Time-Limited Trials Among Critically Ill Patients With Advanced Medical Illnesses to Reduce Nonbeneficial Intensive Care Unit Treatments: Protocol for a Multicenter Quality Improvement Study.

BackgroundInvasive intensive care unit (ICU) treatments for patients with advanced medical illnesses and poor prognoses may prolong suffering with minimal benefit. Unfortunately, the quality of care planning and communication between clinicians and critically ill patients and their families in these situations are highly variable, frequently leading to overutilization of invasive ICU treatments. Time-limited trials (TLTs) are agreements between the clinicians and the patients and decision makers to use certain medical therapies over defined periods of time and to evaluate whether patients improve or worsen according to predetermined clinical parameters. For patients with advanced medical illnesses receiving aggressive ICU treatments, TLTs can promote effective dialogue, develop consensus in decision making, and set rational boundaries to treatments based on patients' goals of care.ObjectiveThe aim of this study will be to examine whether a multicomponent quality-improvement strategy that uses protocoled TLTs as the default ICU care-planning approach for critically ill patients with advanced medical illnesses will decrease duration and intensity of nonbeneficial ICU care without changing hospital mortality.MethodsThis study will be conducted in medical ICUs of three public teaching hospitals in Los Angeles County. In Aim 1, we will conduct focus groups and semistructured interviews with key stakeholders to identify facilitators and barriers to implementing TLTs among ICU patients with advanced medical illnesses. In Aim 2, we will train clinicians to use protocol-enhanced TLTs as the default communication and care-planning approach in patients with advanced medical illnesses who receive invasive ICU treatments. Eligible patients will be those who the treating ICU physicians consider to be at high risk for nonbeneficial treatments according to guidelines from the Society of Critical Care Medicine. ICU physicians will be trained to use the TLT protocol through a curriculum of didactic lectures, case discussions, and simulations utilizing actors as family members in role-playing scenarios. Family meetings will be scheduled by trained care managers. The improvement strategy will be implemented sequentially in the three participating hospitals, and outcomes will be evaluated using a before-and-after study design. Key process outcomes will include frequency, timing, and content of family meetings. The primary clinical outcome will be ICU length of stay. Secondary outcomes will include hospital length of stay, days receiving life-sustaining treatments (eg, mechanical ventilation, vasopressors, and renal replacement therapy), number of attempts at cardiopulmonary resuscitation, frequency of invasive ICU procedures, and disposition from hospitalization.ResultsThe study began in August 2017. The implementation of interventions and data collection were completed at two of the three hospitals. As of September 2019, the study was at the postintervention stage at the third hospital. We have completed focus groups with physicians at each medical center (N=29) and interviews of family members and surrogate decision makers (N=18). The study is expected to be completed in the first quarter of 2020, and results are expected to be available in mid-2020.ConclusionsThe successful completion of the aims in this proposal may identify a systematic approach to improve communication and shared decision making and to reduce nonbeneficial invasive treatments for ICU patients with advanced medical illnesses.International registered report identifier (irrid)DERR1-10.2196/16301

Tinnitus suppression by electric stimulation of the auditory nerve

Electric stimulation of the auditory nerve via a cochlear implant (CI) has been observed to suppress tinnitus, but parameters of an effective electric stimulus remain unexplored. Here we used CI research processors to systematically vary pulse rate, electrode place, and current amplitude of electric stimuli, and measure their effects on tinnitus loudness and stimulus loudness as a function of stimulus duration. Thirteen tinnitus subjects who used CIs were tested, with nine (70%) being “Responders” who achieved greater than 30% tinnitus loudness reduction in response to at least one stimulation condition and the remaining four (30%) being “Non-Responders” who had less than 30% tinnitus loudness reduction in response to any stimulus condition tested. Despite large individual variability, several interesting observations were made between stimulation parameters, tinnitus characteristics, and tinnitus suppression. If a subject's tinnitus was suppressed by one stimulus, then it was more likely to be suppressed by another stimulus. If the tinnitus contained a “pulsating” component, then it would be more likely suppressed by a given combination of stimulus parameters than tinnitus without these components. There was also a disassociation between the subjects' clinical speech processor and our research processor in terms of their effectiveness in tinnitus suppression. Finally, an interesting dichotomy was observed between loudness adaptation to electric stimuli and their effects on tinnitus loudness, with the Responders exhibiting higher degrees of loudness adaptation than the Non-Responders. Although the mechanisms underlying these observations remain to be resolved, their clinical implications are clear. When using a CI to manage tinnitus, the clinical processor that is optimized for speech perception needs to be customized for optimal tinnitus suppression

Can Preschoolers be Health Messengers to Promote Breast Health among Chinese Americans?

Women’s limited knowledge about breast cancer screening (BCS), combined with differences in Eastern and Western disease prevention concepts, may contribute to late-stage breast cancer diagnosis among minorities. Children can be conduits of knowledge transfer to adults. This pilot study tested the use of a culturally-tailored theatrical preschool performance in increasing Chinese American women’s knowledge of BCS guidelines. Chinese preschool children relayed BCS guidelines through a culturally-tailored theatrical performance. Data were collected from 177 Chinese American women (84% foreign-born) who completed pre- and post-performance surveys. Findings suggested that promoting BCS guidelines through a culturally-tailored preschool theatrical performance significantly increased participants’ knowledge of the guidelines. Interventions involving young children as change agents to deliver simple health messages such as BCS guidelines are feasible and promising to increase knowledge and desired behavioral change within the target population. Further empirical investigations are warranted in larger randomized controlled trials

Interprofessional Intervention to Improve Geriatric Consultation Timing on an Acute Medical Service

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147184/1/jgs15582_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147184/2/jgs15582.pd

Clinical actionability of comprehensive genomic profiling for management of rare or refractory cancers

Background. The frequency with which targeted tumor sequencing results will lead to implemented change in care is unclear. Prospective assessment of the feasibility and limitations of using genomic sequencing is critically important. Methods. A prospective clinical study was conducted on 100 patients with diverse-histology, rare, or poor-prognosis cancers to evaluate the clinical actionability of a Clinical Laboratory Improvement Amendments (CLIA)-certified, comprehensive genomic profiling assay (FoundationOne), using formalin-fixed, paraffin-embedded tumors. The primary objectives were to assess utility, feasibility, and limitations of genomic sequencing for genomically guided therapy or other clinical purpose in the setting of a multidisciplinary molecular tumor board. Results. Of the tumors from the 92 patients with sufficient tissue, 88 (96%) had at least one genomic alteration (average 3.6, range 0–10). Commonly altered pathways included p53 (46%), RAS/RAF/MAPK (rat sarcoma; rapidly accelerated fibrosarcoma; mitogen-activated protein kinase) (45%), receptor tyrosine kinases/ligand (44%), PI3K/AKT/mTOR (phosphatidylinositol-4,5-bisphosphate 3-kinase; protein kinase B; mammalian target of rapamycin) (35%), transcription factors/regulators (31%), and cell cycle regulators (30%). Many low frequency but potentially actionable alterations were identified in diverse histologies. Use of comprehensive profiling led to implementable clinical action in 35% of tumors with genomic alterations, including genomically guided therapy, diagnostic modification, and trigger for germline genetic testing. Conclusion. Use of targeted next-generation sequencing in the setting of an institutional molecular tumor board led to implementable clinical action in more than one third of patients with rare and poor-prognosis cancers. Major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access. Early and serial sequencing in the clinical course and expanded access to genomically guided early-phase clinical trials and targeted agents may increase actionability. Implications for Practice: Identification of key factors that facilitate use of genomic tumor testing results and implementation of genomically guided therapy may lead to enhanced benefit for patients with rare or difficult to treat cancers. Clinical use of a targeted next-generation sequencing assay in the setting of an institutional molecular tumor board led to implementable clinical action in over one third of patients with rare and poor prognosis cancers. The major barriers to implementation of genomically guided therapy were clinical status of the patient and drug access both on trial and off label. Approaches to increase actionability include early and serial sequencing in the clinical course and expanded access to genomically guided early phase clinical trials and targeted agents

Self-assembly of an imidazolate-bridged FeIII/CuII heterometallic cage

A rare, discrete, mixed-valent, heterometallic Fe(III)/Cu(II) cage, [CuFeL](ClO)χ solvent (HL = tris{[2-{(imidazole-4-yl)methylidene}amino]ethyl} amine), was designed and synthesized via metal-ion-directed self-assembly with neutral tripodal metalloligands. The formation of this coordination cage was demonstrated by X-ray crystallography, ESI mass spectrometry, FT-IR, and UV-vis-NIR spectroscopy

Haploinsufficient Bmp4 ocular phenotypes include anterior segment dysgenesis with elevated intraocular pressure

BACKGROUND: Glaucoma is a blinding disease usually associated with high intraocular pressure (IOP). In some families, abnormal anterior segment development contributes to glaucoma. The genes causing anterior segment dysgenesis and glaucoma in most of these families are not identified and the affected developmental processes are poorly understood. Bone morphogenetic proteins (BMPs) participate in various developmental processes. We tested the importance of Bmp4 gene dosage for ocular development and developmental glaucoma. RESULTS: Bmp4(+/-) mice have anterior segment abnormalities including malformed, absent or blocked trabecular meshwork and Schlemm's canal drainage structures. Mice with severe drainage structure abnormalities, over 80% or more of their angle's extent, have elevated IOP. The penetrance and severity of abnormalities is strongly influenced by genetic background, being most severe on the C57BL/6J background and absent on some other backgrounds. On the C57BL/6J background there is also persistence of the hyaloid vasculature, diminished numbers of inner retinal cells, and absence of the optic nerve. CONCLUSIONS: We demonstrate that heterozygous deficiency of BMP4 results in anterior segment dysgenesis and elevated IOP. The abnormalities are similar to those in human patients with developmental glaucoma. Thus, BMP4 is a strong candidate to contribute to Axenfeld-Rieger anomaly and other developmental conditions associated with human glaucoma. BMP4 also participates in posterior segment development and wild-type levels are usually critical for optic nerve development on the C57BL/6J background. Bmp4(+/-) mice are useful for studying various components of ocular development, and may allow identification of strain specific modifiers affecting a variety of ocular phenotypes

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health

The “Narratives” fMRI dataset for evaluating models of naturalistic language comprehension

The “Narratives” collection aggregates a variety of functional MRI datasets collected while human subjects listened to naturalistic spoken stories. The current release includes 345 subjects, 891 functional scans, and 27 diverse stories of varying duration totaling ~4.6 hours of unique stimuli (~43,000 words). This data collection is well-suited for naturalistic neuroimaging analysis, and is intended to serve as a benchmark for models of language and narrative comprehension. We provide standardized MRI data accompanied by rich metadata, preprocessed versions of the data ready for immediate use, and the spoken story stimuli with time-stamped phoneme- and word-level transcripts. All code and data are publicly available with full provenance in keeping with current best practices in transparent and reproducible neuroimaging