ABSTRACT
BACKGROUND: Individuals with chronic kidney disease experience difficult physical and psychological symptoms, that impact quality of life, and are at increased risk of anxiety and depression. Access to specialist psychological support is limited. This study aimed to support a new service development project, in collaboration with Kidney Care UK, to implement the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, which provides accessible mindfulness techniques and practices to enhance compassion and resilience, and explore its feasibility for people living with stage 4 or 5 kidney disease and transplant. METHODS: A multi-method feasibility design was utilised. Participants over 18 years, from the UK, with stage 4 or 5 kidney disease or post-transplant, and who were not currently undergoing psychotherapy, were recruited to the four-week CMR programme. Data was collected at baseline, post-intervention and three-months post to measure anxiety, depression, self-compassion, mental wellbeing, resilience, and mindfulness. The acceptability of the intervention for a kidney disease population was explored through qualitative interviews with participants, and the Mindfulness Teacher. RESULTS: In total, 75 participants were recruited to the study, with 65 completing the CMR programme. The majority were female (66.2%) and post-transplant (63.1%). Analysis of completed outcome measures at baseline and post-intervention timepoints (n = 61), and three-months post intervention (n = 45) revealed significant improvements in participant's levels of anxiety (p < .001) and depression (p < .001), self-compassion (p = .005), mental wellbeing (p < .001), resilience (p.001), and mindfulness (p < .001). Thematic analysis of interviews with participants (n = 19) and Mindfulness Teacher (n = 1) generated three themes (and nine-subthemes); experiences of the CMR programme that facilitated subjective benefit, participants lived and shared experiences, and practicalities of programme participation. All participants interviewed reported that they found programme participation to be beneficial. CONCLUSION: The findings suggest that the CMR programme has the potential to improve psychological outcomes among people with chronic kidney disease. Future randomized controlled trials are required to further test its effectiveness.
Subject(s)
Mindfulness , Renal Insufficiency, Chronic , Resilience, Psychological , Adult , Female , Humans , Male , Empathy , Feasibility Studies , Mindfulness/methods , Quality of Life , Renal Insufficiency, Chronic/psychology , Renal Insufficiency, Chronic/therapyABSTRACT
BACKGROUND: Kidney disease is a progressive, debilitating condition. Patients experience challenging physical and psychological symptoms and are at increased risk of anxiety, depression, and poor mental wellbeing. Access to specialist psychological or social support is limited, with inadequate provision of psychosocial support available across UK renal units. The COSMIC study (examining the acceptability and feasibility of the Compassionate Mindful Resilience programme for adult patients with chronic kidney disease) aimed to support a new service development project, in partnership with Kidney Care UK, by implementing the Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, and explore its feasibility for patients with stage 4 or 5 kidney disease and kidney transplant recipients. This paper reports on the qualitative exploratory work which examined the experiences of study participants, their adherence to practice, and the acceptability of the intervention. METHOD: Participants (n = 19) took part in semi-structured interviews, which were transcribed, coded, and thematically analysed. RESULTS: Three themes (and nine subthemes) were reported: experiences of the CMR programme that facilitated subjective benefit, participants' lived and shared experiences, and the practicalities of CMR programme participation. All participants reported that they found taking part in the CMR programme to be a beneficial experience. CONCLUSION: The CMR programme was found to be an acceptable intervention for people living with kidney disease and provided tools and techniques that support the mental health and wellbeing of this patient group. Further qualitative exploration into participant experience should be integrated within future trials of this intervention.
ABSTRACT
Kidney disease is often progressive, and patients experience diminished health-related quality of life. In addition, the impact of the coronavirus (COVID-19) pandemic, and its associated restrictions, has brought many additional burdens. It is therefore essential that effective and affordable systems are explored to improve the psychological health of this group that can be delivered safely during the COVID-19 pandemic. The aim of this study is to support a new service development project in partnership with the UK's leading patient support charity Kidney Care UK by implementing the four-session Compassionate Mindful Resilience (CMR) programme, developed by MindfulnessUK, and explore its effectiveness for patients with stage 4 or 5 chronic kidney disease or have received a kidney transplant. The study will utilise a quasi-experimental, pretest/posttest design to measure the effect of the CMR programme on anxiety, depression, self-compassion, the ability to be mindful, wellbeing, and resilience, using pre- and posttests, alongside a qualitative exploration to explore factors influencing the feasibility, acceptability, and suitability of the intervention, with patients (and the Mindfulness Teacher) and their commitment to practice. Outcomes from this study will include an evidence-based mindfulness and compassion programme for use with people with kidney disease, which is likely to have applicability across other chronic diseases.
ABSTRACT
BACKGROUND: Mindfulness can potentially positively impact well-being and resilience in undergraduate nursing students. The psychological well-being of such students undertaking clinical training is paramount to ensure optimal learning, and to equip them with skills to manage their wellbeing in future clinical practice. The aim of our study was to explore the views of undergraduate nursing students in relation to understanding and engaging with mindfulness, and how mindfulness could best be delivered within their university programme. METHODS: An online survey was administered via a cloud-based student response system to a convenience sample of first year undergraduate nursing students completing a Bachelor of Science (BSc) Honours (Hons) degree in nursing at a University in the United Kingdom. Data were analysed using descriptive statistics and thematic analysis. RESULTS: The survey achieved a response rate of 78% (n = 208). Seventy-nine percent of participants had heard of mindfulness and were interested in taking part in a mindfulness programme. Respondents reported that the ideal delivery of the programme would consist of weekly 45-min, in person group sessions, over a 6-week period. Respondents also indicated that a mobile application could potentially facilitate participation in the programme. Thematic analysis of open-ended comments, and free text, within the survey indicated 4 overarching themes: 1) Perceptions of what mindfulness is; 2) Previous mindfulness practice experiences; 3) Impact of mindfulness in nursing; 4) The need for a future well-being initiative for undergraduate nursing students. CONCLUSIONS: Undergraduate nursing students perceived that a mindfulness programme has the potential to enhance well-being and future clinical practice. This student cohort are familiar with mindfulness and want more integrated within their undergraduate curriculum. Further research is required to examine the effectiveness of a tailored mindfulness intervention for this population that incorporates the use of both face-to-face and mobile delivery.
ABSTRACT
A previous report from our laboratory disclosed the identification of PF-04991532 [(S)-6-(3-cyclopentyl-2-(4-trifluoromethyl)-1H-imidazol-1-yl)propanamido)nicotinic acid] as a hepatoselective glucokinase activator for the treatment of type 2 diabetes mellitus. Lack of in vitro metabolic turnover in microsomes and hepatocytes from preclinical species and humans suggested that metabolism would be inconsequential as a clearance mechanism of PF-04991532 in vivo. Qualitative examination of human circulating metabolites using plasma samples from a 14-day multiple ascending dose clinical study, however, revealed a glucuronide (M1) and monohydroxylation products (M2a and M2b/M2c) whose abundances (based on UV integration) were greater than 10% of the total drug-related material. Based on this preliminary observation, mass balance/excretion studies were triggered in animals, which revealed that the majority of circulating radioactivity following the oral administration of [¹4C]PF-04991532 was attributed to an unchanged parent (>70% in rats and dogs). In contrast with the human circulatory metabolite profile, the monohydroxylated metabolites were not detected in circulation in either rats or dogs. Available mass spectral evidence suggested that M2a and M2b/M2c were diastereomers derived from cyclopentyl ring oxidation in PF-04991532. Because cyclopentyl ring hydroxylation on the C-2 and C-3 positions can generate eight possible diastereomers, it was possible that additional diastereomers may have also formed and would need to be resolved from the M2a and M2b/M2c peaks observed in the current chromatography conditions. In conclusion, the human metabolite scouting study in tandem with the animal mass balance study allowed early identification of PF-04991532 oxidative metabolites, which were not predicted by in vitro methods and may require additional scrutiny in the development phase of PF-04991532.
Subject(s)
Enzyme Activators/pharmacokinetics , Glucokinase/metabolism , Hypoglycemic Agents/pharmacokinetics , Imidazoles/pharmacokinetics , Liver/drug effects , Nicotinic Acids/pharmacokinetics , Aged , Animals , Animals, Inbred Strains , Biotransformation , Carbon Radioisotopes , Dogs , Drug Evaluation, Preclinical , Enzyme Activators/analysis , Enzyme Activators/blood , Enzyme Activators/urine , Feces/chemistry , Female , Glucokinase/chemistry , Half-Life , Humans , Hypoglycemic Agents/analysis , Hypoglycemic Agents/blood , Hypoglycemic Agents/urine , Imidazoles/analysis , Imidazoles/blood , Imidazoles/urine , Liver/enzymology , Liver/metabolism , Male , Middle Aged , Molecular Structure , Nicotinic Acids/analysis , Nicotinic Acids/blood , Nicotinic Acids/urine , Organ Specificity , Rats, Sprague-DawleyABSTRACT
Glucokinase (hexokinase IV) continues to be a compelling target for the treatment of type 2 diabetes given the wealth of supporting human genetics data and numerous reports of robust clinical glucose lowering in patients treated with small molecule allosteric activators. Recent work has demonstrated the ability of hepatoselective activators to deliver glucose lowering efficacy with minimal risk of hypoglycemia. While orally administered agents require a considerable degree of passive permeability to promote suitable exposures, there is no such restriction on intravenously delivered drugs. Therefore, minimization of membrane diffusion in the context of an intravenously agent should ensure optimal hepatic targeting and therapeutic index. This work details the identification a hepatoselective GKA exhibiting the aforementioned properties.
Subject(s)
Enzyme Activators/chemistry , Glucokinase/chemistry , Hypoglycemic Agents/chemistry , Allosteric Regulation , Animals , Cells, Cultured , Diabetes Mellitus, Type 2/drug therapy , Drug Evaluation, Preclinical , Enzyme Activators/metabolism , Enzyme Activators/therapeutic use , Glucokinase/metabolism , Hepatocytes/cytology , Hepatocytes/enzymology , Humans , Hypoglycemic Agents/metabolism , Hypoglycemic Agents/therapeutic use , Imidazoles/chemistry , Injections, Intravenous , Niacin/analogs & derivatives , Niacin/chemistry , Rats , Tissue DistributionABSTRACT
In vitro-in vivo correlation (IVIVC) of intrinsic clearance in preclinical species of rat and dog was established using the hepatocyte relay method to support high-confidence prediction of human pharmacokinetics for low-clearance compounds. Good IVIVC of intrinsic clearance was observed for most of the compounds, with predicted values within 2-fold of the observed values. The exceptions involved transporter-mediated uptake clearance or metabolizing enzymes with extensive extrahepatic contribution. This is the first assay available to address low clearance challenges in preclinical species for IVIVC in drug discovery. It extends the utility of the hepatocyte relay method in addressing low clearance issues.
Subject(s)
Hepatocytes/metabolism , Metabolic Clearance Rate/drug effects , Animals , Dogs , Drug Discovery/methods , Drug Evaluation, Preclinical , Male , Membrane Transport Proteins/metabolism , Rats , Rats, WistarABSTRACT
In the Women's Intervention Nutrition Study (WINS), a very low-fat eating pattern decreased breast cancer recurrence. We assessed whether the women's flavonoid intakes varied on the very low fat diet. A total of 550 randomly selected WINS participants who had been treated with conventional therapy (surgery, chemotherapy, and/or radiation) for primary breast cancer were randomized to either a very low fat diet (15% of calories from fat, N = 218) or their usual diets (30% calories from fat, N = 332). We compared their intakes of total flavonoids and 6 flavonoid classes (isoflavones, flavones, flavanones, flavonols, flavan-3-ols, and anthocyanins) for these 2 groups using the U.S. Department of Agriculture food flavonoid database and a flavonoid dietary supplement database on three 24-h dietary recalls at baseline and 12 mo after randomization. At baseline, neither mean fat intakes (31.7% +/- 6.8 SD of calories, n = 332 in the usual diet group and 31.6% +/- 6.8 SD of calories, n = 218 in the very low fat diet group; P = NS) nor flavonoid intakes (218 +/- 283 SD mg/day, n = 332 in the usual diet group and 236 +/- 393 SD mg/day, n = 218 in the very low fat diet group; P = NS) differed. Over half of the women's flavonoid intakes were from the flavan-3-ols. After 12 months of intervention, with 39 participants lost to follow-up, dietary fat intakes were 30.7 +/- 8.4 SD calories (n = 316) among those on their usual diets but were significantly lower among those on the very low fat diet intervention: 21.4 +/- 8.3 SD calories (n = 195), P = <0.05. However, flavonoid intakes remained similar in both groups (201 +/- 252 SD mg/day, n = 316 in the usual diet group vs. 235 +/- 425 SD mg/day, n = 195 in the very low fat group; P = NS). In this random sample of WINS participants, neither total flavonoid intakes nor intakes of subclasses of flavonoids differed between those who had dramatically decreased their fat intakes and those who had not. Flavonoid intakes are therefore unlikely to account for WINS results on differences between the groups in cancer recurrence.