Patient Preferences for the Management of Gastrointestinal Symptoms in Kidney Transplantation: a Discrete Choice Experiment.

Introduction: Gastrointestinal (GI) symptoms in kidney transplant are common and debilitating. We aimed to ascertain patients' preferences for GI symptom management options to help future interventions align with treatment priorities. Methods: A discrete choice experiment was conducted with kidney transplant recipients in 3 Australian nephrology units. A multinomial logit model was used to quantify the preferences and trade-offs between 5 characteristics: cost, formulation, symptom burden, dietary changes, and medication quantities. Results: Seventy patients participated (mean age ± SD: 47 ± 15 years, 56% female), 57% had GI symptoms. Patients preferred interventions that will achieve complete resolution of GI symptoms compared to no improvement (odds ratio [95% confidence interval]: 15.3 [1.80, 129.50]), were delivered as a tablet rather than a sachet (1.6 [1.27, 2.08]), retained their current diet compared to eliminating food groups (6.0 [2.19, 16.27]), reduced medication burden (1.4 [1.06, 1.79]), and had lower costs (0.98 [0.96, 1.00]). Participants would be willing to pay AUD$142.20 [$83.90, $200.40] monthly to achieve complete resolution of GI symptoms or AUD$100.90 [$9.60, $192.10] to have moderate improvement in symptoms. Conclusions: Interventions that are highly effective in relieving all GI symptoms without the need for substantive dietary changes, and in tablet form, are most preferred by kidney transplant recipients.

The CKD bowel health study: understanding the bowel health and gastrointestinal symptom management in patients with chronic kidney disease: a mixed-methods observational longitudinal study (protocol).

BACKGROUND: Gastro-intestinal (GI) intolerance is a frequently reported outcome in patients with kidney failure receiving maintenance dialysis and those who have received kidney transplants. Symptoms of GI intolerance (diarrhoea, constipation, bloating, abdominal pain, heart burn, and reflux) are associated with significant reduction in quality of life, morbidity, and increased used of healthcare resources. Having chronic kidney disease (CKD), together with related changes in diet and medication, may alter the gut microbiota and the microbial-derived uraemic metabolites that accumulate in kidney failure, and contribute to various complications including chronic diarrhoea, opportunistic infections, and drug-related colitis. Despite the high disease burden among patients with kidney replacement therapies, GI symptoms are often under-recognised and, consequently limited resources and strategies are devoted to the management of gastrointestinal complications in patients with CKD. METHODS: The CKD Bowel Health Study is a multi-centre mixed-methods observational longitudinal study to better understand the bowel health and GI symptom management in patients with CKD. The program comprises of a longitudinal study that will assess the burden and risk factors of GI intolerance in patients treated with maintenance dialysis; a semi-structured interview study that will describe experiences of GI intolerance (including symptoms, treatment, self-management) in transplant candidates and recipients; and a discrete choice experience to elicit patient preferences regarding their experiences and perspectives of various intervention strategies for the management of GI symptoms after kidney transplantation. DISCUSSION: This proposed program of work aims to define the burden the GI intolerance in patients with kidney failure and generate evidence on the patients' experiences of GI intolerance and their perspectives on their clinical and own management strategies of these symptoms, ensuring a patient-centred approach to guide clinical decision making and to inform the best study design for intervention trials. TRIAL REGISTRATION: This study is registered on the Australian New Zealand Clinical Trials Registry (ANZCTR): ACTRN12621000548831 . This study has been approved by the Western Sydney Local Health District Human Research Ethics Committee of New South Wales Health (HREC ETH03007). This study is supported by a National Health and Medical Research Council (NHMRC) Australia Investigator Grant (APP1195414), and an NHMRC Australia Postgraduate Scholarship (APP2005244).

The "Self" under COVID-19: Social role disruptions, self-authenticity and present-focused coping.

Social role disruption is a state involving upheaval of social identities, routines and responsibilities. Such disruption is presently occurring at a global scale due to the COVID-19 pandemic, which poses a threat not only to health and security but also to the social roles that underlie people's daily lives. Our collective response to combat the virus entails, for example, parents homeschooling children, friends socializing online, and employees working from home. While these collective efforts serve the greater good, people's social roles now lack continuity from what was authentic to the roles before the pandemic began. This, we argue, takes a psychological toll. Individuals feel inauthentic, or alienated and out-of-touch from their "true" selves, to the extent their social roles undergo change. As evidence, we report survey (Studies 1 & 4) and experimental (Studies 2 & 3) evidence that COVID-19-related role changes indeed increase inauthenticity. This effect occurs independent of (a) how positively/negatively people feel about COVID-19 (Study 2) and (b) how positively/negatively people feel about the role change itself (Studies 3 & 4). Moreover, we identify two moderators of this effect. First, this effect occurs when (and ostensibly because) the social roles undergoing change are central to an individual's sense of self (Study 2). Second, this effect depends on an individual's temporal perspective. People can safeguard their self-authenticity in the face of changing social roles if they stay focused on the here-and-now (the present and immediate future), rather than focusing on the past (pre-COVID-19) or future (post-COVID-19) (Studies 3 & 4). This advantage for present-focused coping is observed in both the U.S.A. (Study 3) and Hong Kong (Study 4). We suggest that the reason people feel more authentically themselves when they maintain a present focus is because doing so makes the discontinuity of their social roles less salient.

The schema-driven chameleon: how mimicry affects executive and self-regulatory resources.

The authors propose that behavioral mimicry is guided by schemas that enable efficient social coordination. If mimicry is schema driven, then the operation of these schemas should be disrupted if partners behave in counternormative ways, such as mimicking people they generally would not or vice versa, rendering social interaction inefficient and demanding more executive and self-regulatory resources. To test this hypothesis, Experiments 1-3 used a resource-depletion paradigm in which participants performed a resource-demanding task after interacting with a confederate who mimicked them or did not mimic them. Experiment 1 demonstrated impaired task performance among participants who were not mimicked by a peer. Experiments 2 and 3 replicated this effect and also demonstrated a significant reversal in social contexts where mimicry is counternormative, suggesting that inefficiency emerges from schema inconsistency, not from the absence of mimicry per se. Experiment 4 used a divided attention paradigm and found that resources are taxed throughout schema-inconsistent interactions. These findings suggest that much-needed resources are preserved when the amount of mimicry displayed by interacting individuals adheres to norms, whereas resources are depleted when mimicry norms are violated.

High-maintenance interaction: inefficient social coordination impairs self-regulation.

Tasks requiring interpersonal coordination permeate all spheres of life. Although social coordination is sometimes efficient and effortless (low maintenance), at other times it is inefficient and effortful (high maintenance). Across 5 studies, participants experienced either a high- or a low-maintenance interaction with a confederate before engaging in an individual-level task requiring self-regulation. Self-regulation was operationalized with measures of (a) preferences for a challenging task with high reward potential over an easy task with low reward potential (Study 1) and (b) task performance (anagram performance in Study 1, Graduate Record Exam performance in Studies 2 and 3, physical stamina in Study 4, and fine motor control in Study 5). Results uniformly supported the hypothesis that experiencing high-maintenance interaction impairs one's self-regulatory success on subsequent, unrelated tasks. These effects were not mediated through participants' conscious processes and emerged even with a nonconscious manipulation of high-maintenance interaction.

Intron 4 mutation in APC gene results in splice defect and attenuated FAP phenotype.

The adenomatous polyposis coli (APC) protein is a tumor suppressor frequently involved in the development of inherited and sporadic colon cancers. Somatic mutations of the APC gene are found in 80% of all colon cancers. Inherited mutations result in familial adenomatous polyposis (FAP) as well as an attenuated form of this syndrome. FAP is characterized by the early age onset of hundreds to thousands of colonic adenomatous polyps and a virtual certainty of colon cancer unless the colon is removed. The attenuated form of FAP (AFAP) is characterized by fewer adenomas, later onset of adenomas and cancer, and a decreased lifetime cancer risk. We report a 37-year-old man with a history of more than 50 colonic adenomatous polyps, located predominately in the right colon. An insertion of a single thymidine between the second and third base pairs of intron 4 of the APC gene was identified (c.531+2_531+3insT). Monoallelic hybrid cells harboring a single copy of human chromosome 5 were generated from patient lymphoblasts. Sequencing of the APC cDNA product from these cells revealed a single RNA transcript with aberrant splicing in the mutant mRNA whereby exon 4 is deleted. The translational reading frame is shifted after codon 140 and a translational stop is generated predicting a truncated protein of 147 amino acids, thus indicating that the intronic mutation is disease causing. The lack of a secondary transcript from the mutant allele suggests that incomplete exon skipping is not the molecular mechanism behind the attenuated phenotype.