Clinical Decision Support for Hypertension Management in Chronic Kidney Disease: A Randomized Clinical Trial.

Importance: Chronic kidney disease (CKD) affects 37 million adults in the United States, and for patients with CKD, hypertension is a key risk factor for adverse outcomes, such as kidney failure, cardiovascular events, and death. Objective: To evaluate a computerized clinical decision support (CDS) system for the management of uncontrolled hypertension in patients with CKD. Design, Setting, and Participants: This multiclinic, randomized clinical trial randomized primary care practitioners (PCPs) at a primary care network, including 15 hospital-based, ambulatory, and community health center-based clinics, through a stratified, matched-pair randomization approach February 2021 to February 2022. All adult patients with a visit to a PCP in the last 2 years were eligible and those with evidence of CKD and hypertension were included. Intervention: The intervention consisted of a CDS system based on behavioral economic principles and human-centered design methods that delivered tailored, evidence-based recommendations, including initiation or titration of renin-angiotensin-aldosterone system inhibitors. The patients in the control group received usual care from PCPs with the CDS system operating in silent mode. Main Outcomes and Measures: The primary outcome was the change in mean systolic blood pressure (SBP) between baseline and 180 days compared between groups. The primary analysis was a repeated measures linear mixed model, using SBP at baseline, 90 days, and 180 days in an intention-to-treat repeated measures model to account for missing data. Secondary outcomes included blood pressure (BP) control and outcomes such as percentage of patients who received an action that aligned with the CDS recommendations. Results: The study included 174 PCPs and 2026 patients (mean [SD] age, 75.3 [0.3] years; 1223 [60.4%] female; mean [SD] SBP at baseline, 154.0 [14.3] mm Hg), with 87 PCPs and 1029 patients randomized to the intervention and 87 PCPs and 997 patients randomized to usual care. Overall, 1714 patients (84.6%) were treated for hypertension at baseline. There were 1623 patients (80.1%) with an SBP measurement at 180 days. From the linear mixed model, there was a statistically significant difference in mean SBP change in the intervention group compared with the usual care group (change, -14.6 [95% CI, -13.1 to -16.0] mm Hg vs -11.7 [-10.2 to -13.1] mm Hg; P = .005). There was no difference in the percentage of patients who achieved BP control in the intervention group compared with the control group (50.4% [95% CI, 46.5% to 54.3%] vs 47.1% [95% CI, 43.3% to 51.0%]). More patients received an action aligned with the CDS recommendations in the intervention group than in the usual care group (49.9% [95% CI, 45.1% to 54.8%] vs 34.6% [95% CI, 29.8% to 39.4%]; P < .001). Conclusions and Relevance: These findings suggest that implementing this computerized CDS system could lead to improved management of uncontrolled hypertension and potentially improved clinical outcomes at the population level for patients with CKD. Trial Registration: ClinicalTrials.gov Identifier: NCT03679247.

Implementation of a Scalable Online Weight Management Programme in Clinical Settings: Protocol for the PROPS 2.0 Programme (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0).

INTRODUCTION: There is an urgent need for scalable strategies for treating overweight and obesity in clinical settings. PROPS 2.0 (Partnerships for Reducing Overweight and Obesity with Patient-Centered Strategies 2.0) aims to adapt and implement the combined intervention from the PROPS Study at scale, in a diverse cross-section of patients and providers. METHODS AND ANALYSIS: We are implementing PROPS 2.0 across a variety of clinics at Brigham and Women's Hospital, targeting enrolment of 5000 patients. Providers can refer patients or patients can self-refer. Eligible patients must be ≥20 years old and have a body mass index (BMI) of ≥30 kg/m2 or a BMI of 25-29.9 kg/m2 plus another cardiovascular risk factor or obesity-related condition. After enrolment, patients register for the RestoreHealth online programme/app (HealthFleet Inc.) and participate for 12 months. Patients can engage with the programme and receive personalized feedback from a coach. Patient navigators help to enrol patients, enter updates in the electronic health record, and refer patients to additional resources. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework is guiding the evaluation. ETHICS AND DISSEMINATION: The Mass General Brigham Human Research Committee approved this protocol. An implementation guide will be created and disseminated, to help other sites adopt the intervention in the future. TRIAL REGISTRATION NUMBER: NCT0555925.

The career and research contributions of Richard R. Fay.

For over 50 years, Richard R. (Dick) Fay made major contributions to our understanding of vertebrate hearing. Much of Dick's work focused on hearing in fishes and, particularly, goldfish, as well as a few other species, in a substantial body of work on sound localization mechanisms. However, Dick's focus was always on using his studies to try and understand bigger issues of vertebrate hearing and its evolution. This article is slightly adapted from an article that Dick wrote in 2010 on the closure of the Parmly Hearing Institute at Loyola University Chicago. Except for small modifications and minor updates, the words and ideas herein are those of Dick.

Communication about distress and well-being: Epistemic and ethical considerations.

Communication about well-being and distress involves multiple stakeholders, including experts by experience (EBE), researchers, clinical practitioners, interpreters, and translators. Communication can involve a variety of discourses and languages and each of the stakeholders may employ diverging epistemologies to understand and explain experiences. These epistemologies may link to different sources of authority and be articulated using particular linguistic resources. Epistemic injustice can occur when stakeholders, intentionally or unintentionally, fail to recognise the validity of other stakeholders' ways of conceptualising and verbalising their experience of well-being and distress. Language lies at the heart of the risk of epistemic injustice involved in the process of expressing well-being and distress as seen in: 1) the interface between divergent discourses on well-being and distress (e.g., biomedical vs. spiritual); and 2) communications involving multiple linguistic resources, which can be subdivided into multi-language communications involving a) translation of assessment measures, and b) interpreted interactions. Some of the challenges of multi-language communication can be addressed by translators or interpreters who strive for conceptual equivalence. We argue, however, that all stakeholders have an important role as "epistemic brokers" in the languaging of possible epistemological differences. Effective epistemic brokering requires that all stakeholders are reflexively and critically aware of the risks of epistemic injustice inherent in multi-language communication. The article concludes with a set of prompts to help raise stakeholder awareness and reflexivity when engaging in communication about well-being and distress.

Intra- and Intersexual swim bladder dimorphisms in the plainfin midshipman fish (Porichthys notatus): Implications of swim bladder proximity to the inner ear for sound pressure detection.

The plainfin midshipman fish, Porichthys notatus, is a nocturnal marine teleost that uses social acoustic signals for communication during the breeding season. Nesting type I males produce multiharmonic advertisement calls by contracting their swim bladder sonic muscles to attract females for courtship and spawning while subsequently attracting cuckholding type II males. Here, we report intra- and intersexual dimorphisms of the swim bladder in a vocal teleost fish and detail the swim bladder dimorphisms in the three sexual phenotypes (females, type I and II males) of plainfin midshipman fish. Micro-computerized tomography revealed that females and type II males have prominent, horn-like rostral swim bladder extensions that project toward the inner ear end organs (saccule, lagena, and utricle). The rostral swim bladder extensions were longer, and the distance between these swim bladder extensions and each inner-ear end organ type was significantly shorter in both females and type II males compared to that in type I males. Our results revealed that the normalized swim bladder length of females and type II males was longer than that in type I males while there was no difference in normalized swim bladder width among the three sexual phenotypes. We predict that these intrasexual and intersexual differences in swim bladder morphology among midshipman sexual phenotypes will afford greater sound pressure sensitivity and higher frequency detection in females and type II males and facilitate the detection and localization of conspecifics in shallow water environments, like those in which midshipman breed and nest.

"Large" Tank Acoustics: How Big Is Big Enough?

In this paper, we discuss the issues encountered when trying to perform hearing experiments in water-filled tanks that are several meters in lateral extent, typically large in terms of the size of the animals under study but not necessarily so with respect to the wavelengths of interest. This paper presents measurements of pressure and particle motion fields in these "large" tanks. The observed characteristics and complexities are discussed in reference to their potential impact on the planning and interpretation of hearing experiments.

It Started in Hawai'i Kai: Reminiscences of 43 Years (and Counting) of Collaboration and Friendship.

This paper discusses the 43+ year collaboration of Arthur Popper and Richard Fay. Over these years, we have co-authored over 30 papers and 55 books. The collaboration benefits from a strong friendship that includes our spouses and children. By any measure, our collaboration must be seen as being successful. The basis for this success is, we think, twofold. First, we have very complementary and overlapping research interests. This has enabled us to tackle issues, whether in research or in planning meetings or books, from different perspectives. Second, a hallmark of our successful collaboration has been our deep and close friendship and the extension of that friendship to our spouses and children. In this paper, we discuss some of the events that have shaped our collaboration, and some of the people who have impacted our lives.

Parvulescu Revisited: Small Tank Acoustics for Bioacousticians.

Researchers often perform hearing studies on fish in small tanks. The acoustic field in such a tank is considerably different from the acoustic field that occurs in the animal's natural environment. The significance of these differences is magnified by the nature of the fish's auditory system where either acoustic pressure (a scalar), acoustic particle velocity (a vector), or both may serve as the stimulus. It is essential for the underwater acoustician to understand the acoustics of small tanks to be able to carry out valid auditory research in the laboratory and to properly compare and interpret the results of others.

Auditory Evoked Potential Audiograms Compared with Behavioral Audiograms in Aquatic Animals.

Auditory evoked potentials (AEPs) have become popular for estimating hearing thresholds and audiograms. What is the utility of these measurements? How do AEP audiograms compare with behavioral audiograms? In general, AEP measurements for fishes and marine mammals often underestimate behavioral thresholds, but comparisons are especially complicated when the AEP and behavioral measures are obtained under different acoustic conditions. There is no single representative relationship between AEP and behavioral audiograms and these audiograms should not be considered equivalent. We suggest that the most valuable comparisons are those made by the same researcher using similar acoustic conditions for both measurements.

Computerized tomography of the otic capsule and otoliths in the oyster toadfish, Opsanus tau.

The neurocranium of the toadfish (Opsanus tau) exhibits a distinct translucent region in the otic capsule (OC) that may have functional significance for the auditory pathway. This study used ultrahigh resolution computerized tomography (100 µm voxels) to compare the relative density of three sites along the OC (dorsolateral, midlateral, and ventromedial) and two reference sites (dorsal: supraoccipital crest; ventral: parasphenoid bone) in the neurocranium. Higher attenuation occurs where structural density is greater; thus, we compared the X-ray attenuations measured, which provided a measure of relative density. The maximum attenuation value was recorded for each of the five sites (x and y) on consecutive sections throughout the OC and for each of the three calcareous otoliths associated with the sensory maculae (lagena, saccule, and utricle) in the OC. All three otoliths had higher attenuations than any sites in the neurocranium. Both dorsal and ventral reference sites (supraoccipital crest and parasphenoid bone, respectively) had attenuation levels consistent with calcified bone and had relatively small, irregular variations along the length of the OC in all individuals. The lowest relative attenuations (lowest densities) occurred consistently at the three sites along the OC. In addition, the lowest attenuations measured along the OC occurred at the ventromedial site around the saccular otolith for all seven fish. The decrease in bone density along the OC is consistent with the hypothesis that there is a low-density channel in the skull to facilitate transmission of acoustic stimuli to the auditory endorgans of the ear.

Use of the swim bladder and lateral line in near-field sound source localization by fish.

We investigated the roles of the swim bladder and the lateral line system in sound localization behavior by the plainfin midshipman fish (Porichthys notatus). Reproductive female midshipman underwent either surgical deflation of the swim bladder or cryoablation of the lateral line and were then tested in a monopolar sound source localization task. Fish with nominally 'deflated' swim bladders performed similar to sham-deflated controls; however, post-experiment evaluation of swim bladder deflation revealed that a majority of 'deflated' fish (88%, seven of the eight fish) that exhibited positive phonotaxis had partially inflated swim bladders. In total, 95% (21/22) of fish that localized the source had at least partially inflated swim bladders, indicating that pressure reception is likely required for sound source localization. In lateral line experiments, no difference was observed in the proportion of females exhibiting positive phonotaxis with ablated (37%) versus sham-ablated (47%) lateral line systems. These data suggest that the lateral line system is likely not required for sound source localization, although this system may be important for fine-tuning the approach to the sound source. We found that midshipman can solve the 180 deg ambiguity of source direction in the shallow water of our test tank, which is similar to their nesting environment. We also found that the potential directional cues (phase relationship between pressure and particle motion) in shallow water differs from a theoretical free-field. Therefore, the general question of how fish use acoustic pressure cues to solve the 180 deg ambiguity of source direction from the particle motion vector remains unresolved.

Does the magnocellular octaval nucleus process auditory information in the toadfish, Opsanus tau?

Previous work on auditory processing in Opsanus tau has focused on the descending octaval nucleus; however, the magnocellular octaval nucleus receives similar inputs from the otolithic endorgans. The purpose of this study was to assess whether cells in any of the three subdivisions of the magnocellular nucleus respond to auditory frequencies and encode sound source direction. Extracellular recording sites were chosen based on anatomical landmarks, and neurobiotin injections confirmed the location of auditory sites in subdivisions of the magnocellular nucleus. In general, the auditory cells in M2 and M3 responded best to frequencies at or below 100 Hz. Most auditory cells responded well to directional stimuli presented along axes in the horizontal plane. Cells in M3 (not M2) also responded to lateral line stimulation, consistent with otolithic endorgan and lateral line inputs to M3. The convergence of auditory and lateral line inputs in M3, the lack of Mauthner cells in this species, and previous evidence that the magnocellular nucleus does not contribute to ascending auditory pathways suggest to us that the large cells of M3 may play a role in rapid behavioral responses to particle motion stimuli in oyster toadfish.

Auditory evoked potential audiometry in fish.

A recent survey lists more than 100 papers utilizing the auditory evoked potential (AEP) recording technique for studying hearing in fishes. More than 95 % of these AEP-studies were published after Kenyon et al. introduced a non-invasive electrophysiological approach in 1998 allowing rapid evaluation of hearing and repeated testing of animals. First, our review compares AEP hearing thresholds to behaviorally gained thresholds. Second, baseline hearing abilities are described and compared in 111 fish species out of 51 families. Following this, studies investigating the functional significance of various accessory hearing structures (Weberian ossicles, swim bladder, otic bladders) by eliminating these morphological structures in various ways are dealt with. Furthermore, studies on the ontogenetic development of hearing are summarized. The AEP-technique was frequently used to study the effects of high sound/noise levels on hearing in particular by measuring the temporary threshold shifts after exposure to various noise types (white noise, pure tones and anthropogenic noises). In addition, the hearing thresholds were determined in the presence of noise (white, ambient, ship noise) in several studies, a phenomenon termed masking. Various ecological (e.g., temperature, cave dwelling), genetic (e.g., albinism), methodical (e.g., ototoxic drugs, threshold criteria, speaker choice) and behavioral (e.g., dominance, reproductive status) factors potentially influencing hearing were investigated. Finally, the technique was successfully utilized to study acoustic communication by comparing hearing curves with sound spectra either under quiet conditions or in the presence of noise, by analyzing the temporal resolution ability of the auditory system and the detection of temporal, spectral and amplitude characteristics of conspecific vocalizations.

Experiments in comparative hearing: Georg von Békésy and beyond.

Georg von Békésy was one of the first comparative auditory researchers. He not only studied basilar membrane (BM) movements in a range of mammals of widely different sizes, he also worked on the chicken basilar papilla and the frog middle ear. We show that, in mammals, at least, his data do not differ from those that could be collected using modern techniques but with the same, very loud sounds. There is in all cases a major difference to frequency maps collected using low-level sounds. In contrast, the same cannot be said of his chicken data, perhaps due to the different roles played by the BM in mammals and birds. In lizards, the BM is not tuned and it is perhaps good that Békésy did not begin with those species and get discouraged in his seminal comparative work.

Specialization for underwater hearing by the tympanic middle ear of the turtle, Trachemys scripta elegans.

Turtles, like other amphibious animals, face a trade-off between terrestrial and aquatic hearing. We used laser vibrometry and auditory brainstem responses to measure their sensitivity to vibration stimuli and to airborne versus underwater sound. Turtles are most sensitive to sound underwater, and their sensitivity depends on the large middle ear, which has a compliant tympanic disc attached to the columella. Behind the disc, the middle ear is a large air-filled cavity with a volume of approximately 0.5 ml and a resonance frequency of approximately 500 Hz underwater. Laser vibrometry measurements underwater showed peak vibrations at 500-600 Hz with a maximum of 300 µm s(-1) Pa(-1), approximately 100 times more than the surrounding water. In air, the auditory brainstem response audiogram showed a best sensitivity to sound of 300-500 Hz. Audiograms before and after removing the skin covering reveal that the cartilaginous tympanic disc shows unchanged sensitivity, indicating that the tympanic disc, and not the overlying skin, is the key sound receiver. If air and water thresholds are compared in terms of sound intensity, thresholds in water are approximately 20-30 dB lower than in air. Therefore, this tympanic ear is specialized for underwater hearing, most probably because sound-induced pulsations of the air in the middle ear cavity drive the tympanic disc.

Preliminary efforts directed toward the detection of craving of illicit substances: the iHeal project.

Many behavioral interventions, whether for the management of chronic pain, overeating, medication adherence, or substance abuse, are ineffective outside of the clinic or office environments in which they are taught. This lack of utility has spawned interest in enabling technologies that are capable of detecting changes in affective state that potentially herald a transition to risky behaviors. We have therefore undertaken the preliminary development of "iHeal", an innovative constellation of technologies that incorporates artificial intelligence, continuous biophysical monitoring, wireless connectivity, and smartphone computation. In its fully realized form, iHeal can detect developing drug cravings; as a multimedia device, it can also intervene as the cravings develop to prevent drug use. This manuscript describes preliminary data related to the iHeal Project and our experience with its use.

Local acoustic particle motion guides sound-source localization behavior in the plainfin midshipman fish, Porichthys notatus.

Sound-source localization behavior was studied in the plainfin midshipman fish (Porichthys notatus) by making use of the naturally occurring phonotaxis response of gravid females to playback of the male's advertisement call. The observations took place outdoors in a circular concrete tank. A dipole sound projector was placed at the center of the tank and an 80-90 Hz tone (the approximate fundamental frequency to the male's advertisement call) was broadcast to gravid females that were released from alternative sites approximately 100 cm from the source. The phonotaxic responses of females to the source were recorded, analyzed and compared with the sound field. One release site was approximately along the vibratory axis of the dipole source, and the other was approximately orthogonal to the vibratory axis. The sound field in the tank was fully characterized through measurements of the sound pressure field using hydrophones and acoustic particle motion using an accelerometer. These measurements confirmed that the sound field was a nearly ideal dipole. When released along the dipole vibratory axis, the responding female fish took essentially straight paths to the source. However, when released approximately 90 deg to the source's vibratory axis, the responding females took highly curved paths to the source that were approximately in line with the local particle motion axes. These results indicate that the acoustic cues used by fish during sound-source localization include the axes of particle motion of the local sound field.