Real world performance of the 21st Century Cures Act population-level application programming interface.

OBJECTIVE: To evaluate the real-world performance of the SMART/HL7 Bulk Fast Health Interoperability Resources (FHIR) Access Application Programming Interface (API), developed to enable push button access to electronic health record data on large populations, and required under the 21st Century Cures Act Rule. MATERIALS AND METHODS: We used an open-source Bulk FHIR Testing Suite at 5 healthcare sites from April to September 2023, including 4 hospitals using electronic health records (EHRs) certified for interoperability, and 1 Health Information Exchange (HIE) using a custom, standards-compliant API build. We measured export speeds, data sizes, and completeness across 6 types of FHIR. RESULTS: Among the certified platforms, Oracle Cerner led in speed, managing 5-16 million resources at over 8000 resources/min. Three Epic sites exported a FHIR data subset, achieving 1-12 million resources at 1555-2500 resources/min. Notably, the HIE's custom API outperformed, generating over 141 million resources at 12 000 resources/min. DISCUSSION: The HIE's custom API showcased superior performance, endorsing the effectiveness of SMART/HL7 Bulk FHIR in enabling large-scale data exchange while underlining the need for optimization in existing EHR platforms. Agility and scalability are essential for diverse health, research, and public health use cases. CONCLUSION: To fully realize the interoperability goals of the 21st Century Cures Act, addressing the performance limitations of Bulk FHIR API is critical. It would be beneficial to include performance metrics in both certification and reporting processes.

Hindbrain modules differentially transform activity of single collicular neurons to coordinate movements.

Seemingly simple behaviors such as swatting a mosquito or glancing at a signpost involve the precise coordination of multiple body parts. Neural control of coordinated movements is widely thought to entail transforming a desired overall displacement into displacements for each body part. Here we reveal a different logic implemented in the mouse gaze system. Stimulating superior colliculus (SC) elicits head movements with stereotyped displacements but eye movements with stereotyped endpoints. This is achieved by individual SC neurons whose branched axons innervate modules in medulla and pons that drive head movements with stereotyped displacements and eye movements with stereotyped endpoints, respectively. Thus, single neurons specify a mixture of endpoints and displacements for different body parts, not overall displacement, with displacements for different body parts computed at distinct anatomical stages. Our study establishes an approach for unraveling motor hierarchies and identifies a logic for coordinating movements and the resulting pose.

Superior colliculus drives stimulus-evoked directionally biased saccades and attempted head movements in head-fixed mice.

Animals investigate their environments by directing their gaze towards salient stimuli. In the prevailing view, mouse gaze shifts entail head rotations followed by brainstem-mediated eye movements, including saccades to reset the eyes. These 'recentering' saccades are attributed to head movement-related vestibular cues. However, microstimulating mouse superior colliculus (SC) elicits directed head and eye movements resembling SC-dependent sensory-guided gaze shifts in other species, suggesting that mouse gaze shifts may be more flexible than has been recognized. We investigated this possibility by tracking eye and attempted head movements in a head-fixed preparation that eliminates head movement-related sensory cues. We found tactile stimuli evoke directionally biased saccades coincident with attempted head rotations. Differences in saccade endpoints across stimuli are associated with distinct stimulus-dependent relationships between initial eye position and saccade direction and amplitude. Optogenetic perturbations revealed SC drives these gaze shifts. Thus, head-fixed mice make sensory-guided, SC-dependent gaze shifts involving coincident, directionally biased saccades and attempted head movements. Our findings uncover flexibility in mouse gaze shifts and provide a foundation for studying head-eye coupling.

Soma-Targeted Imaging of Neural Circuits by Ribosome Tethering.

Neuroscience relies on techniques for imaging the structure and dynamics of neural circuits, but the cell bodies of individual neurons are often obscured by overlapping fluorescence from axons and dendrites in surrounding neuropil. Here, we describe two strategies for using the ribosome to restrict the expression of fluorescent proteins to the neuronal soma. We show first that a ribosome-tethered nanobody can be used to trap GFP in the cell body, thereby enabling direct visualization of previously undetectable GFP fluorescence. We then design a ribosome-tethered GCaMP for imaging calcium dynamics. We show that this reporter faithfully tracks somatic calcium dynamics in the mouse brain while eliminating cross-talk between neurons caused by contaminating neuropil. In worms, this reporter enables whole-brain imaging with faster kinetics and brighter fluorescence than commonly used nuclear GCaMPs. These two approaches provide a general way to enhance the specificity of imaging in neurobiology.

Integration of FHIR to Facilitate Electronic Case Reporting: Results from a Pilot Study.

Current approaches to gathering sexually transmitted infection (STI) case information for surveillance efforts are inefficient and lead to underreporting of disease burden. Electronic health information systems offer an opportunity to improve how STI case information can be gathered and reported to public health authorities. To test the feasibility of a standards-based application designed to automate STI case information collection and reporting, we conducted a pilot study where electronic laboratory messages triggered a FHIR-based application to query a patient's electronic health record for details needed for an electronic case report (eCR). Out of 214 cases observed during a one week period, 181 (84.6%) could be successfully confirmed automatically using the FHIR-based application. Data quality and information representation challenges were identified that will require collaborative efforts to improve the structure of electronic clinical messages as well as the robustness of the FHIR application.

Teaching palliative care in the intensive care unit: how to break the news.

BACKGROUND: Palliative care education is often lacking in graduate medical education curricula. Studies show that many physicians are uncomfortable discussing end-of-life issues with patients and providing palliative care to dying patients and their families. We used a case-based approach to improve resident confidence in delivering bad news, discussing poor prognoses, explaining the dying process, and providing palliative care in the intensive care unit. METHODS: The medical intensive care unit (MICU) curriculum involved a 3-pronged approach, including role modeling by the attending physician and palliative care team, tutorials, and a case-based debriefing at the end of each month-long rotation. Case-based debriefing consisted of discussions by the house officers of cases they encountered during the MICU rotation. Sessions were moderated by a staff physician trained in palliative care and a palliative care advanced practice nurse. Open-ended questions stimulated the residents' reflection on their decisions and guided the discussion pertinent to palliative care. Using a survey instrument with a 4-point Likert scale, house officers assessed themselves before and after the rotation, rating their confidence in 9 areas of palliative care. Paired t tests were used to compare the cohort's scores before and after the rotation. RESULTS: A total of 214 house officers completed prerotation and postrotation surveys from April 2007 to September 2011. After completing the course, house officers demonstrated statistically significant improvement in confidence with conducting family conferences (mean 2.6 before vs 3.1 after [P<0.001]), delivering bad news (mean 3.1 before vs 3.5 after [P<0.001]), discussing do not resuscitate orders (3.1 before vs 3.6 after [P<0.001]), discussing comfort care (mean 2.8 before vs 3.4 after [P<0.001]), discussing withdrawal of life-sustaining treatment (mean 2.6 before vs 3.2 after [P<0.001]), managing pain (mean 3.0 before vs 3.5 after [P<0.001]), managing terminal symptoms (mean 2.8 before vs 3.4 after [P<0.001]), assessing decision-making capacity (mean 2.8 before vs 3.4 after [P<0.001]), and discussing advance directives (mean 2.8 before vs 3.4 after [P<0.001]). CONCLUSION: Using a multidisciplinary team to teach a structured curriculum that includes a case-based debriefing improves house officer confidence in discussing end-of-life care and providing palliative care to patients in the intensive care setting.

Utility of the 6-minute walk test following lung transplantation.

BACKGROUND: The 6-minute walk test (6-MWT) has replaced standard cardiopulmonary exercises for the evaluation of lung disease. However, data on the utility and characteristics of the 6-MWT following lung transplant are lacking. This study aimed to determine if 6-MWT distance has a normal distribution at 6 months post-transplant and if lower 6-MWT distance was predictive of all-cause mortality. METHODS: We performed a retrospective chart review of 6-MWT data on all patients who were lung transplant recipients at Ochsner Medical Center between 2000 and 2005. Forty-nine lung transplant recipients completed a 6-MWT at 6 months following transplant. Of these 49 patients, 34 had completed both the 6-month and 12-month 6-MWT, and data from these were used to evaluate change in distance walked over time. RESULTS: The mean age was 46 ± 16 years, 57% were female, and 69% received a bilateral lung transplant. Normal distribution by Kolmogorov-Smirnov was demonstrated for 6-MWT distance at 6 months (P  =  0.873). Mean distance walked improved from 348 ± 15 m to 478 ±14 m at 12 months (P  =  0.0001). The 6-MWT distance at 6 months was not a predictor of survival (OR  =  1.002). CONCLUSIONS: Distance for the 6-MWT followed a normal distribution following lung transplant, and distances walked continued to improve for a year following transplant. Although 6-MWT distances are not a predictor of survival, other components of the test may strengthen the predictive value for morbidity and mortality post-transplant.

Single-institution study evaluating the utility of surveillance bronchoscopy after lung transplantation.

BACKGROUND: Many lung transplant physicians advocate surveillance bronchoscopy with transbronchial lung biopsy and bronchoalveolar lavage (TBB/BAL) to monitor lung recipients despite limited evidence this strategy improves outcomes. This report compares rates of infection (INF), acute rejection (AR), bronchiolitis obliterans syndrome (BOS) and survival in lung allograft recipients managed with surveillance TBB/BAL (SB) versus those with clinically indicated TBB/BAL (CIB). METHODS: We reviewed 47 consecutive recipients transplanted between March 2002 and August 2005. Of these recipients, 24 consented to a multi-center trial requiring SB and 23 were managed by our usual practice of CIB. Rates of freedom from INF, AR, BOS and survival were compared. BOS and AR were diagnosed according to published guidelines from the International Society for Heart and Lung Transplantation. RESULTS: A total of 240 TBB/BALs were performed. CIB and SB groups underwent 84 (3.7 +/- 3.4/patient) and 156 (6.5 +/- 2.0/patient) TBB/BALs, respectively. In the SB group, 54 (2.2 +/- 1.6/patient) TBB/BALs were true surveillance procedures, whereas 102 (4.2 +/- 2.3/patient) were clinically indicated. No AR episode requiring treatment was detected by true surveillance. Freedom from respiratory INF, AR, BOS and survival in the SB and CIB groups showed no significant differences. Five patients in the CIB group remained stable without requiring TBB/BAL. In the SB group, 4 previously asymptomatic patients developed pneumonia within 2 weeks of surveillance TBB/BAL. CONCLUSIONS: With no obvious advantage identified, surveillance bronchoscopy may pose a risk to stable lung transplant recipients. A multi-center, controlled trial is required to validate the utility and safety of surveillance bronchoscopy in lung transplantation.

Ganciclovir for cytomegalovirus: a call for indefinite prophylaxis in lung transplantation.

BACKGROUND: Universal ganciclovir (GCV) prophylaxis is a strategy aimed at reducing cytomegalovirus (CMV) infection and delaying the development of bronchiolitis obliterans syndrome (BOS). However, the optimal duration of GCV prophylaxis remains unclear. We report our experience with GCV prophylaxis administered indefinitely and its effect on CMV pneumonitis, BOS and survival after lung transplantation (LT). METHODS: One hundred fifty-one patients surviving >100 days after LT were analyzed. GCV was given to 130 CMV donor- or recipient-seropositive patients. Data from 90 patients who received indefinite GCV prophylaxis (IND) and 40 patients who discontinued their GCV prophylaxis (STOP) were compared. RESULTS: CMV pneumonitis occurred in 16%, 8%, 17% and 19% of patients in the D+R+, D-R+, D+R- and D-R- groups, respectively. In the STOP cohort, 15 of 40 patients developed CMV pneumonitis (median time 79 days) after GCV was stopped. Ten of these 15 patients developed BOS (median time 116 days) after discontinuing GCV. The risk of CMV pneumonitis in the STOP cohort was significantly higher when GCV prophylaxis was discontinued within the first year. Cumulative incidence of CMV pneumonitis in the IND and STOP groups at 5 years was 2% and 57%, respectively (p < 0.001). BOS-free survival and survival were similar across both groups. CONCLUSIONS: Indefinite GCV prophylaxis prevents CMV pneumonitis in 98% of LT recipients. Thirty-eight percent of patients discontinuing prophylaxis developed CMV pneumonitis, 50% of whom progressed to BOS within 1 year. Continuing ganciclovir prophylaxis indefinitely after lung transplantation should be considered.

Effect of pre-transplantation prednisone on survival after lung transplantation.

BACKGROUND: It is routine practice to discontinue corticosteroids or at least reduce the dose to or=0.42 mg/kg/m(2) per day). The LD Group also included 75 patients never prescribed steroids before lung transplantation (n = 139). RESULTS: A comparison of survival rates between LD and HD Cohorts showed better survival in the LD group, p value by log rank for LD vs HD <0.01. Other than having more emphysema patients (53/139, 40%) and fewer idiopathic pulmonary fibrosis patients (21/139, 16%) in the LD group (p < 0.01), pre-transplantation characteristics between the 2 cohorts were similar. In addition, the LD Group had more bilateral lung recipients (p < 0.01). During the first 100 days after transplantation, 20 HD (20/62) patients and 16 LD (16/139) died (p < 0.01). CONCLUSIONS: Survival in the LD Cohort was strikingly better than for patients receiving >or=0.42 mg/kg/m(2) per day. Deaths in the early post-operative period for the HD Group may be related to steroid-induced complications such as poor wound healing and serious infections. A pre-lung transplantation steroid dose adjusted for body mass index of >or=0.42 mg/kg/m(2) per day may be associated with increased complications and worse survival after lung transplantation. Further studies are warranted to confirm these results.

Coagulation in sepsis.

Activation of the coagulation cascade during invasive infection can result in purpura fulminans, with rapid progression of tissue ischemia, or may manifest as abnormal clotting indices alone. Although severe derangements in coagulation are associated with organ dysfunction and increased mortality, the contribution of coagulopathy to the pathophysiology of sepsis remains incompletely understood. Over the past decade, investigators have evaluated several therapeutic anticoagulant strategies in sepsis, and manipulation of the coagulation system has emerged as a key concept in the current management of this disease. Clinical observations during treatment of septic patients with the endogenous anticoagulant activated protein C have stimulated additional study of interactions between endothelial injury, coagulation, and inflammation. This review describes clotting abnormalities during sepsis and discusses the clinical experience with therapeutic strategies intended to oppose excessive coagulation.

Hemodynamic monitoring in acute lung injury and acute respiratory distress syndrome.

Hemodynamic monitoring of critically ill patients, especially those who have ALI or ARDS, is a widely practiced compilation of techniques that largely have not been demonstrated to improve patient outcomes. Indeed, some techniques, such as use of the PAC, may actually be harmful. It seems unlikely that monitoring devices themselves are unreasonably risky to use. Rather it seems more likely that operator errors in gathering and interpreting hemodynamic data and in selecting the appropriate treatment strategies are the culprits. There is promise that ongoing clinical trials and better provider education will soon result in evidence-based recommendations for monitoring the circulation in this patient population.

Success of lung transplantation without surveillance bronchoscopy.

BACKGROUND: No current evidence demonstrates improved survival or decreased rate of bronchiolitis obliterans syndrome (BOS) despite regularly scheduled fiberoptic bronchoscopy (FOB) with transbronchial biopsy and bronchoalveolar lavage (TBB/BAL) after lung transplantation. Reduced lung function detected with spirometry or oximetry in symptomatic and asymptomatic lung allograft recipients (LARs) may be a more appropriate indication for bronchoscopic sampling. HYPOTHESIS: Clinically indicated TBB/BAL without routine invasive surveillance sampling of the transplanted lung does not decrease survival or increase the rate of BOS in LARs. METHODS: We reviewed 91 consecutive LARs transplanted at Ochsner Clinic between January 1995 and December 1999. Clinical indications for FOB with TBB/BAL include 10% decline in forced expiratory volume in 1 second below baseline; 20% decrease in forced expiratory flow rate between 25% and 75% of the forced vital capacity; or unexplained respiratory symptoms, signs, or fever. Along with demographic and clinical data, 1-year and 3-year survival rates for these 91 LARs were compared with 5,430 LARs from the International Society for Heart and Lung Transplantation (ISHLT) Registry transplanted during the same 60-month period. Ten of the 91 patients did not survive to hospital discharge after transplantation. We divided the remaining 81 LARs into 2 subsets: Group A patients (n = 43) underwent zero to 1 TBB/BAL and Group B patients (n = 38) required more than 1 procedure. Demographic data, rejection, infection, and incidence of BOS were compared between groups. RESULTS: The 1-year and 3-year survival rates in the Ochsner LAR cohort were 85% and 73%, respectively, vs 72% and 57% in the ISHLT cohort p < 0.01. The relative risks of death in the Ochsner group at 1- and 3-years were 0.56 (0.35-0.91) and 0.66 (0.48-0.92), respectively, p < 0.05. The median (range) follow-up was 910 days (60-1,886) for Group A and 961 days (105-1,883) for Group B, p = not significant. We observed twice as many patients with cystic fibrosis and twice as many pneumonia episodes in Group B. The rate of acute rejection in each group was not statistically different. The cumulative incidence of BOS was increased in Group B at 1 year and at 3 years (5% and 56%) when compared with Group A (3% and 13%), p < 0.01. CONCLUSIONS: Based on the findings from this observational, single-institution study, clinically indicated TBB/BAL without routine surveillance sampling of the lung allograft is unlikely to pose greater risk than does regularly scheduled bronchoscopy after lung transplantation.