Abstract
Background
Telehealth is an effective option to fight the outbreak of COVID-19. This review aims to systematically characterize the utilization and applications of telehealth during the ...COVID-19 pandemic focusing mainly on technology implementations.
Methods
This study was conducted in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The literature search was conducted in Science Direct, IEEE XPLORE, Scopus, and Web of Science databases from January 2020 until July 2021, with an English language restriction. A quality assessment was based on the Critical Appraisal Skills Programs checklist.
Results
The included studies focused on the implementation of technology for telehealth, multidisciplinary approach, service satisfaction, guidelines, and medical training. They provided illustrative insight into the strategy of telehealth in different medical specialties, such as pediatric gastroenterology, oncology, ophthalmology, and laryngology. Nonsurgical specialties had the greatest number of telehealth visits. Clinicians showed positive attitudes toward the implementation of video telehealth visits; patients report high levels of satisfaction with this care and strong interest in continuing this modality as a significant portion of clinical practice.
Conclusions
This systematic review provided an illustrative insight into the strategy of telehealth for different purposes. According to our findings, telehealth may be used in different medical area with a clear strategy of intervention according to patients’ and doctors’ needs.
Abstract
Background
Many healthcare systems have been unable to deal with Covid-19 without influencing non-Covid-19 patients with pre-existing conditions, risking a paralysis in the medium term. This ...study explores the effects of organizational flexibility on hospital efficiency in terms of the capacity to deliver healthcare services for both Covid-19 and non-Covid-19 patients.
Method
Focusing on Italian health system, a two-step strategy is adopted. First, Data Envelope Analysis is used to assess the capacity of hospitals to address the needs of Covid-19 and non-Covid-19 patients relying on internal resource flexibility. Second, two panel regressions are performed to assess external organizational flexibility, with the involvement in demand management of external operators in the health-care service, examining the impact on efficiency in hospital capacity management.
Results
The overall response of the hospitals in the study was not fully effective in balancing the needs of the two categories of patients (the efficiency score is 0.87 and 0.58, respectively, for Covid-19 and non-Covid-19 patients), though responses improved over time. Furthermore, among the measures providing complementary services in the community, home hospitalization and territorial medicine were found to be positively associated with hospital efficiency (0.1290,
p
< 0.05 and 0.2985,
p
< 0.01, respectively, for non-Covid-19 and Covid-19 patients; 0.0026,
p
< 0.05 and 0.0069,
p
< 0.01, respectively, for non-Covid-19 and Covid-19). In contrast, hospital networks are negatively related to efficiency in Covid-19 patients (-0.1037,
p
< 0.05), while the relationship is not significant in non-Covid-19 patients.
Conclusions
Managing the needs of Covid-19 patients while also caring for other patients requires a response from the entire healthcare system. Our findings could have two important implications for effectively managing health-care demand during and after the Covid-19 pandemic. First, as a result of a naturally progressive learning process, the resource balance between Covid-19 and non-Covid-19 patients improves over time. Second, it appears that demand management to control the flow of patients necessitates targeted interventions that combine agile structures with decentralization. Finally, untested integration models risk slowing down the response, giving rise to significant costs without producing effective results.
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Reported here is the synthesis and biological evaluation of the asialoglycoprotein receptor (ASGP-R) targeted fourth generation poliamidoamine dendrimer (G(4)-PAMAM) loaded with ...sorafenib. The ASGP-R targeted dendrimer was obtained by conjugation of Lactobionic acid (La) to the G(4)-PAMAM dendrimer, followed by acetylation (Ac) of the free amino groups in order to reduce the non-specific interactions with the cell membrane. Moreover, by additionally grafting fluorescein (FITC), it was easy to characterize the internalization pathway and the intracellular fate of the targeted dendrimer Ac-La-G(4)-PAMAM-FITC. In vitro experiments performed on HepG-2 and HLE cell lines, allowed to study the ability of the dendrimers to affect the cell vitality. Confocal microscopy and cytofluorimetric analysis confirmed higher binding and uptake ability of the Ac-La-G(4)-PAMAM-FITC dendrimer in well differentiated and ASGP-R expressing human liver cancer cell line HepG-2 compared non-expressing HLE cells. Ac-La-G(4)-PAMAM-FITC dendrimer loaded with sorafenib was stable and showed sustained sorafenib release. As evidenced by the cytotoxicity studies, sorafenib included in the dendrimer maintained its effectiveness, and was able to produce a longer lasting effect over the time compared to molar equivalent doses of free sorafenib. This new targeted dendrimer appears to be a suitable carrier for the delivery of sorafenib to liver cancer cells expressing ASGP-R.
The aim of this study was to characterize new nanoparticles (NPs) containing chitosan (CS), or CS/cyclodextrin (CDs), and evaluate their potential for the oral delivery of the peptide glutathione ...(GSH). More precisely, NP formulations composed of CS, CS/α-CD and CS/sulphobutyl ether-β-cyclodextrin (SBE
7m-β-CD) were investigated for this application. CS/CD NPs showed particle sizes ranging from 200 to 500
nm. GSH was loaded more efficiently in CS/SBE
7m-β-CD NPs by forming a complex between the tripeptide and the CD. X-ray Photoelectron Spectroscopy (XPS) analysis suggested that GSH is located in the core of CS/SBE
7m-β-CD NPs and that it is almost absent from the NP surface. Release studies performed
in vitro at pH 1.2 and pH 6.8 showed that NP release properties can be modulated by selecting an appropriate CD. Transport studies performed in the frog intestine model confirmed that both CS and CS/CD nanoparticles could induce permeabilization of the intestinal epithelia. However, CS/SBE
7m-β-CD NPs provided absorption-enhancing properties in all segments of the duodenum, whereas CS NPs effect was restricted to the first segment of the duodenum. From the data obtained, we believe that CS/CD nanoparticles might represent an interesting technological platform for the oral administration of small peptides.
The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized ...nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl-
-glycero-3-phosphoethanolamine-
-carboxy(poly(ethylene glycol)-2000). The physical features of the prepared liposomes were established with successive determination of their endothelial permeability across an
model of the blood-brain barrier, constituted by human cerebral microvascular endothelial cells (hCMEC/D3). Functionalized dopamine-loaded liposomes with encapsulation efficiency more than 35% were made with sizes in a range around 180 nm, polydispersity indices of 0.2, and positive zeta potential values (+7.5 mV). Their stability and drug release kinetics were also evaluated. The apparent permeability (P
) values of encapsulated dopamine in functionalized and unfunctionalized liposomes showed that transferrin functionalized nanocarriers could represent appealing non-toxic candidates for brain delivery, thus improving benefits and decreasing complications to patients subjected to L-dopa chronical treatment.
A new fluorine-substituted ligand, compound 1 (CB251), with a very high affinity (Ki = 0.27 ± 0.09 nM) and selectivity for the 18-kDa translocator protein (TSPO), is presented as an attractive ...biomarker for the diagnosis of neuroinflammation, neurodegeneration and tumour progression. To test compound 1 as a TSPO PET imaging agent in vivo, 2-(2-(4-(2-(18)Ffluoroethoxy)phenyl)-6,8-dichloroimidazo1,2-apyridin-3-yl)-N,N-dipropylacetamide ((18)F1; (18)FCB251) was synthesized by nucleophilic aliphatic substitution in a single-step radiolabelling procedure with a 11.1 ± 3.5% (n = 14, decay corrected) radiochemical yield and over 99% radiochemical purity. In animal PET imaging studies, (18)FCB251 provided a clearly visible image of the inflammatory lesion with the binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND 1.83 ± 0.18), in a neuroinflammation rat model based on the unilateral stereotaxic injection of lipopolysaccharide (LPS), comparable to that of (11)CPBR28 (BPND 1.55 ± 0.41). (18)FCB251 showed moderate tumour uptake (1.96 ± 0.11%ID/g at 1 h post injection) in human glioblastoma U87-MG xenografts. These results suggest that (18)FCB251 is a promising TSPO PET imaging agent for neuroinflammation and TSPO-rich cancers.
New scientific findings have recently shown that dasatinib (DAS), the first-choice oral drug in the treatment of chronic myeloid leukemia (CML) for adult patients who are resistant or intolerant to ...imatinib, is also potentially useful in the paediatric age. Moreover, recent preclinical evidences suggest that this drug could be useful for the treatment of Duchenne muscular dystrophy, since it targets cSrc tyrosin kinase. Based on these considerations, the purpose of this work was to use the strategy of complexation with hydroxypropyl-β-cyclodextrin (HP-β-CD) in order to obtain an aqueous preparation of DAS, which is characterized by a low water solubility (6.49 × 10
mg/mL). Complexation studies demonstrated that HP-β-CD is able to form a stable host-guest inclusion complex with DAS with a 1:1 apparent formation constant of 922.13 M
, as also demonstrated by the Job's plot, with an increase in DAS aqueous solubility of about 21 times in the presence of 6%
/
of HP-β-CD (0.014 mg/mL). The inclusion complex has been prepared in the solid state by lyophilization and characterized by Fourier Transform Infrared (FT-IR), Nuclear Magnetic Resonance (NMR), Differential Scanning Calorimetry (DSC) techniques, and its dissolution profile was studied at different pH values. Moreover, in view of potential use of DAS for Duchenne muscular dystrophy, the cytotoxic effect of the inclusion complex has been assessed on C2C12 cells, a murine muscle satellite cell line. In parallel, a one-week oral treatment was performed in wild type C57Bl/6J mice to test both palatability and the exposure levels of the new oral formulation of the compound. In conclusion, this new inclusion complex could allow the development of a liquid and solvent free formulation to be administered both orally and parenterally, especially in the case of an administration in paediatric age.
Translocator protein 18-kDa (TSPO) is a versatile mitochondrial target for molecular imaging and therapy. Moreover, selective TSPO ligands have been widely investigated for diagnostic purposes and ...explored to target drug delivery systems directed to cancer cells overexpressing TSPO. Indeed, poly(d,l-lactic-co-glycolic acid (PLGA) polymers and nanocarriers decorated with TSPO ligands are capable of transporting TSPO ligands inside cancer cells, inducing survival inhibition in cancer cells and producing mitochondrial morphology modification. The aim of this work was to prepare nanogels (NGs) made with TSPO ligand dextran conjugates (TSPO-Dex) that are useful as potential delivery systems of two TSPO ligands as apoptotic agents. Synthesis and complete characterization of TSPO-dextran conjugates, an average molecular weights analysis, TSPO ligand release profiles, thermal behaviour and swelling studies were achieved. NG preparation, characterization and in vitro biological studies were also performed. The release of TSPO ligands released from dextran conjugates at 37 °C occurred in human serum at a faster rate than that detected in phosphate buffer. Cytotoxicity studies demonstrated that NGs produced from TSPO ligand-dextran conjugates induce survival inhibition in rat C6 glioma cell lines. Cellular uptake was also proven by fluorescence microscopy.
The objective of this study was to investigate the role of the oomycete Phytophthora× cambivora in the decline affecting European beech (Fagus sylvatica) in the Nebrodi Regional Park (Sicily, ...southern Italy). In a survey of a beech forest stand in the heart of the park, Phytophthora× cambivora was the sole Phytophthora species recovered from the rhizosphere soil and fine roots of trees. Both A1 and A2 mating type isolates were found. Direct isolation from the stem bark of trees showing severe decline symptoms and bleeding stem cankers yielded exclusively P. gonapodyides, usually considered as an opportunistic pathogen. The mean inoculum density of P.× cambivora in the rhizosphere soil, as determined using the soil dilution plating method and expressed in terms of colony forming units (cfus) per gm of soil, the isolation frequency using leaf baiting, and the percentage of infected fibrous roots from 20 randomly selected beech trees with severe decline symptoms (50 to 100 foliage transparency classes) were 31.7 cfus, 80%, and 48.6%, respectively. These were significantly higher than the corresponding mean values of 20 asymptomatic or slightly declining trees, suggesting P.× cambivora is a major factor responsible for the decline in the surveyed stand.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies, with poor outcomes largely due to its unique microenvironment, which is responsible for the low response to drugs ...and drug-resistance phenomena. This clinical need led us to explore new therapeutic approaches for systemic PDAC treatment by the utilization of two newly synthesized biphenylnicotinamide derivatives, PTA73 and PTA34, with remarkable antitumor activity in an in vitro PDAC model. Given their poor water solubility, inclusion complexes of PTA34 and PTA73 in Hydroxy-Propil-β-Cyclodextrin (HP-β-CD) were prepared in solution and at the solid state. Complexation studies demonstrated that HP-β-CD is able to form stable host-guest inclusion complexes with PTA34 and PTA73, characterized by a 1:1 apparent formation constant of 503.9 M
and 369.2 M
, respectively (also demonstrated by the Job plot), and by an increase in aqueous solubility of about 150 times (from 1.95 µg/mL to 292.5 µg/mL) and 106 times (from 7.16 µg/mL to 762.5 µg/mL), in the presence of 45%
of HP-β-CD, respectively. In vitro studies confirmed the high antitumor activity of the complexed PTA34 and PTA73 towards PDAC cells, the strong G2/M phase arrest followed by induction of apoptosis, and thus their eligibility for PDAC therapy.
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