The effectiveness of patient activation interventions in adults with chronic kidney disease: A systematic review and meta-analysis.

BACKGROUND: Chronic kidney disease (CKD) is a complex health condition that profoundly impacts an individual's general health and well-being throughout their entire lifetime. People with CKD require the knowledge, confidence, and skills to actively self-manage their health. This is referred to as patient activation. The efficacy of interventions to increase patient activation in the CKD population is unclear. AIM: This study aimed to examine the effectiveness of patient activation interventions on behavioral health-related outcomes among people with CKD stages 3-5. METHODS: A systematic review and meta-analysis of randomized controlled trials (RCTs) of patients with CKD stages 3-5 was performed. MEDLINE, EMCARE, EMBASE, and PsychINFO databases were searched between 2005 and February 2021. Risk of bias was assessed using the Joanna Bridge Institute critical appraisal tool. RESULTS: Nineteen RCTs that enrolled 4414 participants were included for synthesis. Only one RCT reported patient activation using the validated 13-item patient activation measure (PAM-13). Four studies demonstrated strong evidence that the intervention group developed a higher level of self-management compared to the control group (standardized mean differences [SMD] = 1.12, 95% CI [0.36, 1.87], p = .004). Eight RCTs led to a significant improvement in self-efficacy (SMD = 0.73, 95% CI [0.39, 1.06], p < .0001). There was weak to no evidence on the effect of the strategies shown on the physical component and mental components of health-related quality of life, and medication adherence. LINKING EVIDENCE TO ACTION: This meta-analysis highlights the importance of including tailored interventions using a cluster approach including patient education, goal setting with individualized action plan, and problem-solving to engage patients to be more actively involved in the self-management of their CKD.

Gastrointestinal symptoms in patients receiving dialysis: A systematic review.

AIM: The aim of the present study was to describe the prevalence of all gastrointestinal (GI) symptoms reported by dialysis patients, as well as the tools being used for diagnosis. GI symptoms are commonly reported in patients having haemodialysis (HD) and peritoneal dialysis (PD), but there are multiple definitions and assessment tools reported in the literature. METHODS: A comprehensive systematic review was undertaken using five databases (Embase, Medline, CINAHL, Psycinfo and Web of Science) between 1996 and 2017. Articles were critically appraised using the Newcastle Ottawa Scale (NOS). Data collected were analyzed in a Microsoft Excel spreadsheet. RESULTS: Thirty studies (24 cross-sectional, six cohort) met the inclusion criteria. In total 5161 patients were studied (3804 HD and 1507 PD). Fifteen studies included HD, five included PD and 10 included both dialysis modalities. GI symptoms were heterogeneous, with the reported prevalence highly dependent on the definitions used, inclusion/exclusion criteria, assessment tools and methods used. The most prevalent symptoms were constipation, indigestion, abdominal pain and reflux. Medication use and dietary data were poorly reported. The most common tools used were Gastrointestinal Symptom Rating Scale (GSRS), Rome II and Rome III. Constipation was more common in HD patients than PD patients. Indigestion, abdominal pain and reflux were commonly reported in both dialysis modalities. CONCLUSIONS: Gastrointestinal symptoms are highly prevalent in people on dialysis; however, the evidence base is limited and further investigation of preventable causes and potential interventions such as medications and diet are required in future research.

Effects of Dietary Fibre from the Traditional Indonesian Food, Green Cincau (Premna oblongifolia Merr.) on Preneoplastic Lesions and Short Chain Fatty Acid Production in an Azoxymethane Rat Model of Colon Cancer.

Green cincau (Premna oblongifolia Merr.) is a traditional food of Indonesia and provides a natural source of dietary fibre and antioxidants. This study evaluated the ability of green cincau, and other dietary fibres with or without the addition of anti-oxidant, epigallocatechin-3-gallate (EGCG), to prevent colorectal cancer in a 12 week azoxymethane (AOM) rat model. While all dietary treatments stimulated short chain fatty acid production (SCFA) in the digesta and faeces, no one treatment was able to significantly protect against aberrant crypt formation (ACF), when compared to the control diet. However, feeding green cincau leaves or extracts did not result in an increase in ACF compared to the control diet. Unexpectedly, when the dietary fibre source was pectin, 0.1% EGCG increased proliferative activity and liver lipid peroxidation when compared to the control diet containing cellulose. Examination of faecal microbial communities identified the presence of short chain acid producing bacteria, but a distinct community profile was not observed from any individual diet group. Overall, this research implies that combining dietary fibre with an antioxidant does not automatically equate to a beneficial response. Further work is required to investigate the health-promoting properties of green cincau.

Manipulation of the gut microbiota using resistant starch is associated with protection against colitis-associated colorectal cancer in rats.

This study evaluated whether dietary resistant starch (RS) and green tea extract (GTE), which have anti-inflammatory and anticancer properties, protect against colitis-associated colorectal cancer (CAC) using a rat model, also investigated potential mechanisms of action of these agents including their effects on the gut microbiota. Rats were fed a control diet or diets containing 10% RS, 0.5% GTE or a combination of the two (RS + GTE). CAC was initiated with 2 weekly azoxymethane (AOM) injections (10mg/kg) followed by 2% dextran sodium sulphate in drinking water for 7 days after 2 weeks on diets. Rats were killed 20 weeks after the first AOM. Colon tissues and tumours were examined for histopathology by H&E, gene/protein expression by PCR and immunohistochemistry and digesta for analyses of fermentation products and microbiota populations. RS and RS + GTE (but not GTE) diets significantly (P< 0.05) decreased tumour multiplicity and adenocarcinoma formation, relative to the control diet. Effects of RS + GTE were not different from RS alone. RS diet caused significant shifts in microbial composition/diversity, with increases in Parabacteroides, Barnesiella, Ruminococcus, Marvinbryantia and Bifidobacterium as primary contributors to the shift. RS-containing diets increased short chain fatty acids (SCFA) and expression of the SCFA receptor GPR43 mRNA, and reduced inflammation (COX-2, NF-kB, TNF-α and IL-1ß mRNA) and cell proliferation P< 0.05. GTE had no effect. This is the first study that demonstrates chemopreventive effects of RS (but not GTE) in a rodent CAC model, suggesting RS might have benefit to patients with ulcerative colitis who are at an increased risk of developing CRC.

Supplementation with Brazil nuts and green tea extract regulates targeted biomarkers related to colorectal cancer risk in humans.

Se and green tea have been shown in epidemiological, observational and preclinical studies to be inversely related to the risk of developing colorectal cancer (CRC). However, there are limited studies to evaluate their regulatory effects on genes/proteins that relate to CRC oncogenesis in human subjects, such as selenoproteins, WNT signalling pathway, inflammation and methylation. This study examined the effects of supplementation of Se using Brazil nuts and green tea extract (GTE) capsules, alone and in combination, on targeted biomarkers. In total, thirty-two volunteers (>50 years of age) with plasma Se≤1·36 µmol/l were randomised to one of three treatment groups: nine to Se (approximately 48 µg/d) as six Brazil nuts, eleven to four GTE capsules (800 mg (-)-epigallocatechin-3-gallate) and twelve to a combination of Brazil nuts and GTE. Blood and rectal biopsies were obtained before and after each intervention. Plasma Se levels, rectal selenoprotein P (SePP) and ß-catenin mRNA increased significantly in subjects consuming Brazil nuts alone or in combination, whereas rectal DNA methyltransferase (DNMT1) and NF-κB mRNA were reduced significantly in subjects consuming GTE alone or in combination. None of the interventions significantly affected rectal acetylated histone H3 or Ki-67 expression at the protein level or plasma C-reactive protein. Effects of the combination of Brazil nuts and GTE did not differ from what would be expected from either agent alone. In conclusion, supplementation of Brazil nuts and/or GTE regulates targeted biomarkers related to CRC oncogenesis, specifically genes associated with selenoproteins (SePP), WNT signalling (ß-catenin), inflammation (NF-κB) and methylation (DNMT1). Their combination does not appear to provide additional effects compared with either agent alone.

Butyrylated starch intake can prevent red meat-induced O6-methyl-2-deoxyguanosine adducts in human rectal tissue: a randomised clinical trial.

Epidemiological studies have identified increased colorectal cancer (CRC) risk with high red meat (HRM) intakes, whereas dietary fibre intake appears to be protective. In the present study, we examined whether a HRM diet increased rectal O(6)-methyl-2-deoxyguanosine (O(6)MeG) adduct levels in healthy human subjects, and whether butyrylated high-amylose maize starch (HAMSB) was protective. A group of twenty-three individuals consumed 300 g/d of cooked red meat without (HRM diet) or with 40 g/d of HAMSB (HRM+HAMSB diet) over 4-week periods separated by a 4-week washout in a randomised cross-over design. Stool and rectal biopsy samples were collected for biochemical, microbial and immunohistochemical analyses at baseline and at the end of each 4-week intervention period. The HRM diet increased rectal O(6)MeG adducts relative to its baseline by 21% (P < 0.01), whereas the addition of HAMSB to the HRM diet prevented this increase. Epithelial proliferation increased with both the HRM (P < 0.001) and HRM + HAMSB (P < 0.05) diets when compared with their respective baseline levels, but was lower following the HRM + HAMSB diet compared with the HRM diet (P < 0.05). Relative to its baseline, the HRM + HAMSB diet increased the excretion of SCFA by over 20% (P < 0.05) and increased the absolute abundances of the Clostridium coccoides group (P < 0.05), the Clostridium leptum group (P < 0.05), Lactobacillus spp. (P < 0.01), Parabacteroides distasonis (P < 0.001) and Ruminococcus bromii (P < 0.05), but lowered Ruminococcus torques (P < 0.05) and the proportions of Ruminococcus gnavus, Ruminococcus torques and Escherichia coli (P < 0.01). HRM consumption could increase the risk of CRC through increased formation of colorectal epithelial O(6)MeG adducts. HAMSB consumption prevented red meat-induced adduct formation, which may be associated with increased stool SCFA levels and/or changes in the microbiota composition.

Housing experimental rats in solid-based cages with digestible bedding may confound outcomes of nutritional studies.

BACKGROUND: Rats used in nutritional studies are often kept in wire-based cages to prevent ingestion of bedding and minimise ingestion of faeces. However, wire-based cages are criticised because of potential negative animal welfare implications. This study investigated the effects of wire and solid-based cages with corncob bedding on large bowel fermentation and microbiota. Rats were group housed in wire or solid-based cages and fed either a low-fibre (LF) diet or a high-fibre (HF) diet composed of resistant starch for 4 weeks. RESULTS: Bedding material was observed in faeces of rats housed in solid-based cages. Caging type and diet altered large bowel fermentation variables and bacterial populations. Caecal digesta weight was lower in rats fed HF diet and maintained on bedding than in HF-fed rats maintained on wire. Bacteria abundance associated with fibre fermentation was higher in LF-diet fed rats maintained on bedding compared with LF-fed rats housed on wire. CONCLUSION: Maintaining rats in solid-based cages with corncob bedding alters large bowel fermentation and bacterial communities owing to ingestion of bedding. These changes may confound outcomes of nutritional studies, particularly those investigating the health effects of fibres. The use of wire-based caging may be justified in research of this type.

The futility of post-haemodialysis blood glucose levels: A retrospective cohort study.

BACKGROUND: Frequent blood glucose tests are performed for people with diabetes receiving haemodialysis. OBJECTIVES: To determine the rate of out-of-range post-haemodialysis blood glucose levels that are clinically acted upon, the intervention and outcome of each intervention, and the associations between post-haemodialysis blood glucose levels and relevant clinical predictors. DESIGN: 12-month retrospective cohort medical record review in one Australian haemodialysis centre. Post-haemodialysis blood glucose levels, prehaemodialysis blood glucose levels, time of treatment, diabetes medications, intradialytic fluid removal, dialysate dextrose concentration, clinical actions, interventions, and outcomes on out-of-range blood glucose levels were retrieved. PARTICIPANTS: 22 participants with a median time receiving dialysis 3.1 years (interquartile range 2.3-4.7). MEASUREMENTS AND RESULTS: The proportion of out-of-range post-haemodialysis blood glucose levels was 87.3% (95% confidence interval, 86.1%-88.5%). No out-of-range post-haemodialysis blood glucose levels were clinically acted upon. Out-of-range post-haemodialysis blood glucose levels were 4.6 times more likely if a higher dextrose bath was used (95% confidence interval: 3.3; 6.3. p < 0.001). The odds of the post-haemodialysis blood glucose levels increased by each 1 mmol/L. Intradialytic fluid removal, dialysate dextrose concentration, sex, dialysis time, anti-hyperglycaemic agents were also associated with out-of-range post-haemodialysis blood glucose levels. CONCLUSION: Routine post-haemodialysis blood glucose levels testing has limited clinical utility in care for people with diabetes receiving maintenance haemodialysis. Higher dextrose dialysate may require individual titration depending on prehaemodialysis blood glucose levels.

Patient activation in advanced chronic kidney disease: a cross-sectional study.

BACKGROUND: Patient activation refers to the knowledge, confidence and skills required for the management of chronic disease and is antecedent to self-management. Greater self-management in chronic kidney disease (CKD) results in improved patient experience and patient outcomes. AIM: To examine patient activation levels in people with CKD stage 5 pre-dialysis and determine associations with sociodemographic characteristics, treatment adherence and healthcare utilisation. METHODS/DESIGN: People with CKD stage 5 not receiving dialysis from one Australian kidney care service. Patient activation was measured using the 13-item Patient Activation Measure (PAM-13). Sociodemographic and clinical outcome data (emergency department visits, admissions) were collected from medical records. Morisky Medication Adherence Scale was used to determine self-report medication adherence. RESULTS: Two hundred and four participants completed the study. The mean PAM-13 score was 53.4 (SD 13.8), with 73% reporting low activation levels (1 and 2). Patient activation scores significantly decreased with increased age (P < 0.001) and significantly increased with higher educational levels (P < 0.001). Higher patient activation level was associated with fewer hospital emergency department visits (P = 0.03) and increased medication adherence (P < 0.001). CONCLUSION: Patient activation levels are low in people with CKD stage 5 not receiving dialysis suggesting limited ability for self-management and capacity for optimally informed decisions about their healthcare. Efforts to improve patient activation need to consider age and education level.

Ecological Momentary Assessment to Explore Fatigue, Mood, and Physical Activity Levels in People Receiving Peritoneal Dialysis.

Introduction: Fatigue is a frequent and debilitating symptom that contributes to poor quality of life for people receiving peritoneal dialysis. Ecological momentary assessment using mobile technology (mEMA) is a novel survey technique that can collect symptom data in real-time and has not been trialed in a peritoneal dialysis cohort. The study aimed to explore real-time fluctuations and associations between fatigue, mood, and physical activity using mEMA. Methods: Adults receiving peritoneal dialysis completed fatigue and mood scales, via a mobile application (app), 5 times daily for 7 days and, concurrently wore an accelerometer. A feasibility questionnaire was completed on the eighth day. Results: Forty-eight adults completed the study. Within-day fatigue fluctuations were observed with severity lowest during mid-morning to early afternoon and peaking at bedtime. Associations between fatigue and mood were observed with a 1-unit change in mood score conferring a 5.2-unit change in fatigue (P < 0.01). Higher volume of physical activity was associated with lower fatigue and enhanced mood. Overall adherence to the app-based surveys was 73% with most participants reporting mobile phones and the mEMA app being easy to use. Conclusion: People receiving peritoneal dialysis experience within day and day-to-day fluctuations in fatigue that appear highly variable. Higher fatigue severity was associated with poorer mood and lower physical activity levels with future studies required to explore if physical activity-based interventions could be a potential strategy for the management of these symptoms. Furthermore, mEMA, and mobile phones, were feasible to capture symptom data with potential to be employed in future research or, as part of improved care.

Histone deacetylase inhibition in colorectal cancer cells reveals competing roles for members of the oncogenic miR-17-92 cluster.

Diet-derived butyrate, a histone deacetylase inhibitor (HDI), decreases proliferation and increases apoptosis in colorectal cancer (CRC) cells via epigenetic changes in gene expression. Other HDIs such as suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) have similar effects. This study examined the role of microRNAs (miRNAs) in mediating the chemo-protective effects of HDIs, and explored functions of the oncogenic miR-17-92 cluster. The dysregulated miRNA expression observed in HT29 and HCT116 CRC cells could be epigenetically altered by butyrate, SAHA and TSA. These HDIs decreased expression of miR-17-92 cluster miRNAs (P < 0.05), with a corresponding increase in miR-17-92 target genes, including PTEN, BCL2L11, and CDKN1A (P < 0.05). The decrease in miR-17-92 expression may be partly responsible for the anti-proliferative effects of HDIs, with introduction of miR-17-92 cluster miRNA mimics reversing this effect and decreasing levels of PTEN, BCL2L11, and CDKN1A (P < 0.05). The growth effects of HDIs may be mediated by changes in miRNA activity, with down-regulation of the miR-17-92 cluster a plausible mechanism to explain some of the chemo-protective effects of HDIs. Of the miR-17-92 cluster miRNAs, miR-19a and miR-19b were primarily responsible for promoting proliferation, while miR-18a acted in opposition to other cluster members to decrease growth. NEDD9 and CDK19 were identified as novel miR-18a targets and were shown to be pro-proliferative genes, with RNA interference of their transcripts decreasing proliferation in CRC cells. This is the first study to identify competing roles for miR-17-92 cluster members, in the context of HDI-induced changes in CRC cells.

Repair and removal of azoxymethane-induced O6-methylguanine in rat colon by O6-methylguanine DNA methyltransferase and apoptosis.

Azoxymethane (AOM) is an alkylating agent that generates mutagenic and carcinogenic O(6)-methylguanine (O(6)meG) adducts in DNA. O(6)meG has been detected in human colonic DNA; hence, understanding the innate cellular events occurring in response to the formation of O(6)meG is important in developing preventive strategies for colorectal cancer. We explored the time-course, dose-response, and kinetics of O(6)meG formation and its removal by the DNA repair protein, O(6)-methylguanine DNA methyltransferase (MGMT), and apoptosis. In rats given AOM (10 mg/kg), the formation of O(6)meG occurs within 2 h of exposure, accompanied by rapid depletion of MGMT activity and followed by the induction of an acute apoptotic response that peaks at 6-8 h. MGMT repair and apoptosis are dependent on AOM dose and O(6)meG load. Apoptosis is initiated only when a high O(6)meG load is present and MGMT activity is fully depleted. AOM, 10 mg/kg, overwhelms MGMT repair for about 96 h and renewed MGMT activity is only observed once O(6)meG is no longer detectable. A threshold for apoptosis is observed at 6 h after 6 mg/kg AOM, when a high O(6)meG persists and MGMT activity is very low. These data suggest that apoptosis is probably triggered by O(6)meG, but only once the capacity of MGMT to repair O(6)meG is exhausted. In the colonic epithelium, apoptosis may be complementary to MGMT, in terms of minimising potentially mutagenic events and maintaining a healthy genome.

Dietary red meat aggravates dextran sulfate sodium-induced colitis in mice whereas resistant starch attenuates inflammation.

BACKGROUND: Although a genetic component has been identified as a risk factor for developing inflammatory bowel disease, there is evidence that dietary factors also play a role in the development of this disease. AIMS: The aim of this study was to determine the effects of feeding a red meat diet with and without resistant starch (RS) to mice with dextran sulfate sodium (DSS)-induced colitis. METHODS: Colonic experimental colitis was induced in Balb/c mice using DSS. The severity of colitis was evaluated based on a disease activity index (based on bodyweight loss, stool consistency, rectal bleeding, and overall condition of the animal) and a histological score. Estimations were made of numbers of a range of different bacteria in the treatment pools of cecal digesta using quantitative real-time PCR. RESULTS: Consumption of a diet high in red meat increased DSS-induced colitis as evidenced by higher disease activity and histopathological scores. Addition of RS to the red meat diet exerted a beneficial effect in acute DSS-induced colitis. Subjective analysis of numbers of a range of bacterial targets suggest changes in the gut microbiota abundance were induced by red meat and RS treatments and these changes could contribute to the reported outcomes. CONCLUSIONS: A dietary intake of red meat aggravates DSS-induced colitis whereas co-consumption of resistant starch reduces the severity of colitis.

6-bromoisatin found in muricid mollusc extracts inhibits colon cancer cell proliferation and induces apoptosis, preventing early stage tumor formation in a colorectal cancer rodent model.

Muricid molluscs are a natural source of brominated isatin with anticancer activity. The aim of this study was to examine the safety and efficacy of synthetic 6-bromoisatin for reducing the risk of early stage colorectal tumor formation. The purity of 6-bromoisatin was confirmed by 1H NMR spectroscopy, then tested for in vitro and in vivo anticancer activity. A mouse model for colorectal cancer was utilized whereby colonic apoptosis and cell proliferation was measured 6 h after azoxymethane treatment by hematoxylin and immunohistochemical staining. Liver enzymes and other biochemistry parameters were measured in plasma and haematological assessment of the blood was conducted to assess potential toxic side-effects. 6-Bromoisatin inhibited proliferation of HT29 cells at IC50 223 µM (0.05 mg/mL) and induced apoptosis without increasing caspase 3/7 activity. In vivo 6-bromoisatin (0.05 mg/g) was found to significantly enhance the apoptotic index (p≤0.001) and reduced cell proliferation (p≤0.01) in the distal colon. There were no significant effects on mouse body weight, liver enzymes, biochemical factors or blood cells. However, 6-bromoisatin caused a decrease in the plasma level of potassium, suggesting a diuretic effect. In conclusion this study supports 6-bromoisatin in Muricidae extracts as a promising lead for prevention of colorectal cancer.

Nephrology nurses' perspectives working with patients experiencing needle-related distress.

BACKGROUND: A key skill of nephrology nursing is cannulation of patients receiving haemodialysis. Traumatic and unsuccessful cannulation experiences, particularly in the initial weeks of haemodialysis, may contribute to the onset of needle distress for patients. OBJECTIVES: To identify the key knowledge, skills and attitudes of nephrology nurses working with haemodialysis patients and the competencies relevant to nephrology nursing working with patients with needle-related distress. DESIGN: A qualitative study involving semistructured interviews. Interviews were audio-recorded, transcribed and deductive, and inductive thematic analysis applied. PARTICIPANTS: Nephrology nurses (n = 17) were interviewed from a tertiary kidney service in South Australia. Nurses had varying roles and years of experience (range 1-30 years) working with dialysis patients within the service. RESULTS: Two overarching themes, (1) Flexibility in Practice and Care and (2) Responsibility of Nephrology Nursing, were identified as relevant across all knowledge, skills and attitudes of nephrology nurses working with patients with needle-related distress. Thirty-six knowledge, skills and attitudes were identified; 12 related to knowledge, 14 related to skills and 10 were identified as attitudes and were summarised under seven broad competencies. CONCLUSION: This study identifies potential knowledge, skills and attitudes and competencies required for nephrology nurses working with patients with needle-related distress. It highlights strategies that may prevent the onset and worsening of needle-related distress, as well as reduce it. It also brings to light that nurses desire additional education regarding strategies to improve the patient experience of cannulation and nurse confidence and skill in this area.

The impact on patients of the tertiary-primary healthcare interface in kidney failure: a qualitative study.

BACKGROUND: Clinicians and patients have reported fragmentation in the primary and tertiary healthcare interface. However, perspectives of service navigation and the impacts of fragmentation are not well defined, particularly for patients transitioning to dialysis. This study aimed to define patient perspectives of the functioning of the health service interface and impacts on healthcare experiences and engagement, informing patient-centred and outcomes-focused service models. METHODS: A qualitative study was conducted through semi-structured interviews with 25 dialysis patients (16 males) aged 34-78 receiving dialysis across a multi-site tertiary service. Transcripts were analysed thematically. RESULTS: Three main themes were identified: (1) The Changing Nature of General Practitioner (GP) Patient Relationships; (2) Ownership and Leadership in Kidney Care; and (3) The Importance of Nephrologist-GP Communications. Patients perceived an unreliable primary-tertiary service interface which lacked coordinated care and created challenges for primary care continuity. These impacted perceptions of healthcare provider expertise and confidence in healthcare systems. Patients subsequently increased the healthcare sought from tertiary kidney clinicians. The fractured interface led some to coordinate communication between health sectors, to support care quality, but this caused additional stress. CONCLUSIONS: A fragmented primary-tertiary healthcare interface creates challenges for patient service navigation and can negatively impact patient experiences, leading to primary care disengagement, reduced confidence in health care quality and increased stress. Future studies are imperative for assessing initiatives facilitating health system integration, including communication technologies, healthcare provider training, patient empowerment, and specific outcomes in health, economic and patient experience measures, for patients transitioning to dialysis.

Dialysis Needle-Related Distress: Patient Perspectives on Identification, Prevention, and Management.

Introduction: Needle-related distress is common among people receiving hemodialysis and affects quality of life and treatment decisions, yet little evidence exists to guide management. This study explored patients' experiences of needle-related distress to inform the development of prevention, identification, and management strategies. Methods: Semistructured interviews concerning dialysis cannulation, needle-related distress, and potential solutions were conducted with people with current or recent experience of hemodialysis (N = 15) from a tertiary hospital-based service. Interviews ceased at thematic saturation. Transcripts were analyzed thematically. Results: There were 4 themes and 11 subthemes generated: (i) uncovering a hidden source of distress (dismissal and minimization by others; suffering in silence to stay alive; preparation, assessment, and education); (ii) coping with cannulation pain and trauma (interaction between physical damage, pain, and distress; operator dependency-the importance of nurse skill and technique); (iii) the environment created by dialysis nurses (emotional transference; communication during cannulation; valuing empathy and person-centered care; a psychosocially supportive dialysis unit); and (iv) supporting patient self-management of distress (accessing tools to help themselves; distraction to reduce distress). Conclusion: Needle-related distress is an often-hidden element of the hemodialysis experience. Patients learn to tolerate it as an inevitable part of dialysis for survival. Nurses' technical skills and the dialysis environment they create are key determinants of the patient cannulation experience. Proposed solutions include psychological screening, education for patients to self-manage distress, and training for nurses in communication and providing relevant psychological support.

The influence of selenium-enriched milk proteins and selenium yeast on plasma selenium levels and rectal selenoprotein gene expression in human subjects.

Certain forms of dietary Se may have advantages for improving human Se status and regulating the risk for disease, such as cancers, including colorectal cancer (CRC). The present study compared the effects of a Se-enriched milk protein (dairy-Se) with a Se-rich yeast (yeast-Se) on plasma Se levels and rectal selenoprotein gene expression since we reasoned that if these genes were not regulated, there was little potential for regulating the risk for CRC in this organ. A total of twenty-three healthy volunteers with plasma Se in the lower half of the population range were supplemented with dairy-Se (150 µg/d) or yeast-Se (150 µg/d) for 6 weeks, followed by 6 weeks of washout period. Blood was sampled every 2 weeks, and rectal biopsies were obtained before and after Se supplementation and after the washout period. Plasma Se levels and glutathione peroxidase (GPx) activity, and rectal mRNA of selenoprotein P (SeP), cytosolic GPx-1 (GPx-1), gastrointestinal GPx-2 (GPx-2) and thioredoxin reductase-1 (TrxR-1) were measured. Plasma Se levels increased rapidly in both Se groups (P < 0·001); plasma GPx activity was not significantly changed. Rectal SeP mRNA increased at 6 weeks compared with baseline in both Se groups (P < 0·05); only dairy-Se resulted in a sustained elevation of SeP after the washout period (P < 0·05). Rectal GPx-1 and GPx-2 mRNA were higher with dairy-Se (P < 0·05) than with yeast-Se at 6 weeks. In conclusion, three rectal selenoprotein mRNA were differentially regulated by dairy-Se and yeast-Se. Changes in rectal selenoproteins are not predicted by changes in plasma Se; dairy-Se effectively regulates the expression of several rectal selenoproteins of relevance to the risk for CRC.

DNA methylation in the rectal mucosa is associated with crypt proliferation and fecal short-chain fatty acids.

BACKGROUND: DNA methylation varies throughout the normal colorectal mucosa and DNA methylation in normal appearing mucosa is associated with serrated and adenomatous neoplasia elsewhere within the colorectum. AIMS: The purpose of this study was to measure luminal chemistry, rectal proliferation and mucosal DNA methylation and thus determine whether regional and pathological patterns of DNA methylation could be explained by luminal and epithelial factors. METHODS: Twenty healthy subjects had normal rectal mucosal biopsies and a 24-h fecal collection. Rectal biopsies were analyzed for epithelial proliferation (Ki67 immunohistochemistry) and DNA methylation at 17 different markers, including "type A" markers (ESR1, GATA5, HIC1, HPP1, SFRP1), "type C" markers (MGMT, MLH1, CDKN2A, MINT1, MINT2, MINT31, IGF2, CACNA1G, NEUROG1, SOCS1, RUNX3), and LINE-1. Fecal analysis included short-chain fatty acids (SCFA), pH and ammonia. Mean "type A" and CIMP panel methylation Z-scores were calculated. RESULTS: Rectal proliferation was significantly correlated with methylation at ESR1 (ρ = 0.81, P = 0.003) and GATA5 (ρ = 0.78, P = 0.012). LINE-1 methylation was 71.7 vs. 74.1%, in patients with "low" and "high" fecal total SCFA concentration (defined by the median value), respectively (P = 0.0019). On multivariate linear regression "type A" methylation was independently associated with rectal proliferation (P = 0.001). LINE-1 methylation was directly associated with rectal proliferation (P = 0.038) and total fecal SCFA concentration (P = 0.002), and inversely associated with fecal NH(3) concentrations (P = 0.003). CONCLUSIONS: DNA methylation in normal rectal mucosa is associated with crypt proliferation and fecal SCFA concentration. These associations may help to explain regional differences in DNA methylation as well as providing a possible link between the colorectal lumen and carcinogenesis.

Gastrointestinal symptom burden and dietary intake in patients with chronic kidney disease.

BACKGROUND: Gastrointestinal (GI) symptoms can present a significant burden to patients with chronic kidney disease (CKD) but the reported prevalence is inconsistent. OBJECTIVE: To examine the GI burden and dietary intake in patients with CKD with or without dialysis. METHODS: This was a cross-sectional study of 216 adults, recruited from outpatient and dialysis clinics, with CKD stage 4 or 5 not receiving dialysis (CKD-ND), or receiving haemodialysis (HD) or peritoneal dialysis (PD). Three questionnaires were administered: the Bristol Stool Form Scale (BSFS); a modified Gastrointestinal Symptom Rating Scale and a short Food Frequency Questionnaire. Outcomes were stool frequency and consistency, GI symptoms and dietary intake. RESULTS: Data were collected from 216 patients (mean age, 63 years [95% CI: 61, 65]; 63% males; CKD-ND: n = 134; HD: n = 67; PD: n = 15). Mean stool frequency for all groups was one bowel action per day (p = .45) and consistency was normal (BSFS type 4, p = .95). Overall GI symptom burden was low but several symptoms occurred at least "most of the time" including "tiredness/lethargy" (54% of participants), "reduced appetite" (29%), "early satiety" (25%) and "change in taste" (15%). Low intakes of fresh fruit, vegetables, whole-grains and legumes were found. No associations were observed between diet and GI symptoms. CONCLUSION: The overall GI symptom burden was low, but >15% of participants reported several symptoms as occurring most to all of the time. Low intakes of fresh fruit, vegetables, whole-grains and legumes were observed in all CKD patients.