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1.
Artigo em Inglês | MEDLINE | ID: mdl-35564673

RESUMO

Medication therapy management (MTM) is provided by pharmacists and other healthcare providers, improves patient health status, and increases the collaboration of MTM providers with others. However, little is known about pharmacists' intention to provide MTM services in Saudi Arabia. This study aimed to predict the pharmacists' willingness in this nation to commit to providing MTM services there. This study used a cross-sectional questionnaire based on the theory of planned behaviour (TPB). The survey was distributed to 149 pharmacists working in hospital and community pharmacies. It included items measuring pharmacist attitudes, intentions, subjective norms, perceived behavioural control, knowledge about the provision of MTM services, and other sociodemographic and pharmacy practice-related items. The pharmacists had a positive attitude towards MTM services (mean = 6.15 ± 1.12) and strong intention (mean = 6.09 ± 1.15), highly perceived social pressure to provide those services (mean = 5.42 ± 1.03), strongly perceived control over providing those services (mean = 4.98 ± 1.05), and had good MTM knowledge (mean = 5.03 ± 1.00). Pharmacists who completed a pharmacy residency programme and had good knowledge of MTM services and a positive attitude towards them usually strongly intended to provide MTM services. Thus, encouraging pharmacists to complete pharmacy residency programmes and educating them about the importance and provision of MTM services will enhance their motivation to provide them.

2.
Ann Med Surg (Lond) ; : 103772, 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35573470

RESUMO

India, the second most populous country in the world, started its mass vaccination campaign on January 16th 2021. With the aim to vaccinate 1.3 billion people, this vaccination programme was dubbed as the world's largest vaccination drive. However, with depleted blood stores due to the COVID-19 pandemic and lockdown leading to reduced blood camps, the superposed regulations on blood donation deferral poses an impending risk of depletion of blood and its products. This will lead to the inability in meeting unpredictable patterns of demand in blood requirement post-pandemic. Hence to prevent avoidable risks of blood shortage in surgeries and lifesaving procedures, a secure storage system should be ensured.

3.
J Biomol Struct Dyn ; : 1-12, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35510619

RESUMO

The coronavirus disease (COVID-19) pandemic has rapidly extended globally and killed approximately 5.83 million people all over the world. But, to date, no effective therapeutic against the disease has been developed. The disease is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enters the host cell through the spike glycoprotein (S protein) of the virus. Subsequently, RNA-dependent RNA polymerase (RdRp) and main protease (Mpro) of the virus mediate viral transcription and replication. Mechanistically inhibition of these proteins can hinder the transcription as well as replication of the virus. Recently oxysterols and its derivative, such as 25 (S)-hydroxycholesterol (25-HC) has shown antiviral activity against SARS-CoV-2. But the exact mechanisms and their impact on RdRp and Mpro have not been explored yet. Therefore, the study aimed to identify the inhibitory activity of 25-HC against the viral enzymes RdRp and Mpro simultaneously. Initially, a molecular docking simulation was carried out to evaluate the binding activity of the compound against the two proteins. The pharmacokinetics (PK) and toxicity parameters were analyzed to observe the 'drug-likeness' properties of the compound. Additionally, molecular dynamics (MD) simulation was performed to confirm the binding stability of the compound to the targeted protein. Furthermore, molecular mechanics generalized Born surface area (MM-GBSA) was used to predict the binding free energies of the compound to the targeted protein. Molecular docking simulation identified low glide energy -51.0 kcal/mol and -35.0 kcal/mol score against the RdRp and Mpro, respectively, where MD simulation found good binding stability of the compound to the targeted proteins. In addition, the MM/GBSA approach identified a good value of binding free energies (ΔG bind) of the compound to the targeted proteins. Therefore, the study concludes that the compound 25-HC could be developed as a treatment and/or prevention option for SARS-CoV-2 disease-related complications. Although, experimental validation is suggested for further evaluation of the work.Communicated by Ramaswamy H. Sarma.

4.
Bioorg Chem ; 125: 105850, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35533581

RESUMO

Nucleoside precursors and nucleoside analogs occupy an important place in the treatment of viral respiratory pathologies, especially during the current COVID-19 pandemic. From this perspective, the present study has been designed to explore and evaluate the synthesis and spectral characterisation of 5́-O-(lauroyl) thymidine analogs 2-6 with different aliphatic and aromatic groups through comprehensive in vitro antimicrobial screening, cytotoxicity assessment, physicochemical aspects, molecular docking and molecular dynamics analysis, along with pharmacokinetic prediction. A unimolar one-step lauroylation of thymidine under controlled conditions furnished the 5́-O-(lauroyl) thymidine and indicated the selectivity at C-5́ position and the development of thymidine based potential antimicrobial analogs, which were further converted into four newer 3́-O-(acyl)-5́-O-(lauroyl) thymidine analogs in reasonably good yields. The chemical structures of the newly synthesised analogs were ascertained by analysing their physicochemical, elemental, and spectroscopic data. In vitro antimicrobial tests against five bacteria and two fungi, along with the prediction of activity spectra for substances (PASS), indicated promising antibacterial functionality for these thymidine analogs compared to antifungal activity. In support of this observation, molecular docking experiments have been performed against the main protease of SARS-CoV-2, and significant binding affinities and non-bonding interactions were observed against the main protease (6LU7, 6Y84 and 7BQY), considering hydroxychloroquine (HCQ) as standard. Moreover, the 100 ns molecular dynamics simulation process was performed to monitor the behaviour of the complex structure formed by the main protease under in silico physiological conditions to examine its stability over time, and this revealed a stable conformation and binding pattern in a stimulating environment of thymidine analogs. Cytotoxicity determination confirmed that compounds were found less toxic. Pharmacokinetic predictions were investigated to evaluate their absorption, distribution, metabolism and toxic properties, and the combination of pharmacokinetic and drug-likeness predictions has shown promising results in silico. The POM analysis shows the presence of an antiviral (O1δ-, O2δ-) pharmacophore site. Overall, the current study should be of great help in the development of thymidine-based, novel, multiple drug-resistant antimicrobial and COVID-19 drugs.

5.
Cell Rep ; 39(6): 110801, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35545038

RESUMO

Motor cortex generates descending output necessary for executing a wide range of limb movements. Although movement-related activity has been described throughout motor cortex, the spatiotemporal organization of movement-specific signaling in deep layers remains largely unknown. Here we record layer 5B population dynamics in the caudal forelimb area of motor cortex while mice perform a forelimb push/pull task and find that most neurons show movement-invariant responses, with a minority displaying movement specificity. Using cell-type-specific imaging, we identify that invariant responses dominate pyramidal tract (PT) neuron activity, with a small subpopulation representing movement type, whereas a larger proportion of intratelencephalic (IT) neurons display movement-type-specific signaling. The proportion of IT neurons decoding movement-type peaks prior to movement initiation, whereas for PT neurons, this occurs during movement execution. Our data suggest that layer 5B population dynamics largely reflect movement-invariant signaling, with information related to movement-type being routed through relatively small, distributed subpopulations of projection neurons.

6.
Front Mol Biosci ; 9: 864286, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547394

RESUMO

Among the nitrogen-containing heterocyclic compounds, triazoles emerge with superior pharmacological applications. Structurally, there are two types of five-membered triazoles: 1,2,3-triazole and 1,2,4-triazole. Due to the structural characteristics, both 1,2,3- and 1,2,4-triazoles are able to accommodate a broad range of substituents (electrophiles and nucleophiles) around the core structures and pave the way for the construction of diverse novel bioactive molecules. Both the triazoles and their derivatives have significant biological properties including antimicrobial, antiviral, antitubercular, anticancer, anticonvulsant, analgesic, antioxidant, anti-inflammatory, and antidepressant activities. These are also important in organocatalysis, agrochemicals, and materials science. Thus, they have a broad range of therapeutic applications with ever-widening future scope across scientific disciplines. However, adverse events such as hepatotoxicity and hormonal problems lead to a careful revision of the azole family to obtain higher efficacy with minimum side effects. This review focuses on the structural features, synthesis, and notable therapeutic applications of triazoles and related compounds.

7.
BMC Ophthalmol ; 22(1): 210, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534801

RESUMO

PURPOSE: To evaluate the visual outcome, intraocular pressure control and trabeculectomy survival after phacoemulsification in eyes with prior trabeculectomy in uveitis associated with Vogt-Koyanagi-Harada disease (VKH). DESIGN: Retrospective comparative study. METHODS: Eyes with uveitic glaucoma associated with VKH who underwent mitomycin C (MMC)-enhanced trabeculectomy were included. Eyes were divided into two groups: the first study group included eyes that later underwent cataract surgery in the form of phacoemulsification, and the second control group included eyes that did not have cataract surgery. The main outcome measures were changes in the visual acuity, intraocular pressure (IOP), the number of antiglaucoma medications, IOP control and trabeculectomy survival. RESULTS: There were no significant differences in the final visual acuity (0.78 (±0.9) and 0.92 (±1.1), p = 0.80)) nor IOP (14.21 mmHg (±5.8) and 12.16 mmHg (±6.1), p = 0.29), but there was a difference in the antiglaucoma medications (1.58 (±1.5) and 0.53 (±1.0), p = 0.02) between the study and control group, respectively. There was no difference in the overall trabeculectomy survival (p = 0.381, Log Rank), but more eyes in the study group converted to qualified success after phacoemulsification and required more medications to control the IOP. CONCLUSION: Phacoemulsification after trabeculectomy seems to be a safe procedure in eyes with combined vision threatening complications of VKH, although the visual improvement was limited. Nevertheless, more medications were required to control the IOP, resulting in less absolute and more qualified trabeculectomy success. Therefore, patient counseling before surgery is essential.


Assuntos
Catarata , Facoemulsificação , Trabeculectomia , Uveíte , Síndrome Uveomeningoencefálica , Catarata/complicações , Humanos , Pressão Intraocular , Mitomicina , Facoemulsificação/métodos , Estudos Retrospectivos , Trabeculectomia/métodos , Resultado do Tratamento , Uveíte/complicações , Uveíte/cirurgia , Síndrome Uveomeningoencefálica/complicações
8.
J Family Med Prim Care ; 11(3): 1070-1076, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35495803

RESUMO

Background: Nasal decongestant drugs are widely used as potent vasoconstrictive agents to reduce congestion of nasal and ocular mucous membranes in disease such as allergic rhinitis. These drugs are easily accessible to the people over the counter without prescription. The ease in access may lead the population in believing that the drugs are risk free and free from side effects. The purpose of this study was to determine the level of awareness of the people in Unaizah Al-Qassim province in Saudi Arabia on the use of nasal decongestants ad their side effects. Methodology: After gaining the Institutional Review Board (IRB) approval, the study was a questionnaire-based cross-sectional study conducted on the people Unaizah Al-Qassim province in Saudi Arabia. It was explorative in nature as such a study has never been done in Unaizah before and hence descriptive statistics was mainly used to establish significance and reference. The questionnaires assessed the demographical characteristics of the population, participants' history on the usage of nasal decongestants, health condition of the participants, and knowledge on nasal congestion and use nasal decongestants. Results: Out of 385 participants, 54% were male and 46% are female. With regards to age, majority of the participants were between the age of 20 and 40 years 56%, followed by 40--60 years old (33%). 79% of the participants had acquired a baccalaureus level in education. When assessed on the usage of nasal decongestants, 32.5% currently use the decongestants, 64.4% have ever used the drugs now and in the past. In terms of knowledge of the drugs, 16.6% of the participants are aware of the side effects, 25.2% are aware of the medically recommended period to use the drugs, 21.3% have heard of the nasal congestion addiction, and 21.6% are aware of the medication that may cause nasal congestion. Conclusion: The study established that the level of awareness on the use nasal decongestants and the side effects is not significant. There needs to be a sensitization campaign to educate the population on the use of nasal decongestants.

9.
Am J Clin Dermatol ; 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35503163

RESUMO

BACKGROUND: Moderate-to-severe atopic dermatitis (AD) often requires long-term management with systemic therapies. OBJECTIVE: Our objective was to report the safety and efficacy of dupilumab treatment up to 4 years in adults with moderate-to-severe AD and efficacy in a subgroup of patients who transitioned from dupilumab once-weekly (qw) to administration every other week (q2w). METHODS: This interim analysis of the open-label extension study (NCT01949311) evaluated dupilumab 300 mg qw or q2w in adults previously enrolled in dupilumab trials for moderate-to-severe AD. Patients switched from qw to q2w following protocol amendment. The primary outcome was safety; efficacy was also assessed. RESULTS: Of 2677 patients enrolled and treated, 352 (13.1%) completed week 204 (end of efficacy assessments) and 202 (7.5%) completed safety follow-up through week 244. Self-reported compliance was 98.1%. Dupilumab's safety profile was consistent with previous reports. Common treatment-emergent adverse events (≥5%) included nasopharyngitis, AD, upper respiratory tract infection, oral herpes, conjunctivitis, injection-site reaction, and headache. At week 204, mean ± standard deviation (SD) Eczema Area and Severity Index was 2.46 ± 3.98, and mean percent change from parent study baseline (PSBL) was -91.07%; mean ± SD Pruritus Numerical Rating Scale score was 2.10 ± 1.83, and mean percent change from PSBL was -68.74%. Efficacy was maintained in patients (n = 226) who transitioned from qw to q2w dosing. Limitations of this study included its open-label design, the lack of control arm, and smaller subsets of patients at later timepoints and receiving the approved q2w regimen. CONCLUSION: These results support dupilumab as continuous long-term treatment for adults with moderate-to-severe AD; efficacy was sustained following transition from qw to q2w dosing. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT01949311.


Atopic dermatitis is a chronic skin disease associated with inflamed skin and intense itching. People with moderate-to-severe atopic dermatitis often need long-term treatment, but many available treatments do not have demonstrated long-term safety data. In multiple clinical trials, dupilumab treatment resulted in significant improvements in signs and symptoms of atopic dermatitis. This study examined the safety and efficacy of up to 4 years of dupilumab treatment in adults with moderate-to-severe atopic dermatitis, and whether dupilumab continued to be effective in patients who switched from receiving treatment each week to treatment every other week. To address these questions, we collected data from adults who received 300 milligrams of dupilumab every week or every other week. In this study, safety findings were consistent with the known dupilumab safety profile. Patients' signs and symptoms were evaluated before and during treatment with evaluation tools including the Eczema Area and Severity Index (EASI), which indicates the extent and severity of disease, and the Pruritus Numerical Rating Scale (NRS), which indicates the intensity of itching. Reductions of 91% in EASI scores and 69% in Pruritus NRS scores showed that the improvement in signs and symptoms persisted for 204 weeks (almost 4 years) of treatment, and these effects were sustained following the switch from weekly treatment to the approved every other week treatment with dupilumab. The safety and efficacy data presented here support the use of dupilumab as a continuous, long-term treatment for up to 4 years for adults with moderate-to-severe atopic dermatitis.

10.
Microsc Res Tech ; 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35421274

RESUMO

The purpose of this study was to introduce antibacterial property to pits and fissure sealant (PFS) in order to mitigate the major clinical problems associated with PFS, such as microleakage and secondary caries. We prepared a pH reliant cobalt oxide nanoparticle incorporated with minocycline (MNC@CO) and characterized to investigate its antibacterial potential against Streptococcus sobrinus. The physiochemical, morphological, and drug release kinetics at different pH (7.4, 5.0, and 3.5) from nanoparticles were investigated. The MNC@CO were added at 2.5% and 5.0% into experimental PFS and characterized for their antibiofilm capacity, biocompatibility, and mechanical properties including compressive and flexural strength. The groups 2.5% and 5.0% has shown statistically significant antimicrobial capacity against S. sobrinus compared to control (p < .05). The highest percentage of MNC release at different pH (especially at pH 5.0 and 3.5) was observed from 5.0% MNC@CO doped PFS. The PFS doped with 2.5% MNC@CO showed a highest compressive strength (110 MPa) over a period of 70 days as compared to 5.0% MNC@CO (75 MPa) and control (80 MPa). The flexural strength of both experimental groups was lower for both time points (24 h and 30 days) than control. In conclusion, the present study found that 2.5% MNC@CO doped PFS showed considerable anti-biofilm potential without compromising mechanical properties.

11.
JMIR Med Educ ; 8(2): e34973, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35412463

RESUMO

BACKGROUND: Similar to understanding how blood pressure is measured by a sphygmomanometer, physicians will soon have to understand how an artificial intelligence-based application has come to the conclusion that a patient has hypertension, diabetes, or cancer. Although there are an increasing number of use cases where artificial intelligence is or can be applied to improve medical outcomes, the extent to which medical doctors and students are ready to work and leverage this paradigm is unclear. OBJECTIVE: This research aims to capture medical students' and doctors' level of familiarity toward artificial intelligence in medicine as well as their challenges, barriers, and potential risks linked to the democratization of this new paradigm. METHODS: A web-based questionnaire comprising five dimensions-demographics, concepts and definitions, training and education, implementation, and risks-was systematically designed from a literature search. It was completed by 207 participants in total, of which 105 (50.7%) medical doctors and 102 (49.3%) medical students trained in all continents, with most of them in Europe, the Middle East, Asia, and North America. RESULTS: The results revealed no significant difference in the familiarity of artificial intelligence between medical doctors and students (P=.91), except that medical students perceived artificial intelligence in medicine to lead to higher risks for patients and the field of medicine in general (P<.001). We also identified a rather low level of familiarity with artificial intelligence (medical students=2.11/5; medical doctors=2.06/5) as well as a low attendance to education or training. Only 2.9% (3/105) of medical doctors attended a course on artificial intelligence within the previous year, compared with 9.8% (10/102) of medical students. The complexity of the field of medicine was considered one of the biggest challenges (medical doctors=3.5/5; medical students=3.8/5), whereas the reduction of physicians' skills was the most important risk (medical doctors=3.3; medical students=3.6; P=.03). CONCLUSIONS: The question is not whether artificial intelligence will be used in medicine, but when it will become a standard practice for optimizing health care. The low level of familiarity with artificial intelligence identified in this study calls for the implementation of specific education and training in medical schools and hospitals to ensure that medical professionals can leverage this new paradigm and improve health outcomes.

16.
Artigo em Inglês | MEDLINE | ID: mdl-35474519

RESUMO

Ramadan is the ninth month of the Islamic lunar calendar in which it is compulsory for Muslims to abstain from eating and drinking during the daytime. The COVID-19 pandemic posed additional challenges for Muslims as the crowded religious gatherings could give a new breath to the spread of the virus. Similar measures were adopted during Ramadan in 2021. The initiation of COVID-19 vaccination across the globe in combination with the need to maintain personal protective measures against COVID-19, result in new needs and challenges. At this juncture, Ramadan 2022 offers a growing opportunity to unite a global voice for solidarity, equal distribution of COVID-19 vaccines, and tackling the challenge of vaccine hesitancy.

18.
Case Rep Psychiatry ; 2022: 4943485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360258

RESUMO

Individuals with intellectual disability (ID) experience various psychiatric comorbidities including anxiety, depression, and obsessive-compulsive disorder (OCD) in a rate that is equivalent or higher than individuals without ID. Unfortunately, these cooccurring conditions are often missed during the evaluations due to various reasons, including their atypical presentation. In this case report, we present the clinical symptoms of an adolescent with mild ID who presented with irritability and was diagnosed with OCD following a comprehensive assessment. The treatment course is also summarized as well as the positive outcome to selective serotonin reuptake inhibitor (SSRI) medication. In this report, we discuss potential factors that increase the rate of psychiatric comorbidities including OCD in individuals with ID. Furthermore, in the context of limited research in this area, we recommend additional studies in order to build a detailed understanding of the clinical presentation of psychiatric cooccurring disorders in individuals with ID with the goal of enhancing assessment tools in the future.

19.
EClinicalMedicine ; 45: 101317, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35265823

RESUMO

Background: COVID-19 is typically characterised by a triad of symptoms: cough, fever and loss of taste and smell, however, this varies globally. This study examines variations in COVID-19 symptom profiles based on underlying chronic disease and geographical location. Methods: Using a global online symptom survey of 78,299 responders in 190 countries between 09/04/2020 and 22/09/2020, we conducted an exploratory study to examine symptom profiles associated with a positive COVID-19 test result by country and underlying chronic disease (single, co- or multi-morbidities) using statistical and machine learning methods. Findings: From the results of 7980 COVID-19 tested positive responders, we find that symptom patterns differ by country. For example, India reported a lower proportion of headache (22.8% vs 47.8%, p<1e-13) and itchy eyes (7.3% vs. 16.5%, p=2e-8) than other countries. As with geographic location, we find people differed in their reported symptoms if they suffered from specific chronic diseases. For example, COVID-19 positive responders with asthma (25.3% vs. 13.7%, p=7e-6) were more likely to report shortness of breath compared to those with no underlying chronic disease. Interpretation: We have identified variation in COVID-19 symptom profiles depending on geographic location and underlying chronic disease. Failure to reflect this symptom variation in public health messaging may contribute to asymptomatic COVID-19 spread and put patients with chronic diseases at a greater risk of infection. Future work should focus on symptom profile variation in the emerging variants of the SARS-CoV-2 virus. This is crucial to speed up clinical diagnosis, predict prognostic outcomes and target treatment. Funding: We acknowledge funding to AAF by a UKRI Turing AI Fellowship and to CEC by a personal NIHR Career Development Fellowship (grant number NIHR-2016-090-015). JKQ has received grants from The Health Foundation, MRC, GSK, Bayer, BI, Asthma UK-British Lung Foundation, IQVIA, Chiesi AZ, and Insmed. This work is supported by BREATHE - The Health Data Research Hub for Respiratory Health [MC_PC_19004]. BREATHE is funded through the UK Research and Innovation Industrial Strategy Challenge Fund and delivered through Health Data Research UK. Imperial College London is grateful for the support from the Northwest London NIHR Applied Research Collaboration. The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

20.
Cureus ; 14(2): e21903, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35265426

RESUMO

Burns can be devastating and result in unwanted consequences with prolonged length of hospital stay. The mortality rate increases as the total body surface area increases, so proper management of patients with extensive degrees of burns is crucial for their survival. We present the hospital course, management, and survival of a patient after he sustained a 95% total body surface area, second-degree burn from a gas flame. Furthermore, we present from the literature different cases of patients with large total body surface area burns and survived after being managed in burns specialty centers. Although large total body surface area burns can result in significant morbidity and mortality, early management and intervention by an expert surgical team can result in positive outcomes.

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