Reducing paediatric unintended extubation: A standardized bundle approach.

BACKGROUND: Unintended extubation (UE) is a serious risk associated with endotracheal intubation. In the paediatric population, UE can lead to significant patient harm. On average, each UE increases ICU and hospital length of stay by 5.5 and 6.5 days respectively and costs an additional $36 000. The international benchmark rate of UE for quality analysis cited in the literature is <1 per 100 ventilator days. The United States organization Solutions for Patient Safety (SPS) developed and introduced a bundle to reduce UE with a goal of ≤0.95 per 100 ventilator days. AIM: The aim of this quality improvement project was to determine the baseline rate of UE in a 20-bed mixed medical/surgical PICU in the Pacific Northwest of the United States, implement the SPS bundle for UE prevention, and assess adherence to the bundle, and subsequent rate of UE. STUDY DESIGN: The IHI Model for Improvement Plan-Do-Study-Act (PDSA) was used to guide the development, implementation, and assessment of the SPS UE Bundle standardizing the management of endotracheal tubes. Adherence to the bundle was measured through peer-to-peer audits. Rates of adherence and UE were monitored on line charts. RESULTS: Baseline rate of UE was 1.83 per 100 ventilator days; 23 weeks post implementation of the bundle the rate of UE was reduced to 0.38 UE per 100 ventilator days, F(7, 9) = 4.685, p = 0.027. The mean bundle adherence was 92%. CONCLUSIONS: This quality improvement initiative confirms that high adherence to the SPS UE Bundle may significantly reduce rates of UE in PICU settings. RELEVANCE TO CLINICAL PRACTISE: Use of the SPS evidence-based discrete UE bundle and high adherence to the bundle can standardize practise and may reduce unintended extubation in the paediatric population.

A Clinical Educational Intervention to Increase HPV Vaccination Rates Among Pediatric Patients Through Enhanced Recommendations.

INTRODUCTION: The human papillomavirus (HPV) causes largely preventable cancers by completing a vaccination series. However, pediatric HPV vaccination rates remain low. Current evidence indicates that integrating five factors creates a high-quality recommendation associated with higher HPV vaccination rates. This quality improvement project aimed to evaluate the impact of an educational intervention to improve the quality of providers' recommendations and subsequent vaccination rates. METHOD: Using the Squire 2.0 Guidelines, clinical staff were observed during well-child visits (aged 11-12 years) before and after the intervention across three Plan-Do-Study-Act cycles. RESULTS: Thirty-nine encounters with mostly (n = 31; 80%) families of color. The quality of vaccine recommendations was improved after the intervention; however, vaccination rates did not increase for the 39 patients. Providers' delivery approach (presumptive vs. conversational) did increase vaccination rates. DISCUSSION: Providers' delivery style appears to be important when making HPV vaccine recommendations.

A Service Evaluation of Prehospital Blood Transfusion by Critical Care Paramedics in British Columbia, Canada.

Early administration of blood products is emerging as best practice in selected trauma and medical patients. Blood products carried by critical care transport (CCT) teams are sometimes the first available to critically ill and injured patients. The purpose of this research was to evaluate the introduction of prehospital transfusion into a paramedic-led CCT program in Canada. A retrospective review of electronic patient care records for all patients who received a prehospital transfusion of uncrossmatched group O packed red blood cells between February 10, 2019, and September 30, 2020, was conducted. Forty-eight patients received a prehospital transfusion. The median age of the patients was 44 years, 81.3% were male, and most patients were victims of blunt trauma. Packed red blood cells were associated with a significant increase in systolic blood pressure (P < .001) and mean arterial pressure (P < .001), a decrease in shock index (P < .001), and a reduction in the time to first transfusion, with minimal waste, no patient-related adverse events, and complete traceability. The results of this service evaluation demonstrate the successful introduction of prehospital transfusion into a paramedic-led CCT program. Further prospective research is needed to assess the impact of such a protocol in this patient population.

Prehospital Decompression of Pneumothorax: A Systematic Review of Recent Evidence.

INTRODUCTION: Pneumothorax remains an important cause of preventable trauma death. The aim of this systematic review is to synthesize the recent evidence on the efficacy, patient outcomes, and adverse events of different chest decompression approaches relevant to the out-of-hospital setting. METHODS: A comprehensive literature search was performed using five databases (from January 1, 2014 through June 15, 2020). To be considered eligible, studies required to report original data on decompression of suspected or proven traumatic pneumothorax and be considered relevant to the prehospital context. They also required to be conducted mostly on an adult population (expected more than ≥80% of the population ≥16 years old) of patients. Needle chest decompression (NCD), finger thoracostomy (FT), and tube thoracostomy were considered. No meta-analysis was performed. Level of evidence was assigned using the Harbour and Miller system. RESULTS: A total of 1,420 citations were obtained by the search strategy, of which 20 studies were included. Overall, the level of evidence was low. Eleven studies reported on the efficacy and patient outcomes following chest decompression. The most studied technique was NCD (n = 7), followed by FT (n = 5). Definitions of a successful chest decompression were heterogeneous. Subjective improvement following NCD ranged between 18% and 86% (n = 6). Successful FT was reported for between 9.7% and 32.0% of interventions following a traumatic cardiac arrest. Adverse events were infrequently reported. Nine studies presented only on anatomical measures with predicted failure and success. The mean anterior chest wall thickness (CWT) was larger than the lateral CWT in all studies except one. The predicted success rate of NCD ranged between 90% and 100% when using needle >7cm (n = 7) both for the lateral and anterior approaches. The reported risk of iatrogenic injuries was higher for the lateral approach, mostly on the left side because of the proximity with the heart. CONCLUSIONS: Based on observational studies with a low level of evidence, prehospital NCD should be performed using a needle >7cm length with either a lateral or anterior approach. While FT is an interesting diagnostic and therapeutic approach, evidence on the success rates and complications is limited. High-quality studies are required to determine the optimal chest decompression approach applicable in the out-of-hospital setting.

Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis.

BACKGROUND: Based on the 2018 update of the Surviving Sepsis Campaign, the Committee for Quality Improvement of the NHSs of England recommended the instigation of the elements of the 'Sepsis-6 bundle' within 1 hour to adult patients screened positive for sepsis. This bundle includes a bolus infusion of 30 mL/kg crystalloids in the ED. Besides the UK, both in the USA and Australia, compliance with similar 1-hour targets became an important quality indicator. However, the supporting evidence may neither be contemporaneous nor necessarily valid for emergency medicine settings. METHOD: A systematic review was designed and registered at PROSPERO to assess available emergency medicine/prehospital evidence published between 2012 and 2020, investigating the clinical benefits associated with a bolus infusion of a minimum 30 mL/kg crystalloids within 1 hour to adult patients screened positive for sepsis. Due to the small number of papers that addressed this volume of fluids in 1 hour, we expanded the search to include studies looking at 1-6 hours. RESULTS: Seven full-text articles were identified, which investigated various aspects of the fluid resuscitation in adult sepsis. However, none answered completely to the original research question aimed to determine either the effect of time-to-crystalloids or the optimal fluid volume of resuscitation. Our findings demonstrated that in the USA/UK/Australia/Canada, adult ED septic patients receive 23-43 mL/kg of crystalloids during the first 6 hours of resuscitation without significant differences either in mortality or in adverse effects. CONCLUSION: This systematic review did not find high-quality evidence supporting the administration of 30 mL/kg crystalloid bolus to adult septic patients within 1 hour of presentation in the ED. Future research must investigate both the benefits and the potential harms of the recommended intervention.

Structured simulations improves students' knowledge acquisition and perceptions of teaching effectiveness: A quasi-experimental study.

AIMS: To determine the effect of adding structured simulation to a traditional classroom lecture format on students' knowledge acquisition and their evaluation of faculty teaching effectiveness, compared to traditional classroom lectures alone. BACKGROUND: There is a critical lack of high-quality clinical placements/experiences in nursing education, particularly in clinical specialty populations, such as paediatrics. Simulation has been shown to help students practice in a safe environment. However, less is known about the outcomes of embedding simulation in didactic class sessions or classroom lectures. Additionally, data on the impact of simulation as a teaching pedagogy on faculty teaching effectiveness is limited. DESIGN: Post-test, nonequivalent control group quasi-experimental study. METHODS: Students in two prelicensure nursing programs participated in a 10-week term paediatric nursing course taught by the same faculty member on two different campuses. The students at one campus, designated as the control group (n = 43), received four hours of traditional, lecture-only, instructions. The group at a second campus, the intervention group (n = 44), received the same lectures with added structured simulations. Students' knowledge acquisition and their evaluation of faculty teaching effectiveness were measured in both groups using the same standardised assessment measures. The CONSORT checklist was followed. RESULTS: Students' knowledge acquisition scores and their evaluation scores of faculty teaching effectiveness were significantly higher in the intervention (simulation) group compared to the control group. A significantly higher number of students in the simulation group scored above the national average Nursing Care of Children score as compared to students in the control group. CONCLUSIONS: Integrating simulation with didactic instruction enhanced students' knowledge acquisition and improved their opinion of faculty teaching effectiveness. RELEVANCE TO CLINICAL PRACTICE: Augmenting lecture with simulation may provide students with learning experiences that they may not have during clinical rotation due to a lack of paediatric clinical placement sites and differences between sites.

The moderating role of spirituality on quality of life and depression among adolescents with spina bifida.

AIM: To investigate the relationships between spirituality, somatic symptom distress/severity, depressive symptoms and quality of life (QOL) for adolescents diagnosed with spina bifida (SB). DESIGN: Exploratory, cross-sectional design. METHODS: Fifty-eight adolescents with SB in southern California were recruited during routine visits to a multidisciplinary clinic at a healthcare university from January 2016-January 2017. Each adolescent completed a series of self-report measures, including the System of Belief Inventory, Somatic Symptom Scale, Patient Health Questionnaire and Pediatric Quality of Life Inventory. Path analysis was performed to examine regression coefficients for each direct and indirect effect. RESULTS: The mediation-moderation analysis showed that depressive symptoms fully mediated the relationship between symptom distress and QOL (B = 0.029 [0.014], CI [0.007, 0.061]) and higher levels of spirituality moderated the relationship between depressive symptoms and QOL (B = 0.052, p = .018). Spirituality was higher for adolescents with greater symptom severity; including shunt status Welch's F(1, 53.689) = 4.174, p = .046, level of lesion F(2,57) = 3.382, p = .041, and ambulation status F(3, 57) = 2.920, p = .042. CONCLUSION: Adolescents with SB who had greater levels of symptom distress experienced significantly higher levels of depressive symptoms and a lower QOL. Contrary to our expectations, adolescents with greater levels of spirituality had a lower QOL when depressive symptoms were mild/moderate, but no differences were noted when depressive symptoms were severe. IMPACT: This study examined the relationship between spirituality and quality of life (QOL) in adolescents with spina bifida, who were experiencing different levels of depressive symptoms and symptom distress/severity. Depressive symptoms appeared to have a more profound effect on QOL than spirituality. Accordingly, we recommend that healthcare professionals actively screen for depressive symptoms when assessing these adolescents and their physical symptoms/distress levels.

Antibiotics administered within 1 hour to adult emergency department patients screened positive for sepsis: a systematic review.

OBJECTIVE: The 2018 Surviving Sepsis Campaign update recommended instigating the Sepsis-6 bundle within 1 h; however, the supporting evidence is weak. The objective was to systematically review the literature to determine whether there is mortality benefit (hospital or 28/30-day survival) associated with administration of antibiotics <1 h to adult emergency department (ED) patients screened positive for sepsis using systemic inflammatory response system criteria. METHODS: A systematic review and meta-analysis were conducted. Embase, CINAHL, Medline, Pubmed, Cochrane Library and grey literature were searched for articles published between 2012 and 2019. RESULTS: From 232 identified articles, seven met the inclusion criteria. Due to the small number of articles that fit the inclusion criteria and the considerable heterogeneity (I = 92.6%, P < 0.001), only the results of the systematic review are reported. Three of the seven studies demonstrated survival benefit for patients who screened positive for sepsis who were administered antibiotics ≤1 h after presentation to the ED. Four studies reported no statistically significant improvement in survival associated with administration of antibiotics within 1 h of ED presentation. Interestingly, two studies reported worse outcomes associated with early administration of antibiotics in patients with low acuity sepsis. CONCLUSION: There is equivocal evidence of in-hospital or 28/30-day survival benefit associated with antibiotics administered ≤1 h after presentation to the ED for patients who screened positive for sepsis. Further research is needed to identify the exact patient group, which would truly benefit from initiation of antibiotics <1 h after ED presentation.

Delirium Knowledge, Self-Confidence, and Attitude in Pediatric Intensive Care Nurses.

PURPOSE: A diagnosis of delirium places a critically ill child at risk of increased morbidity/mortality. Although delirium is common in critically ill children, only 2% of pediatric intensive care units (PICU) screen for delirium. The impediments to screening include knowledge deficits regarding delirium and delirium screening tools. The purpose of this improvement science project was two-fold. The first was to implement delirium screening in a PICU. The second was to evaluate the impact of multifaceted education on PICU nurses' delirium knowledge, self-confidence and attitude towards delirium. DESIGN & METHOD: A series of three plan-do-study-act cycles (PDSA) were used to implement this practice change. Multifaceted education was provided during the PDSA cycles. Two questionnaires were used to assess for changes in delirium knowledge, self-confidence and attitude towards delirium among PICU nurses. Analysis of variance (ANOVA) was used for data analysis. RESULTS: Forty-two PICU nurses completed a questionnaire measuring delirium knowledge, self-confidence, and attitude during each PDSA cycle. A significant increase in delirium knowledge, self-confidence, and attitude towards delirium was found after education (p = .003; p < .001; p = .036) and 3 months post implementation of delirium screening (p = .023; p < .001; p = .027) as compared to pre-education. CONCLUSION & PRACTICE IMPLICATIONS: Multifaceted education is a successful tool in improving nurses' knowledge, self-confidence and attitude regarding delirium. The use of PDSA cycles is a practical systematic method to improve quality of care. Improving knowledge, self-confidence and attitude have the potential to mitigate adverse effects of delirium in the critically ill child.

Implementation of an ST-Segment Elevation Myocardial Infarction Bypass Protocol in the Northern United Arab Emirates.

OBJECTIVE: The aim was to evaluate the translation of an ST-segment elevation myocardial infarction (STEMI) bypass protocol to the outcomes of patients with acute coronary syndrome in the Emirate of Ras al-Khaimah in the United Arab Emirates (UAE). METHODS: A prospective cohort study was conducted, which included all patients who had a prehospital 12-lead electrocardiogram (ECG) performed by ambulance crews. Analysis of those who were identified as having STEMI and who subsequently underwent percutaneous coronary intervention (PCI) was performed. RESULTS: A total of 152 patients had a 12-lead ECG performed during the pilot study period (February 24, 2016-August 31, 2016) with 118 included for analysis. Mean patient age was 52 years. There were 87 male (74%) and 31 female (26%) patients. Twenty-nine patients suffered a STEMI, and data were available for 11 who underwent PCI. There was no mortality, and no major adverse cardiac events were reported. The median door-to-balloon (D2B) time was 73 min (range 48-124), and 81% of patients had a D2B time < 90 min. Discharge data were available for six patients: All were discharged home with no impediments to rehabilitation. CONCLUSION: This pilot study has demonstrated agreement with the existing literature surrounding prehospital ECG and PCI activation in an unstudied STEMI population and in a novel clinical setting. It has demonstrated a D2B time of < 90 min in over 80% of STEMI patients, and a faster mean D2B time than self-presentations (mean 77 min vs. 113 min), with no associated mortality or major adverse cardiac events.

Delirium in the Critically Ill Child.

PURPOSE/OBJECTIVE: The purposes of this article are to describe the scientific literature on assessment, prevention, and management of delirium in critically ill children and to articulate the implications for clinical nurse specialists, in translating the evidence into practice. DESCRIPTION: A literature search was conducted in 4 databases-OvidMEDLINE, Cumulative Index to Nursing and Allied Health Literature, PsychINFO, and Web of Science-using the terms "delirium," "child," and "critically ill" for the period of 2006 to 2016. OUTCOME: The scientific literature included articles on diagnosis, prevalence, risk factors, adverse outcomes, screening tools, prevention, and management. The prevalence of delirium in critically ill children is up to 30%. Risk factors include age, developmental delay, severity of illness, and mechanical ventilation. Adverse outcomes include increased mortality, hospital length of stay, and cost for the critically ill child with delirium. Valid and reliable delirium screening tools are available for critically ill children. Prevention and management strategies include interventions to address environmental triggers, sleep disruption, integrated family care, and mobilization. CONCLUSION: Delirium is a common occurrence for the critically ill child. The clinical nurse specialist is accountable for leading the implementation of practice changes that are based on evidence to improve patient outcomes. Screening and early intervention for delirium are key to mitigating adverse outcomes for critically ill children.

Stochastic slowly adapting ionic currents may provide a decorrelation mechanism for neural oscillators by causing wander in the intrinsic period.

Oscillatory neurons integrate their synaptic inputs in fundamentally different ways than normally quiescent neurons. We show that the oscillation period of invertebrate endogenous pacemaker neurons wanders, producing random fluctuations in the interspike intervals (ISI) on a time scale of seconds to minutes, which decorrelates pairs of neurons in hybrid circuits constructed using the dynamic clamp. The autocorrelation of the ISI sequence remained high for many ISIs, but the autocorrelation of the ΔISI series had on average a single nonzero value, which was negative at a lag of one interval. We reproduced these results using a simple integrate and fire (IF) model with a stochastic population of channels carrying an adaptation current with a stochastic component that was integrated with a slow time scale, suggesting that a similar population of channels underlies the observed wander in the period. Using autoregressive integrated moving average (ARIMA) models, we found that a single integrator and a single moving average with a negative coefficient could simulate both the experimental data and the IF model. Feeding white noise into an integrator with a slow time constant is sufficient to produce the autocorrelation structure of the ISI series. Moreover, the moving average clearly accounted for the autocorrelation structure of the ΔISI series and is biophysically implemented in the IF model using slow stochastic adaptation. The observed autocorrelation structure may be a neural signature of slow stochastic adaptation, and wander generated in this manner may be a general mechanism for limiting episodes of synchronized activity in the nervous system.

Slow noise in the period of a biological oscillator underlies gradual trends and abrupt transitions in phasic relationships in hybrid neural networks.

In order to study the ability of coupled neural oscillators to synchronize in the presence of intrinsic as opposed to synaptic noise, we constructed hybrid circuits consisting of one biological and one computational model neuron with reciprocal synaptic inhibition using the dynamic clamp. Uncoupled, both neurons fired periodic trains of action potentials. Most coupled circuits exhibited qualitative changes between one-to-one phase-locking with fairly constant phasic relationships and phase slipping with a constant progression in the phasic relationships across cycles. The phase resetting curve (PRC) and intrinsic periods were measured for both neurons, and used to construct a map of the firing intervals for both the coupled and externally forced (PRC measurement) conditions. For the coupled network, a stable fixed point of the map predicted phase locking, and its absence produced phase slipping. Repetitive application of the map was used to calibrate different noise models to simultaneously fit the noise level in the measurement of the PRC and the dynamics of the hybrid circuit experiments. Only a noise model that added history-dependent variability to the intrinsic period could fit both data sets with the same parameter values, as well as capture bifurcations in the fixed points of the map that cause switching between slipping and locking. We conclude that the biological neurons in our study have slowly-fluctuating stochastic dynamics that confer history dependence on the period. Theoretical results to date on the behavior of ensembles of noisy biological oscillators may require re-evaluation to account for transitions induced by slow noise dynamics.

Patient safety education - a description and evaluation of an international, interdisciplinary e-learning programme.

Patient safety is a priority within healthcare across the globe. Delivering safer healthcare demands a system wide approach and educators have a responsibility to play a full role. This article describes how e-learning can be a means of engaging and educating an international group of critical care professionals studying at Masters level. Using online tools such as blogs, wikis and discussion boards students are introduced to quality and safety subjects and tools to help them improve care at a local level. Working together as a collaborative of different professionals has engaged the student group helping them understand their role in reducing harm and has resulted in improvements to care.

The upregulation of specific interleukin (IL) receptor antagonists and paradoxical enhancement of neuronal apoptosis due to electrode induced strain and brain micromotion.

The high mechanical mismatch between stiffness of silicon and metal microelectrodes and soft cortical tissue, induces strain at the neural interface which likely contributes to failure of the neural interface. However, little is known about the molecular outcomes of electrode induced low-magnitude strain (1-5%) on primary astrocytes, microglia and neurons. In this study we simulated brain micromotion at the electrode-brain interface by subjecting astrocytes, microglia and primary cortical neurons to low-magnitude cyclical strain using a biaxial stretch device, and investigated the molecular outcomes of induced strain in vitro. In addition, we explored the functional consequence of astrocytic and microglial strain on neural health, when they are themselves subjected to strain. Quantitative real-time PCR array (qRT-PCR Array) analysis of stretched astrocytes and microglia showed strain specific upregulation of an Interleukin receptor antagonist - IL-36Ra (previously IL-1F5), to ≈ 1018 and ≈ 236 fold respectively. Further, IL-36Ra gene expression remained unchanged in astrocytes and microglia treated with bacterial lipopolysaccharide (LPS) indicating that the observed upregulation in stretched astrocytes and microglia is potentially strain specific. Zymogram and western blot analysis revealed that mechanically strained astrocytes and microglia upregulated matrix metalloproteinases (MMPs) 2 and 9, and other markers of reactive gliosis such as glial fibrillary acidic protein (GFAP) and neurocan when compared to controls. Primary cortical neurons when stretched with and without IL-36Ra, showed a ≈ 400 fold downregulation of tumor necrosis factor receptor superfamily, member 11b (TNFRSF11b). Significant upregulation of members of the caspase cysteine proteinase family and other pro-apoptotic genes was also observed in the presence of IL-36Ra than in the absence of IL-36Ra. Adult rats when implanted with microwire electrodes showed upregulation of IL-36Ra (≈ 20 fold) and IL-1Ra (≈ 1500 fold) 3 days post-implantation (3 DPI), corroborating in vitro results, although these transcripts were drastically down regulated by ≈ 20 fold and ≈ 1488 fold relative to expression levels 3 DPI, at the end of 12 weeks post-implantation (12 WPI). These results demonstrate that IL receptor antagonists may be negatively contributing to neuronal health at acute time-points post-electrode implantation.

An epidermal growth factor receptor variant III-targeted vaccine is safe and immunogenic in patients with glioblastoma multiforme.

Conventional therapies for glioblastoma multiforme (GBM) fail to target tumor cells exclusively, such that their efficacy is ultimately limited by nonspecific toxicity. Immunologic targeting of tumor-specific gene mutations, however, may allow more precise eradication of neoplastic cells. The epidermal growth factor receptor variant III (EGFRvIII) is a consistent and tumor-specific mutation widely expressed in GBMs and other neoplasms. The safety and immunogenicity of a dendritic cell (DC)-based vaccine targeting the EGFRvIII antigen was evaluated in this study. Adults with newly diagnosed GBM, who had undergone gross-total resection and standard conformal external beam radiotherapy, received three consecutive intradermal vaccinations with autologous mature DCs pulsed with an EGFRvIII-specific peptide conjugated to keyhole limpet hemocyanin. The dose of DCs was escalated in cohorts of three patients. Patients were monitored for toxicity, immune response, radiographic and clinical progression, and death. No allergic reactions or serious adverse events were seen. Adverse events were limited to grade 2 toxicities. The maximum feasible dose of antigen-pulsed mature DCs was reached at 5.7 x 10(7) +/- 2.9 x 10(7) SD without dose-limiting toxicity. EGFRvIII-specific immune responses were evident in most patients. The mean time from histologic diagnosis to vaccination was 3.6 +/- 0.6 SD months. Median time to progression from vaccination was 6.8 months [95% confidence interval (C.I.(95)), 2.5-8.8], and median survival time from vaccination was 18.7 months (C.I.(95), 14.5-25.6). Overall median survival from time of histologic diagnosis was 22.8 months (C.I.(95), 17.5-29). This study establishes the EGFRvIII mutation as a safe and immunogenic tumor-specific target for immunotherapy.

Implanted neural interfaces: biochallenges and engineered solutions.

Neural interfaces are connections that enable two-way exchange of information with the nervous system. These connections can occur at multiple levels, including with peripheral nerves, with the spinal cord, or with the brain; in many instances, fundamental biophysical and biological challenges are shared across these levels. We review these challenges, including selectivity, stability, resolution versus invasiveness, implant-induced injury, and the host-interface response. Subsequently, we review the engineered solutions to these challenges, including electrode designs and geometry, stimulation waveforms, materials, and surface modifications. Finally, we consider emerging opportunities to improve neural interfaces, including cellular-level silicon to neuron connections, optical stimulation, and approaches to control inflammation. Overcoming the biophysical and biological challenges will enable effective high-density neural interfaces for stimulation and recording.