a reduction of the dopamine levels from the striatum. Nowadays, extracellular vesicles (EVs) play an important role in the pathogenesis of neuro-degenerative diseases as PD. A systematic review dated August 2022 was carried out with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses with the aim to analyze the potential role of EVs as biomarkers for PD. From a total of 610 articles retrieved, 29 were eligible. This review discusses the role of EVs biochemistry and their cargo proteins, such as α-syn and DJ-1 among others, detected by a proteomic analysis as well as miRNAs and lncRNAs, as potential biomarkers that can be used to create standardized protocols for early PD diagnosis as well as to evaluate disease severity and progression.
In eukaryotes, DNA polymerase δ (Pol δ) bound to the proliferating cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (FEN1) to process the Okazaki ...fragments for their ligation. We present the high-resolution cryo-EM structure of the human processive Pol δ-DNA-PCNA complex in the absence and presence of FEN1. Pol δ is anchored to one of the three PCNA monomers through the C-terminal domain of the catalytic subunit. The catalytic core sits on top of PCNA in an open configuration while the regulatory subunits project laterally. This arrangement allows PCNA to thread and stabilize the DNA exiting the catalytic cleft and recruit FEN1 to one unoccupied monomer in a toolbelt fashion. Alternative holoenzyme conformations reveal important functional interactions that maintain PCNA orientation during synthesis. This work sheds light on the structural basis of Pol δ's activity in replicating the human genome.
In patients with ischemic cardiomyopathy and an implantable cardioverter-defibrillator (ICD), catheter ablation and antiarrhythmic drugs (AADs) reduce ICD shocks, but the most effective approach ...remains uncertain.
This trial compares the efficacy and safety of catheter ablation vs AAD as first-line therapy in ICD patients with symptomatic ventricular tachycardias (VTs).
The SURVIVE-VT (Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia) is a prospective, multicenter, randomized trial including patients with ischemic cardiomyopathy and appropriated ICD shock. Patients were 1:1 randomized to complete endocardial substrate-based catheter ablation or antiarrhythmic therapy (amiodarone + beta-blockers, amiodarone alone, or sotalol ± beta-blockers). The primary outcome was a composite of cardiovascular death, appropriate ICD shock, unplanned hospitalization for worsening heart failure, or severe treatment-related complications.
In this trial, 144 patients (median age, 70 years; 96% male) were randomized to catheter ablation (71 patients) or AAD (73 patients). After 24 months, the primary outcome occurred in 28.2% of patients in the ablation group and 46.6% of those in the AAD group (hazard ratio HR: 0.52; 95% CI: 0.30-0.90; P = 0.021). This difference was driven by a significant reduction in severe treatment-related complications (9.9% vs 28.8%, HR: 0.30; 95% CI: 0.13-0.71; P = 0.006). Eight patients were hospitalized for heart failure in the ablation group and 13 in the AAD group (HR: 0.56; 95% CI: 0.23-1.35; P = 0.198). There was no difference in cardiac mortality (HR: 0.93; 95% CI: 0.19-4.61; P = 0.929).
In ICD patients with ischemic cardiomyopathy and symptomatic VT, catheter ablation reduced the composite endpoint of cardiovascular death, appropriate ICD shock, hospitalization due to heart failure, or severe treatment-related complications compared to AAD. (Substrate Ablation vs Antiarrhythmic Drug Therapy for Symptomatic Ventricular Tachycardia SURVIVE-VT: NCT03734562)
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An earlier report documented significant improvement in progression-free survival among patients with metastatic breast cancer treated with fulvestrant and a cyclin-dependent kinase inhibitor, ...ribociclib. With longer follow-up, it is clear that fulvestrant and ribociclib also prolong overall survival.
This paper evaluates Integrated Multi-Satellite Retrievals from GPM (IMERG-F) over Europe for the period 2014–2018 in order to evaluate application of the retrievals to hydrology. IMERG-F is compared ...with a large pan-European precipitation dataset built on rain gauge stations, i.e., the ENSEMBLES OBServation (E-OBS) gridded dataset. Although there is overall agreement in the spatial distribution of mean precipitation (R2 = 0.8), important discrepancies are revealed in mountainous regions, specifically the Alps, Pyrenees, west coast of the British Isles, Scandinavia, the Iberian and Italian peninsulas, and the Adriatic coastline. The results show that the strongest contributors to poor performance are pixels where IMERG-F has no gauges available for adjustment. If rain gauges are available, IMERG-F yields results similar to those of the surface observations, although the performance varies by region. However, even accounting for gauge adjustment, IMERG-F systematically underestimates precipitation in the Alps and Scandinavian mountains. Conversely, IMERG-F overestimates precipitation in the British Isles, Italian Peninsula, Adriatic coastline, and eastern European plains. Additionally, the research shows that gauge adjustment worsens the spatial gradient of precipitation because of the coarse resolution of Global Precipitation Climatology Centre data.
The flagellate protozoan Giardia duodenalis is an enteric parasite causing human giardiasis, a major gastrointestinal disease of global distribution affecting both developing and industrialised ...countries. In Spain, sporadic cases of giardiasis have been regularly identified, particularly in pediatric and immigrant populations. However, there is limited information on the genetic variability of circulating G. duodenalis isolates in the country.
In this longitudinal molecular epidemiological study we report the diversity and frequency of the G. duodenalis assemblages and sub-assemblages identified in 199 stool samples collected from 184 individual with symptoms compatible with giardiasis presenting to two major public hospitals in Madrid for the period December 2013-January 2015. G. duodenalis cysts were initially detected by conventional microscopy and/or immunochomatography on stool samples. Confirmation of the infection was performed by direct immunofluorescence and real-time PCR methods. G. duodenalis assemblages and sub-assemblages were determined by multi-locus genotyping of the glutamate dehydrogenase (GDH) and β-giardin (BG) genes of the parasite. Sociodemographic and clinical features of patients infected with G. duodenalis were also analysed.
Of 188 confirmed positive samples from 178 giardiasis cases a total of 124 G. duodenalis isolates were successfully typed at the GDH and/or the BG loci, revealing the presence of sub-assemblages BIV (62.1%), AII (15.3%), BIII (4.0%), AI (0.8%), and AIII (0.8%). Additionally, 6.5% of the isolates were only characterised at the assemblage level, being all of them assigned to assemblage B. Discordant genotype results AII/AIII or BIII/BIV were also observed in 10.5% of DNA isolates. A large number of multi-locus genotypes were identified in G. duodenalis assemblage B, but not assemblage A, isolates at both the GDH and BG loci, confirming the high degree of genetic variability observed in other molecular surveys. BIV was the most prevalent genetic variant of G. duodenalis found in individuals with symptomatic giardiasis in the population under study.
Human giardiasis is an ongoing public health problem in Spain affecting primarily young children under four years of age but also individuals of all age groups. Our typing and sub-typing results demonstrate that assemblage B is the most prevalent G. duodenalis assemblage circulating in patients with clinical giardiasis in Central Spain. Our analyses also revealed a large genetic variability in assemblage B (but not assemblage A) isolates of the parasite, corroborating the information obtained in similar studies in other geographical regions. We believe that molecular data presented here provide epidemiological evidence at the population level in support of the existence of genetic exchange within assemblages of G. duodenalis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
It has not been determined whether ileal appearance differs among dogs with chronic inflammatory enteropathy (CIE) and different serum concentrations of cobalamin.
Objective
To compare ...endoscopic and histologic ileal findings in dogs with CIE and different serum cobalamin concentrations and then evaluate the correlation of ileal changes to cobalamin serum concentration using updated scoring systems to assess the ileum.
Animals
Sixty‐eight dogs with CIE.
Methods
Retrospective study. Frequency of ileal features and ileal histologic and endoscopic scores (IHS and IES) were obtained and compared among CIE dogs with severe hypocobalaminemia (SHC; <200 ng/L), hypocobalaminemia (HC; 200‐350 ng/L), or normocobalaminemia (NC; >350 ng/L). The correlation of IHS and IES with cobalamin was evaluated.
Results
Friability, villus atrophy, crypt dilatation, epithelial injury, and intraepithelial lymphocytes were more frequent in SHC than in NC dogs (all P ≤ .01). Median SHC‐IES (2; range, 0‐4) was higher than NC‐IES (1; range, 0‐5; P = .004). Median SHC‐IHS (6; range, 3‐9) was higher than HC‐IHS (4; range, 1‐7; P < .001) and NC‐IHS (3; range, 1‐8; P < .001). Cobalamin concentration correlated negatively with IES (ρ = −.34, P = .005) and IHS (ρ = −.58, P < .001).
Conclusions and Clinical Importance
Ileal features and involvement degree markedly differed when cobalamin was <200 or >350 ng/L in CIE dogs. With updated scales to assess the mucosa, greater ileal damage was associated with lower serum cobalamin concentration.
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