The after-effects of occupational whole-body vibration on human cognitive, visual, and motor function: A systematic review.

Whole-body vibration (WBV) is prevalent in labour-related activities and can have adverse effects on the health and performance of the individuals exposed. However, evidence regarding the extent to which human functionality is affected following occupational WBV exposure has not been collated. The current systematic review sought to synthesize existing literature and assess the strength and direction of evidence regarding the acute after-effects of occupational WBV exposure on cognition, visual function, postural stability, and motor control. We conducted a comprehensive search of AMED, CINAHL, MEDLINE, PubMED, Psychology and Behavioural Sciences Collection, SPORTDiscus, APA PsychInfo, Cochrane Library, EMBASE, HMIC, Global Health, ProQuest Central, Scopus, Web of Science, and the US National Technical Information Service on April 26, 2023. Studies that quantified vibration exposure and measured acute changes in cognition, visual function, postural stability, and motor control from baseline to post-vibration were considered without date restriction. Out of the 2663 studies identified, 32 were eligible for inclusion. Based on the Risk of Bias in Non-Randomized Studies of Exposure (ROBINS-E) tool, the studies demonstrated low (66%), moderate (25%) and high risk of bias (9%). The findings indicate that after exposure to WBV, postural stability either deteriorates or remains unchanged. Inconsistent effects of WBV on cognition were reported, while visual function and motor control showed no pronounced changes following WBV. This might be attributed to assessment limitations such as learning effects in neuropsychological and motor tasks, and non-functional measures of vision employed. There was a lack of consistency in the characterization of vibration exposure and the assessment of associated effects on functional performance. Current evidence is therefore insufficient to provide definitive guidance for updating occupational health and safety regulations regarding WBV. However, this review highlights the potential for WBV to jeopardize post-exposure human performance and, consequently, safety. The completion of the review was supported by a UKRI EPSRC training grant. The review has been registered on PROSPERO (ref CRD42023391075).

Effects of cleft lip on visual scanning and neural processing of infant faces.

Infant faces readily capture adult attention and elicit enhanced neural processing, likely due to their importance evolutionarily in facilitating bonds with caregivers. Facial malformations have been shown to impact early infant-caregiver interactions negatively. However, it remains unclear how such facial malformations may impact early visual processing. The current study used a combination of eye tracking and electroencephalography (EEG) to investigate adults' early visual processing of infant faces with cleft lip/palate as compared to normal infant faces, as well as the impact cleft palate has on perceived cuteness. The results demonstrated a significant decrease in early visual attention to the eye region for infants with cleft palate, while increased visual attention is registered on the mouth region. Increased neural processing of the cleft palate was evident at the N170 and LPP, suggesting differences in configural processing and affective responses to the faces. Infants with cleft palate were also rated significantly less cute than their healthy counterparts (mean difference = .73, p < .001). These results suggest that infants' faces with cleft lip/palate are processed differently at early visual perception. These processing differences may contribute to several important aspects of development (e.g., joint attention) and may play a vital role in the previously observed difficulties in mother-infant interactions.

New role of fat-free mass in cancer risk linked with genetic predisposition.

Cancer risk is associated with the widely debated measure body mass index (BMI). Fat mass and fat-free mass measurements from bioelectrical impedance may further clarify this association. The UK Biobank is a rare resource in which bioelectrical impedance and BMI data was collected on ~ 500,000 individuals. Using this dataset, a comprehensive analysis using regression, principal component and genome-wide genetic association, provided multiple levels of evidence that increasing whole body fat (WBFM) and fat-free mass (WBFFM) are both associated with increased post-menopausal breast cancer risk, and colorectal cancer risk in men. WBFM was inversely associated with prostate cancer. We also identified rs615029[T] and rs1485995[G] as associated in independent analyses with both PMBC (p = 1.56E-17 and 1.78E-11) and WBFFM (p = 2.88E-08 and 8.24E-12), highlighting splice variants of the intriguing long non-coding RNA CUPID1 (LINC01488) as a potential link between PMBC risk and fat-free mass.

The influence of postural threat-induced anxiety on locomotor learning and updating.

The ability to adapt our locomotion in a feedforward (i.e., "predictive") manner is crucial for safe and efficient walking behavior. Equally important is the ability to quickly deadapt and update behavior that is no longer appropriate for the given context. It has been suggested that anxiety induced via postural threat may play a fundamental role in disrupting such deadaptation. We tested this hypothesis, using the "broken escalator" phenomenon: Fifty-six healthy young adults walked onto a stationary walkway ("BEFORE" condition, 5 trials), then onto a moving walkway akin to an airport travelator ("MOVING" condition, 10 trials), and then again onto the stationary walkway ("AFTER" condition, 5 trials). Participants completed all trials while wearing a virtual reality headset, which was used to induce postural threat-related anxiety (raised clifflike drop at the end of the walkway) during different phases of the paradigm. We found that performing the locomotor adaptation phase in a state of increased threat disrupted subsequent deadaptation during AFTER trials: These participants displayed anticipatory muscular activity as if expecting the platform to move and exhibited inappropriate anticipatory forward trunk movement that persisted during multiple AFTER trials. In contrast, postural threat induced during AFTER trials did not affect behavioral or neurophysiological outcomes. These findings highlight that actions learned in the presence of postural threat-induced anxiety are strengthened, leading to difficulties in deadapting these behaviors when no longer appropriate. Given the associations between anxiety and persistent maladaptive gait behaviors (e.g., "overly cautious" gait, functional gait disorders), the findings have implications for the understanding of such conditions.NEW & NOTEWORTHY Safe and efficient locomotion frequently requires movements to be adapted in a feedforward (i.e., "predictive") manner. These adaptations are not always correct, and thus inappropriate behavior must be quickly updated. Here we showed that increased threat disrupts this process. We found that locomotor actions learned in the presence of postural threat-induced anxiety are strengthened, subsequently impairing one's ability to update (or "deadapt") these actions when they are no longer appropriate for the current context.

A comparison of virtual and in person delivery of a full meal replacement program for obesity.

Objective: Full meal replacement (FMR) Intensive Lifestyle Interventions (ILI) have been used for weight management. However, predictors of efficacy with these programs are less clear. The primary objective was to assess weight loss predictors in a community-based FMR ILI program. A secondary objective was to determine if weight loss was different between virtual and in person ILI. Methods: This was a retrospective cohort study involving 234 patients who started the program between 1 January 2016 and 3 March 2021. In the 24-week program, patients spent 12 weeks on FMR and then transitioned back to food for the remainder, with weekly follow up with a physician and group sessions with a dietitian. Visits were in person prior to March 2020 and virtual afterward. Results: Patients' average age was 47.5 years (SD = 12.0) and 73.5% were female. Average weight loss was 14.3% (SD = 6.2%). There was no significant difference in weight loss between virtual and in person programs. Patients on a Glucagon-like Peptide-1 Receptor Agonist prior lost less weight. Other significant associations between groups were baseline Hemoglobin A1C, classes attended, as well as the age since peak weight. Conclusion: Weight loss from virtual ILI was not significantly different from person ILI. More research is needed to determine how to best stratify care as virtual or in person using FMR programs.

Demystifying Dry Powder Inhaler Resistance with Relevance to Optimal Patient Care.

The selection of an inhaler device is a key component of respiratory disease management. However, there is a lack of clarity surrounding inhaler resistance and how it impacts inhaler selection. The most common inhaler types are dry powder inhalers (DPIs) that have internal resistance and pressurised metered dose inhalers (pMDIs) that use propellants to deliver the drug dose to the airways. Inhaler resistance varies across the DPIs available on the market, depending largely on the design geometry of the device but also partially on formulation parameters. Factors influencing inhaler choice include measures such as flow rate or pressure drop as well as inhaler technique and patient preference, both of which can lead to improved adherence and outcomes. For optimal disease outcomes, device selection should be individualised, inhaler technique optimised and patient preference considered. By addressing the common clinically relevant questions, this paper aims to demystify how DPI resistance should guide the selection of the right device for the right patient.

Selection of the right inhaler is important to ensure that patients with respiratory diseases get the most benefit from their treatment. Dry powder inhalers and pressurised metered dose inhalers are the most common inhaler types. Pressurised metered dose inhalers use propellants to deliver the drug to the lungs. In contrast, dry powder inhalers deliver the drug to the lungs by having internal resistance. This restricts the flow of air through the inhaler. As the patient inhales through the inhaler, the resistance against the air flow generates the power to separate the drug molecules and carry them to the lungs. While there are many factors to be considered for inhaler selection, there is often confusion around how resistance should guide selection of inhaler. With low-resistance devices, patients must inhale faster to generate the power to separate the drug molecules, which may be difficult in patients with poor lung function. With high-resistance devices, patients do not need to inhale as fast to separate the drug, and most patients can effectively use the inhaler. This article addresses the common clinically relevant questions to clarify how the internal resistance of the inhaler should be used to help guide the selection of the right device for the right patient.

Rocuronium-Induced Anaphylaxis in the Perioperative Period: A Clinical Review.

Rocuronium, a nondepolarizing neuromuscular blocking agent used for muscle relaxation especially during endotracheal intubation, can cause hypersensitivity reactions. This article provides an overview of anaphylactic reactions; risk factors; and the pathophysiology, presentation, diagnosis, treatment, and nursing implications associated with rocuronium-induced anaphylaxis. Life-threatening anaphylaxis can be immunoglobulin E-mediated or non-immunoglobulin E-mediated and usually occurs after the first dose. Anaphylaxis can present with hypotension and bronchospasm; cutaneal symptoms, such as erythema, may not be obvious. Diagnosis is initially presumptive and may require a transesophageal echocardiogram to rule out other causes of hypotension (eg, pulmonary embolus). Emergency treatment begins with epinephrine administration and fluid boluses; cardiac support devices may be needed. Definitive diagnosis requires early measurement of histamine and tryptase levels and skin testing after the patient recovers from the reaction. Perioperative nurses should be prepared to participate in emergency treatment of anaphylaxis and advocate for testing for a definitive diagnosis.

Titanium Dioxide (E171 Grade) and the Search For Replacement Opacifiers and Colorants: Supplier Readiness Survey, Case Studies and Regulatory Perspective.

Titanium dioxide (TiO2) is used primarily as an opacifier in solid dosage forms and is present in the majority of tablet and capsule dosage forms on the market. The IQ* TiO2 Working Group has previously shown that titanium dioxide has unique properties which are necessary for its function in these formulations and noted that, as the potential replacements lack the semi-conductor properties, high refractive index and whiteness of E171, it might be hard to replicate these properties with alternative materials. In this paper we detail the results of readiness surveys and practical assessments that have been conducted with alternative materials by IQ member companies. A range of technical challenges and regulatory hurdles were identified which mean that, in the short term, it may be difficult to replace titanium dioxide with the currently available alternative materials while readily achieving the same drug product quality attributes, especially for some of the marketed formulations that titanium dioxide is currently used for. We note the higher technical complexity, due to the variability, color fading and identified scale up risk, of E171 free film coatings and the likely impact on development costs and timelines. We also highlight several regulatory hurdles that would have to be overcome if a titanium dioxide replacement was required for some markets but was not mandated by others.

Sigma receptor ligands are potent anti-prion compounds that act independently of sigma receptor binding.

Prion diseases are invariably fatal neurodegenerative diseases of humans and other animals for which there are no treatment options. Previous work from our laboratory identified phenethyl piperidines as novel class of anti-prion compounds. While working to identify the molecular target(s) of these molecules, we unexpectedly discovered ten novel anti-prion compounds based on their known ability to bind to the sigma receptors, σ 1 R and 2 R, which are currently being tested as therapeutic or diagnostic targets for cancer and neuropsychiatric disorders. Surprisingly, however, knockout of the respective genes encoding σ 1 R and σ 2 R ( Sigmar1 and Tmem97 ), in prion infected N2a cells did not alter the anti-prion activity of these compounds, demonstrating that these receptors are not the direct targets responsible the anti-prion effects of their ligands. Further investigation of the most potent molecules established that they are efficacious against multiple prion strains and protect against downstream prion-mediated synaptotoxicity. While the precise details of the mechanism of action of these molecules remains to be determined, the present work forms the basis for further investigations of these compounds in pre-clinical studies. Given the therapeutic utility of several of the tested compounds, including rimcazole and haloperidol for neuropsychiatric conditions, (+)-pentazocine for neuropathic pain, and the ongoing clinical trials of SA 4503 and ANAVEX2-73 for ischemic stroke and Alzheimer's disease, respectively, this work has immediate implications for the treatment of human prion disease.

Using a boundary crossing lens to understand basic science educator and clinical educator collaboration in instructional design.

PURPOSE: Collaborations between basic science educators (BE) and clinical educators (CE) in medical education are common and necessary to create integrated learning materials. However, few studies describe experiences of or processes used by educators engaged in interdisciplinary teamwork. We use the lens of boundary crossing to explore processes described by BE and CE that support the co-creation of integrated learning materials, and the impact that this work has on them. MATERIALS AND METHODS: We conducted qualitative content analysis on program evaluation data from 27 BE and CE who worked on 12 teams as part of a multi-institutional instructional design project. RESULTS: BE and CE productively engaged in collaboration using boundary crossing mechanisms. These included respecting diverse perspectives and expertise and finding efficient processes for completing shared work that allow BE and CE to build on each other's contributions. BE and CE developed confidence in connecting clinical concepts with causal explanations, and willingness to engage in and support such collaborations at their own institutions. CONCLUSIONS: BE and CE report the use of boundary crossing mechanisms that support collaboration in instructional design. Such practices could be harnessed in future collaborations between BE and CE.

Can cognitive training capitalise on near transfer effects? Limited evidence of transfer following online inhibition training in a randomised-controlled trial.

Despite early promise, cognitive training research has failed to deliver consistent real-world benefits and questions have been raised about the experimental rigour of many studies. Several meta-analyses have suggested that there is little to no evidence for transfer of training from computerised tasks to real-world skills. More targeted training approaches that aim to optimise performance on specific tasks have, however, shown more promising effects. In particular, the use of inhibition training for improving shoot/don't-shoot decision-making has returned positive far transfer effects. In the present work, we tested whether an online inhibition training task could generate near and mid-transfer effects in the context of response inhibition tasks. As there has been relatively little testing of retention effects in the literature to date, we also examined whether any benefits would persist over a 1-month interval. In a pre-registered, randomised-controlled trial, participants (n = 73) were allocated to either an inhibition training programme (six training sessions of a visual search task with singleton distractor) or a closely matched active control task (that omitted the distractor element). We assessed near transfer to a Flanker task, and mid-transfer to a computerised shoot/don't-shoot task. There was evidence for a near transfer effect, but no evidence for mid-transfer. There was also no evidence that the magnitude of training improvement was related to transfer task performance. This finding adds to the growing body of literature questioning the effectiveness of cognitive training. Given previous positive findings, however, there may still be value in continuing to explore the extent to which cognitive training can capitalise on near or mid-transfer effects for performance optimisation.

Comparison of Manual versus Automated SARS-CoV-2 Rapid Antigen Testing in Asymptomatic Individuals.

The SARS-CoV-2 pandemic has infected more than 770 M people and killed more than 6.9 M persons worldwide. In the USA, as of August 2023, it has infected more than 103 M people while causing more than 1.1 M deaths. During a pandemic, it is necessary to rapidly identify those individuals infected with the virus so that disease transmission can be stopped. We examined the sensitivity of the Quidel Rapid Antigen test on the manual Sofia 2 platform and the Beckman-Coulter antigen test on the automated DxI-800 system for use in screening asymptomatic individuals at the University of Arizona from March through May 2021. A total of 378 asymptomatic subjects along with 176 validation sets of samples in 23 independent experiments were assessed in side-by-side antigen testing using both assays. Nasal swabs and saliva were used as viral sources. Manual testing (Quidel) was compared with automated testing (Beckman) methods for cost and efficiency. Limit dilution of viral antigen spiked samples was performed to determine sensitivity to antigen load by the tests. The results between the two tests were found to be concordant. Both tests were comparable in terms of detecting low numbers of positive subjects in the asymptomatic population. A concordance of 98% was observed between the two tests. Experiments also demonstrated that saliva specimens were an acceptable viral source and produced comparable results for each test. Overall, the two methods were interchangeable.

The functional role of visual information and fixation stillness in the quiet eye.

The final fixation to a target in far-aiming tasks, known as the quiet eye, has been consistently identified as an important perceptual-cognitive variable for task execution. Yet, despite a number of proposed mechanisms it remains unclear whether the fixation itself is driving performance effects or is simply an emergent property of underpinning cognitions. Across two pre-registered studies, novice golfers (n = 127) completed a series of golf putts in a virtual reality simulation to examine the function of the quiet eye in the absence of visual information. In experiment 1 participants maintained a quiet eye fixation even when all visual information was occluded. Visual occlusion did significantly disrupt motor skill accuracy, but the effect was relatively small (89cm vs 105cm radial error, std. beta = 0.25). In experiment 2, a 'noisy eye' was induced using covertly moving fixation points, which disrupted skill execution (p = .04, BF = 318.07, std. beta = -0.25) even though visual input was equivalent across conditions. Overall, the results showed that performers persist with a long pre-shot fixation even in the absence of visual information, and that the stillness of this fixation confers a functional benefit that is not merely related to improved information extraction.

Investigating how prior knowledge influences perception and action in developmental coordination disorder.

Developmental coordination disorder (DCD) is characterised by a broad spectrum of difficulties in performing motor tasks. It has recently been proposed that a specific deficit in sensorimotor prediction and feedforward planning might underpin these motoric impairments. The purpose of this study was to use a naturalistic object lifting paradigm to examine whether deficits in sensorimotor prediction might underpin the broad spectrum of difficulties individuals with DCD face when interacting with objects in their environment. We recruited 60 children with probable DCD and 61 children without DCD and measured perceptions of heaviness and fingertip force rate application when interacting with objects which varied in their apparent weight. If deficits in sensorimotor prediction do underpin the broad-ranging motor difficulties seen in DCD, we would expect to see a reduced effect of visual size cues on fingertip force rates and illusory misperceptions of object heaviness. We found no evidence of differences in any metrics of sensorimotor prediction between children with (n = 46) and without DCD (n = 61). Furthermore, there was no correlation between any metrics of sensorimotor prediction and motor performance (as assessed by the standard diagnostic movement assessment battery). Illusory misperceptions of object weight also did not appear to differ between groups. These findings suggest that issues with sensorimotor prediction are unlikely to affect the performance of simple real-world movements in those with DCD.

Strongyloides hyperinfection syndrome precipitated by immunosuppressive therapy for rheumatoid arthritis and COVID-19 pneumonia.

The COVID-19 pandemic has posed clinical and public health challenges worldwide. The use of corticosteroids has become an evidence-based practice to reduce the hyperinflammatory process involved in severe COVID-19 disease. However, this can result in the reactivation of parasitic infestations, even with a short course. We report the case of a 64-year-old Cuban born patient who passed away from S. stercoralis hyperinfection syndrome following treatment with dexamethasone for severe COVID-19 disease on a background of prolonged immunosuppression for rheumatoid arthritis. Clinicians should be aware of the risk of strongyloidiasis as a complication of the treatment for severe COVID-19 and other immunosuppressive therapies. We recommend empiric Strongyloides treatment for those who are from, or who have accumulated risk by travelling to endemic areas, and are being treated with corticosteroids for severe COVID-19 disease.

Type 2 innate lymphoid cells are protective against hepatic ischaemia/reperfusion injury.

Background and Aims: Although type 2 innate lymphoid cells (ILC2s) were originally found to be liver-resident lymphocytes, the role and importance of ILC2 in liver injury remains poorly understood. In the current study, we sought to determine whether ILC2 is an important regulator of hepatic ischaemia/reperfusion injury (IRI). Methods: ILC2-deficient mice (ICOS-T or NSG) and genetically modified ILC2s were used to investigate the role of ILC2s in murine hepatic IRI. Interactions between ILC2s and eosinophils or macrophages were studied in coculture. The role of human ILC2s was assessed in an immunocompromised mouse model of hepatic IRI. Results: Administration of IL-33 prevented hepatic IRI in association with reduction of neutrophil infiltration and inflammatory mediators in the liver. IL-33-treated mice had elevated numbers of ILC2s, eosinophils, and regulatory T cells. Eosinophils, but not regulatory T cells, were required for IL-33-mediated hepatoprotection in IRI mice. Depletion of ILC2s substantially abolished the protective effect of IL-33 in hepatic IRI, indicating that ILC2s play critical roles in IL-33-mediated liver protection. Adoptive transfer of ex vivo-expanded ILC2s improved liver function and attenuated histologic damage in mice subjected to IRI. Mechanistic studies combining genetic and adoptive transfer approaches identified a protective role of ILC2s through promoting IL-13-dependent induction of anti-inflammatory macrophages and IL-5-dependent elevation of eosinophils in IRI. Furthermore, in vivo expansion of human ILC2s by IL-33 or transfer of ex vivo-expanded human ILC2s ameliorated hepatic IRI in an immunocompromised mouse model of hepatic IRI. Conclusions: This study provides insight into the mechanisms of ILC2-mediated liver protection that could serve as therapeutic targets to treat acute liver injury. Impact and Implications: We report that type 2 innate lymphoid cells (ILC2s) are important regulators in a mouse model of liver ischaemia/reperfusion injury (IRI). Through manipulation of macrophage and eosinophil phenotypes, ILC2s mitigate liver inflammation and injury during liver IRI. We propose that ILC2s have the potential to serve as a therapeutic tool for protecting against acute liver injury and lay the foundation for translation of ILC2 therapy to human liver disease.

Testing predictive coding theories of autism spectrum disorder using models of active inference.

Several competing neuro-computational theories of autism have emerged from predictive coding models of the brain. To disentangle their subtly different predictions about the nature of atypicalities in autistic perception, we performed computational modelling of two sensorimotor tasks: the predictive use of manual gripping forces during object lifting and anticipatory eye movements during a naturalistic interception task. In contrast to some accounts, we found no evidence of chronic atypicalities in the use of priors or weighting of sensory information during object lifting. Differences in prior beliefs, rates of belief updating, and the precision weighting of prediction errors were, however, observed for anticipatory eye movements. Most notably, we observed autism-related difficulties in flexibly adapting learning rates in response to environmental change (i.e., volatility). These findings suggest that atypical encoding of precision and context-sensitive adjustments provide a better explanation of autistic perception than generic attenuation of priors or persistently high precision prediction errors. Our results did not, however, support previous suggestions that autistic people perceive their environment to be persistently volatile.

Photoinactivation and Photoablation of Porphyromonas gingivalis.

Several types of phototherapy target human pathogens and Porphyromonas gingivitis (Pg) in particular. The various approaches can be organized into five different treatment modes sorted by different power densities, interaction times, effective wavelengths and mechanisms of action. Mode 1: antimicrobial ultraviolet (aUV); mode 2: antimicrobial blue light (aBL); mode 3: antimicrobial selective photothermolysis (aSP); mode 4: antimicrobial vaporization; mode 5: antimicrobial photodynamic therapy (aPDT). This report reviews the literature to identify for each mode (a) the putative molecular mechanism of action; (b) the effective wavelength range and penetration depth; (c) selectivity; (d) in vitro outcomes; and (e) clinical trial/study outcomes as these elements apply to Porphyromonas gingivalis (Pg). The characteristics of each mode influence how each is translated into the clinic.

Participant Perceptions in a Long-term Clinical Trial of Autosomal Dominant Polycystic Kidney Disease.

Rationale & Objective: The development of new therapies for autosomal dominant polycystic kidney disease requires clinical trials to be conducted efficiently. In this study, the factors affecting the recruitment and retention of participants enrolled in a 3-year randomized controlled trial in autosomal dominant polycystic kidney disease were investigated. Study Design: Qualitative study. Setting & Participants: All participants (N=187) were invited to complete a 16-item questionnaire at the final study visit of the primary trial. Participants were recruited to complete a semistructured interview using purposeful sampling according to age, self-reported gender, and randomization group. Analytical Approach: Descriptive statistics were used for demographic data and questionnaires. The interview transcripts underwent inductive thematic coding. Results: One hundred and forty-six of the 187 randomized participants (79%) completed the post-trial questionnaire, and 31 of the 187 participants (21%) completed the interview. Most participants (94%) rated their global satisfaction with the trial as high (a score of 8 or more out of 10). Altruism, knowledge gain, and access to new treatments were the main motivators for recruitment. The main reasons for considering leaving the study were concerns about the risk of intervention and family or work issues. Strategies that favored retention included flexibility in attending different study sites, schedule flexibility, staff interactions, and practical support with parking and reminders. The main burden was time away from work with lost wages, and burden associated with magnetic resonance imaging scans and 24-hour urine output collections. Limitations: The study population was restricted to participants in a single nondrug clinical trial, and the results could be influenced by selection and possible social desirability bias. Conclusions: Participants reported high levels of satisfaction that occurred as a function of the trial meeting participants' expectations. Furthermore, retention was a balance between the perceived benefits and burden of participation. Consideration of these perspectives in the design of future clinical trials will improve their efficiency and conduct. Plain-Language Summary: Advances in the clinical practice of autosomal dominant polycystic kidney disease (ADPKD) require affected individuals to voluntarily participate in long-term multicenter randomized controlled trials (RCTs). In this qualitative post hoc study of a 3-year RCT of increased water intake in ADPKD, altruism, knowledge gain, and access to a nondrug treatment positively influenced the decision to volunteer. Ongoing participation was enabled by building flexibility into the study protocol and staff prioritizing a participant's needs during study visits. Although participants completed the required tests, most were considered burdensome. This study highlights the importance of incorporating protocol flexibility into trial design; the preference for interventions with a low risk of adverse effects; and the urgent requirement for robust surrogate noninvasive biomarkers to enable shorter RCTs in ADPKD.