Prioritizing Patient Reported Outcome Measures (PROMs) to use in the clinical care of youth living with mental health concerns: a nominal group technique study.

BACKGROUND: In the past few decades, particularly in the mental health setting, there has been growing interest in using Patient Reported Outcome Measures (PROMs) to assess the efficacy of the treatments in healthcare systems. Despite recent initiatives for global harmonization, there remains a lack of consensus on which PROMs are best practice and appropriate. Engagement of the service users, such as patients and family members/caregivers, is vital at this stage to ensure the selected PROMs are feasible, relevant, and acceptable to them. This study aimed to prioritize PROMs by youth and family/caregiver based on feasibility, relevance, and overall importance to be used in the clinical care of youth living with anxiety and/or depression. METHODS: Ten validated and widely used PROMs were presented to the patients and family/caregivers. Nominal group techniques were employed to prioritize the PROMs based on feasibility, relevance, and overall importance. RESULTS: For patients and families/caregivers, the PROMs, Revised Child Anxiety and Depression Scale (RCAD 25), and The Young Person's Core (YP-CORE) were the highest priorities. Both felt that RCAD 25 was comprehensive, short, easy, and quick to complete, whereas regarding YP-CORE, patients and family/caregivers thought it was also short and relevant. Due to some specific concerns, the Strength and Difficulties Questionnaire and Child Health Questionnaire were the lowest prioritized by patients and family/caregivers. CONCLUSION: It is of utmost importance that patient's and family/caregivers' voices or opinions are considered while selecting and implementing PROMs in mental health settings. Our study provides practical recommendations around measures best suited to achieve this.

Diclofenac prodrugs nanoparticles: An alternative and efficient treatment for rheumatoid arthritis?

We have synthesized new lipidic prodrugs of diclofenac by grafting aliphatic chains (C10, C12, C16 and C18) to diclofenac through an ester bond. Their molecular formulas were confirmed through HR-MS and the formation of ester bond by FTIR and NMR spectroscopy. Nanoparticles of the different prodrugs were successfully formulated using emulsion evaporation method and DSPE-PEG2000 as the only excipient. All nanoparticles were spherical and had a size between 110 and 150 nm, PdI ≤ 0.2 and negative Zeta potential values from -30 to -50 mV. In addition, they were stable upon storage at 4 °C up to 30-35 days. The encapsulation efficiency of the prodrug was above 90 % independently of the aliphatic chain length grafted. Nanoparticles did not induce any toxicity on LPS-activated THP-1 cells up to a concentration of 100 µg/mL (equivalent diclofenac) whereas diclofenac sodium salt IC50 was around 20 µg/mL. Following incubation of nanoparticles with LPS-activated THP-1 cells, a dose dependent inhibition of TNF-α was observed comparable to standard diclofenac sodium. Based on in vitro studies representative nanoparticles, Prodrug 3 NPs (C16 aliphatic chain) were selected for further in vitro and in vivo studies. Upon incubation in murine plasma, Prodrug 3 NPs underwent an enzymatic cleavage and almost 70 % of diclofenac was released from nanoparticles in 8 h. In vivo studies on a collagen induced arthritis murine model showed contrasted results: on one hand Prodrug 3 NPs led to a significant decrease of arthritis score and of paw volume compared to PBS after the second injection, on the other hand the third injection induced an important hepatic toxicity with the death of half of the mice from the NP group. To promote the reduction of inflammation while avoiding hepatic toxicity using NPs would require to precisely study the No Observable Adverse Effect Level and the schedule of administration in the future.

Honey proteins regulate oxidative stress, inflammation and ameliorates hyperglycemia in streptozotocin induced diabetic rats.

BACKGROUND: Diabetes Mellitus (DM) poses a serious health problem worldwide and several inflammatory mediators are involved in the pathogenesis of this disease. Honey composed of various constituents which have been proven to have immunomodulatory and anti-inflammatory properties. The aim of this study is to investigate the in vitro and in vivo effects of Ziziphus honey and its isolated crude proteins in modulation of immune system and inflammation involved in the pathogenesis of diabetes. METHODOLOGY: The proteins from Ziziphus honey were isolated by ammonium sulfate precipitation and estimated by Bradford method. In vitro anti-inflammatory activities were evaluated by inhibition of reactive oxygen species (ROS) from phagocytes via chemiluminescence immunoassay and nitric oxide (NO) by Griess method. Cytotoxicity was evaluated by MTT Assay. The comparative effect of oral and IP routes of honey and isolated proteins was observed in streptozotocin (STZ) induced diabetic male Wistar rats. qRT-PCR technique was utilized for gene expression studies. RESULTS: The honey proteins suppressed phagocyte oxidative burst and nitric oxide (NO) at significantly lower concentrations as compared to crude honey. The isolated proteins showed promising anti-inflammatory and hypoglycemic effects along with maintenance of body weight of rodents via both oral and IP routes, with significant down-regulation of inflammatory markers TNF-α, IL-1ß, IFN-γ, iNOS, caspase 1, Calgranulin A (S100A8) and NF-κB expression in diabetic rats. CONCLUSION: The isolated honey proteins showed better immunomodulatory and therapeutic potential at significantly lower doses as compared to crude honey.

Tailoring care for frail and lonely older people with HIV in Canada: a cross-sectional study.

BACKGROUND: 40-60% of people with HIV report experiencing loneliness, and 5-29% of PWH are frail (depending on the definition used). The risk of death in individuals who are frail and lonely, or frail and socially isolated has recently been estimated to be 1·8 times that in individuals who are not frail, lonely, or socially isolated. The aim of the present study was to determine the prevalence of loneliness, and other vulnerabilities related to ageing, in frail older adults with HIV. METHODS: We assessed frailty with the Clinical Frailty Scale (CFS) in a cross-sectional, convenience sample of people with HIV aged 50 years or older in Southern Alberta, Canada. All Southern Alberta Clinic patients aged 50 years or older who attended a virtual or in-person clinic visit between March and October, 2020, and who underwent frailty screening were included in the present analyses. Individuals scoring 4 or higher on the CFS then completed a structured questionnaire to provide information on additional co-factors, including loneliness (Three-item Loneliness Scale), falls, impaired gait and balance, polypharmacy, unintentional weight loss, food insecurity, and subjective cognitive concerns. Age, sex, nadir CD4 cell count, duration of known HIV infection, ethnicity, and risk category were evaluated for associations with frailty. We used t tests to compare means and Pearson χ2 tests to compare proportions. Patients gave written informed consent for use of data. The use of data was approved by the University of Calgary Conjoint Heath Research Ethics Board. FINDINGS: We assessed frailty in 292 older people with HIV. The mean age was 59 years (range 50-86 years) and 45 (16%) were women. On the basis of a score of 4 or greater on the CFS, 40 (14%) participants were identified as frail. Frail individuals tended to be older than those who were not frail (mean age 61·9 years, SD 8·5 versus 58·4 years, SD 6·3; t test difference 3·5, 95% CI 1·3-5·7; p=0·0011). However, there was no association between frailty status and sex, nadir CD4 cell count, duration of known HIV infection, or self-reported ethnicity. Frail individuals were more likely to report injection drug use as a component of their risk for acquisition than were non-frail individuals. Of the frail participants, 15 (42%) reported loneliness, 15 (42%) had fallen in the past year, and 18 (50%) reported impaired gait or balance. One-fifth (8) reported unintentional weight loss and 12 (33%) experienced food insecurity. Nearly 40% (14) reported subjective memory concerns. INTERPRETATION: In this sample of ageing people with HIV, frailty and loneliness were prevalent. Given the increased risk of death when frailty and loneliness are both present, upstream and targeted interventions are urgently needed. These might include measures to address loneliness, risk of falls, weight loss, food insecurity, and memory concerns. FUNDING: Canadian Foundation for Healthcare Improvement, Advancing Frailty Care in the Community.

Therapeutic appraisal of ephedrine against rheumatoid arthritis: A new indication.

Ephedra, natural flora has been used traditionally to treat rheumatism since decades. The scientific evidence of anti-rheumatic effect of this plant has also been reported. But the anti-rheumatic activity of major constituent of this plant (ephedrine) has not been evaluated. Based on this, the current study was aimed to assess anti-arthritic activity of ephedrine by using in vitro and in vivo approaches. Correspondingly, enzyme linked immunosorbent assay was performed for the estimation of prostaglandins E2 (PGE2) and tumor necrosis factor-α (TNF-α) in serum of formaldehyde-induced arthritic animals. The results elaborated significant reduction in albumin denaturation and remarkable progress on stabilization of red blood cells outer membrane at higher concentration during in vitro experiments. The ephedrine (40mg/kg) revealed noteworthy (p<0.001) inhibition in paw swelling in animals intoxicated with albumin as well as formaldehyde as compared to animals of control group by in vivo results. In this assay, ephedrine (20 & 40 mg/kg orally) significantly suppressed the level of these inflammatory markers (PGE2 & TNF-α). Ephedrine exhibited anti-arthritic effect by decreasing pro-inflammatory cytokines (PGE2 & TNF-α). This experimental work pharmacologically supports the use of ephedrine as anti-rheumatic drug but limited to evaluate in immunological arthritic model.

Pharmacological support to anti-arthritic prospective of physostigmine: a new approach.

Rheumatoid arthritis (RA) is a slowly progressing inflammatory autoimmune disease. Several features are involved in the RA pathogenesis in addition to environmental and genetic factors. Previously it has been reported that acetyl cholinesterase (AChE) activity is enhanced in old age and may contribute in the progression of RA. The current experimental work was projected to assess the activity of physostigmine (a cholinesterase inhibitor) for treatment of RA. In vitro and in vivo approaches were used for such evaluation. However, enzyme linked immunosorbent assays (ELISA) was performed to determine the concentrations of Prostaglandins E2 (PGE2) and tumor necrosis factor-α in arthritic rats after treatment with physostigmine. Moreover, anti-oxidant assays were employed to calculate the level of super oxide dismutase (SOD) and catalase peroxidase (CAT) in tissue of treated animals. The results claimed the dose dependent protective and stabilizing effect of physostigmine on denaturation of albumin (egg and bovine serum) protein and human red blood cell membrane, respectively, through in vitro studies. Furthermore, the physostigmine (10 and 20 mg/kg) significantly (p < 0.001) reduced the swelling of paw after induction of arthritis with formaldehyde or complete Freund's adjuvant (CFA) as compared to arthritic control animals. Moreover, significant (p < 0.001) reduction in the levels of inflammatory markers (PGE2 and TNF-α) at doses of 10 and 20 mg/kg of physostigmine has been observed in ELISA test. Likewise, there was a prominent rise in levels of SOD and CAT in animals treated with physostigmine. These findings pharmacologically conclude the anti-arthritic effect of physostigmine.

Eliciting Patient Experiences About Their Care After Cardiac Surgery.

BACKGROUND: Experience surveys provide an opportunity for patients to give their feedback about health care processes and services. Unfortunately, the most current surveys have been designed as "one-size fits-all" tools, and thus, do not take into account items pertaining to specific clinical groups. The objective of this study was to gain a deeper understanding of the specific aspects of care deemed important to cardiac surgery patients. METHODS: Individual semistructured telephone interviews were conducted with a cohort of patients who had previously underwent cardiac surgery. Interviews were recorded and transcribed. Using a phenomenological approach, a thematic analysis was used to generate a list of themes and subthemes deemed important by participants. RESULTS: Eight interviews were conducted in July and August 2019. Participants included 7 men and 1 woman, ranging from 55 to 84 years of age. Five key themes emerged from the data: (1) overall experience; (2) communication; (3) the physical hospital environment; (4) care needs and ongoing management; and (5) person-centred care. Our interviews revealed that participants had many overwhelmingly positive experiences with care. Through reports of their own experiences, participants highlighted important areas that might be improved. CONCLUSIONS: Our results confirm and expand upon those highlighted in quantitative research by our group. Findings and knowledge derived from this study might be used to inform quality improvement activities. These might also play a key role in the development of a patient experience survey, specifically for those who undergo cardiac surgery; thus addressing a potential limitation of surveys currently in use.

CONTEXTE: Les sondages sur l'expérience offrent l'occasion aux patients de transmettre leur point de vue au sujet des services et des processus de soins de santé. Malheureusement, la plupart des sondages actuels sont conçus comme des outils universels, et ne prenent donc pas en considération certains aspects propres à des groupes cliniques précis. L'objectif de cette étude est de mieux cerner les aspects précis des soins qui sont jugés importants par les patients qui ont subi une intervention chirurgicale cardiaque. MÉTHODOLOGIE: Des entretiens téléphoniques individuels semi-structurés ont été menés avec une cohorte de patients ayant subi une intervention chirurgicale cardiaque. Les entretiens ont été enregistrés et retranscrits. Une analyse thématique utilisant une approche phénoménologique a été effectuée pour générer une liste de thèmes et de sous-thèmes jugés importants par les participants. RÉSULTATS: Huit entretiens ont été réalisés en juillet et en août 2019. Les participants regroupaient sept hommes et une femme, âgés de 55 à 84 ans. Les données recueillies ont permis de cerner cinq thèmes clés : 1) expérience globale; 2) communication; 3) environnement physique à l'hôpital; 4) besoins en matière de soins et prise en charge continue; et 5) soins axés sur le patient. Nos entretiens ont révélé que les participants avaient eu plusieurs expériences de soins extrêmement positives. En relatant leurs propres expériences, les participants ont souligné d'importants aspects qui pourraient être améliorés. CONCLUSIONS: Nos résultats confirment ceux des recherches quantitatives effectuées par notre groupe, et viennent les étayer. Les données et les résultats générés par cette étude pourraient être utilisés pour mettre au point des mesures visant l'amélioration de la qualité. Ils pourraient également jouer un rôle important dans la création d'un sondage sur l'expérience des patients, et plus précisément l'expérience des patients ayant subi une intervention chirurgicale cardiaque, et ainsi remédier aux limites possibles des sondages utilisés à l'heure actuelle.

ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives.

BACKGROUND: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. METHODS: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. RESULTS: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 µM), 24 (IC50 = 41.8 ± 1.5 µM), 26 (IC50 = 10.6 ± 2.8 µM), 28 (IC50 = 20.9 ± 1.5 µM), and 41 (IC50 = 4.6 ± 0.3 µM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 µM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 µM), 14 (IC50 = 216.5 ± 6.2 µM), 16 (IC50 = 187.4 ± 2.2 µM), and 20 (IC50 = 196.2 ± 2.0 µM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring "R" played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 µM). CONCLUSION: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.