At home adaptive dual target deep brain stimulation in Parkinson's disease with proportional control.

Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. Continuous DBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and globus pallidus (dual target DBS) in a prospective within-participant, clinical trial in six patients with Parkinson's disease (n = 6, 55-65 years, n = 2 females). Dual target cDBS was tested for Parkinson's disease symptom control annually over 2 years, measured by motor rating scales, on time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral aDBS using a novel distributed (off-implant) architecture. In the home setting, we collected tremor and dyskinesia scores as well as individualized ß and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by Unified Parkinson's Disease Rating Scale (UPDRS) to a greater degree than either region alone (P < 0.05, linear mixed model) in the cohort. The amplitude of ß-oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (P < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artefacts and demonstrated a correlation between STN ß amplitude and DBS amplitude. Proportional plus integral control of aDBS reduced average power, while preserving UPDRS III scores in the clinic (P = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n = 3, P > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of Parkinson's disease over DBS of either the STN or globus pallidus alone. When combined with proportional plus integral aDBS, stimulation power may be reduced, while preserving the increased benefit of dual target DBS.

Assessment of efficacy and safety of dose-dense doxorubicin and cyclophosphamide (ddAC) in combination with immunotherapy in early-stage triple-negative breast cancer.

PURPOSE: This study aimed to assess safety and efficacy of a modified KEYNOTE 522 protocol, which incorporated pembrolizumab every 6 weeks, allowing for concomitant dose-dense (14 day) doxorubicin and cyclophosphamide (ddAC). By optimizing this dosing, the intention of this modified protocol was to improve pathologic complete response (pCR) rates in a population associated with a poorer prognosis. METHODS: This was a retrospective, single-center, cohort study. Patients were included if they had early stage, triple-negative breast cancer, and received at least one dose of AC. The entire cohort received neoadjuvant chemotherapy including weekly carboplatin and paclitaxel with pembrolizumab every 3 weeks for 12 weeks (4 cycles). The group then received either ddAC with pembrolizumab 400 mg every 6 weeks, or AC with pembrolizumab 200 mg every 3 weeks. The primary objective was pCR rate at time of surgery. RESULTS: This study assessed outcomes in 25 patients over 34 months. The pCR rate in the pembrolizumab, AC 3-week cohort was 64.3% versus 81.8% in the ddAC and 6-week pembrolizumab group. No pembrolizumab-associated grade 3-4 adverse events occurred in the either cohort. Despite seeing an increased incidence of grade 3-4 toxicities in the ddAC arm, this did not result in additional chemotherapy delays or dose reductions. CONCLUSION: This study demonstrated tolerability and a potential for favorable outcomes with this patient population, making this modified KEYNOTE 522 protocol a reasonable treatment approach. Larger, prospective studies are warranted to assess the feasibility of this dosing and true optimization of patient outcomes given the small sample size of this study.

Ratios of head circumference to ventricular size vary over time and predict eventual need for CSF diversion in intraventricular hemorrhage of prematurity.

PURPOSE: Intraventricular hemorrhage (IVH) of prematurity can lead to hydrocephalus, sometimes necessitating permanent cerebrospinal fluid (CSF) diversion. We sought to characterize the relationship between head circumference (HC) and ventricular size in IVH over time to evaluate the clinical utility of serial HC measurements as a metric in determining the need for CSF diversion. METHODS: We included preterm infants with IVH born between January 2000 and May 2020. Three measures of ventricular size were obtained: ventricular index (VI), Evan's ratio (ER), and frontal occipital head ratio (FOHR). The Pearson correlations (r) between the initial (at birth) paired measurements of HC and ventricular size were reported. Multivariable longitudinal regression models were fit to examine the HC:ventricle size ratio, adjusting for the age of the infant, IVH grade (I/II vs. III/IV), need for CSF diversion, and sex. RESULTS: A total of 639 patients with an average gestational age of 27.5 weeks were included. IVH grade I/II and grade III/IV patients had a positive correlation between initial HC and VI (r = 0.47, p < 0.001 and r = 0.48, p < 0.001, respectively). In our longitudinal models, patients with a low-grade IVH (I/II) had an HC:VI ratio 0.52 higher than those with a high-grade IVH (p-value < 0.001). Patients with low-grade IVH had an HC:ER ratio 12.94 higher than those with high-grade IVH (p-value < 0.001). Patients with low-grade IVH had a HC:FOHR ratio 12.91 higher than those with high-grade IVH (p-value < 0.001). Infants who did not require CSF diversion had an HC:VI ratio 0.47 higher than those who eventually did (p < 0.001). Infants without CSF diversion had an HC:ER ratio 16.53 higher than those who received CSF diversion (p < 0.001). Infants without CSF diversion had an HC:FOHR ratio 15.45 higher than those who received CSF diversion (95% CI (11.34, 19.56), p < 0.001). CONCLUSIONS: There is a significant difference in the ratio of HC:VI, HC:ER, and HC:FOHR size between patients with high-grade IVH and low-grade IVH. Likewise, there is a significant difference in HC:VI, HC:ER, and HC:FOHR between those who did and did not have CSF diversion. The routine assessments of both head circumference and ventricle size by ultrasound are important clinical tools in infants with IVH of prematurity.

Assessment of Embedded vs. Remote Pharmacist vs. Remote Student Pharmacist Outreach on Statin Prescribing.

BACKGROUND: The Statin Use in Persons with Diabetes (SUPD) measure is a Star measure by the Center for Medicare & Medicaid Services. The Duke Population Health Management Office (PHMO) has a team of pharmacists and pharmacy students who conduct targeted outreach to patients at risk of failing statin quality measures. Pharmacy services are embedded in select primary care clinics and other clinics are supported remotely. OBJECTIVE: The primary objective of this review is to compare the initiation rates of recommended statin prescriptions between embedded pharmacist vs remote pharmacist vs remote student pharmacist outreach groups, all of which have different levels of autonomy within pharmacy practice. The secondary objectives are to identify the barriers to the implementation of statin therapy and to assess the statin drugs and intensity of the statins prescribed. METHODS: A single-center, retrospective chart review was performed for SUPD patients with Medicare insurance. SUPD patients included patients 40-75 years of age, diagnosed with type 2 diabetes, and were not dispensed at least one statin medication of any intensity during the 6-month measurement period. The primary outcome was the initiation of recommended statin medications prescribed, or pended for the PCP to prescribe, for qualifying patients by embedded, remote, and remote student pharmacists. Secondary outcomes included the reasons for the non-implementation of statin recommendations, reasons statin therapy was not prescribed to patients contributing to the SUPD measure gap, and statin drug and dose prescribed for appropriateness. RESULTS: A total of 189 patients were included in the evaluation. In this study, 34.9% of the patients filled the prescribed or pended statin prescription and 83.3% of patients filled the prescribed or pended statin prescription at the recommended intensity according to the ACC/AHA guidelines, effectively closing the SUPD measure gap. The initiation rates of recommended statin prescriptions between the embedded pharmacist, remote pharmacist, and remote student pharmacist outreach were numerically different at 36.7%, 28.2%, and 36.7%, respectively, even though not statistically different (p=0.61). CONCLUSION: Remote student pharmacists' performance was equal to that of the embedded pharmacists when comparing the initiation rates of statin medications prescribed or pending the PCP's approval. The most common reason for non-implementation of statin therapy is that the statin was refused by the patient. Atorvastatin and rosuvastatin were the two most commonly prescribed statins.

Disparities in Access to Deep Brain Stimulation and Responsive Neurostimulation Approaches to Drug-Resistant Epilepsy.

BACKGROUND: Epilepsy affects 1% to 2% of the global population, and those who are resistant to medical treatment may be candidates for neuromodulation. In select populations, brain stimulation approaches including deep brain stimulation (DBS) and responsive neurostimulation (RNS) are used. Although studies have shown that patients from Black, Hispanic, lower income, and rural communities have less access to epilepsy care and have lower rates of epilepsy surgery, disparities in the use of brain stimulation for epilepsy treatment are currently not known. MATERIALS AND METHODS: We queried the US National Inpatient Sample data base from January 1, 2014 to December 31, 2019 for all patients discharged with an International Classification of Diseases (ICD) Ninth Revision or ICD Tenth Revision diagnosis of drug-resistant epilepsy. Among these patients discharged, the rates of brain stimulation treatment, including DBS and RNS, were reported in each subgroup of race, ethnicity, and insurance. To generate national estimates, all analyses were weighted. RESULTS: A total of 237,895 patients discharged with drug-resistant epilepsy were identified, of whom 4,925 (2.1%) received brain stimulation treatment for drug-resistant epilepsy. Black patients (n = 420, 0.9%, odds ratio [OR] = 0.51, 95% CI [0.40, 0.64]) were less likely to receive brain stimulation treatment than were White patients (n = 3300, 2.4%). There was no significant difference between Asian (n = 105, 2.3%, OR = 0.80, 95% CI [0.53, 1.33]) and Hispanic (n = 655, 2.6%, OR = 0.95, 95% CI [0.77, 1.17]) patients and White patients. No significant difference was observed between female (n = 2515, 2.1%, OR = 1.02, 95% CI [0.89, 1.17]) and male (n = 2410, 2.0%) patients either. Patients with Medicare (n = 1150, 1.2%, OR = 0.69, 95% CI [0.57, 0.84]) or Medicaid (n = 1150, 1.8%, OR = 0.52, 95% CI [0.44, 0.62]) were less likely to receive brain stimulation treatment than were those with private insurance as the primary payer (n = 2370, 3.9%). CONCLUSIONS: We discovered significant disparities in the use of brain stimulation treatments for drug-resistant epilepsy based on race and insurance status. More research will be required to determine the cause of these disparities.

Evaluation of alpelisib-induced hyperglycemia prophylaxis and associated risk factors in PIK3CA-mutated hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer.

PURPOSE: SOLAR-1 investigated alpelisib-fulvestrant (ALP + FLV) in patients with HR + /HER2-, PIK3CA-mutated advanced breast cancer and demonstrated a clinically significant increase in all-grade and grade (G) 3-4 hyperglycemia (HG) compared to placebo-fulvestrant. Given high rates of HG, a preventative protocol and identification of associated risk factors was implemented. METHODS: This single-center, retrospective study included patients receiving ALP + FLV. One week before ALP initiation, patients started an insulin-sensitizer. Patients had fasting plasma glucose (FPG) levels drawn day 8, 15, 28, then monthly. Primary outcome was incidence of G2-4 HG by day 28. Risk factors assessed included age, BMI, FPG, and HbA1c. Number of risk factors were compared between patients with and without HG. RESULTS: Sixteen women were included with median age of 59 years. The cohort was 69% White, 25% Black, 75% with BMI ≥ 25 kg/m2, and 50% with history of diabetes. By day 28, 9 patients (56%) had G2-4 HG, with only 3 (19%) G3 and zero G4. Patients with G2-4 HG had a median of 2 risk factors compared to only 1 if no HG (p = 0.03). 5 patients (31%) required a temporary hold of ALP and 3 (19%) required dose reduction due to HG. 13 patients permanently discontinued ALP-9 due to disease progression and 4 from an adverse event (only 1 HG). CONCLUSION: Implementation of a HG prophylaxis protocol with ALP in a single-center study demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (19% vs 36.6%). An increase in HG-associated risk factors correlated with a higher incidence of G2-4 HG.

Complications, Costs, and Healthcare Resource Utilization After Staged, Delayed, and Immediate Free-Flap Breast Reconstruction: A Longitudinal, Claims-Based Analysis.

BACKGROUND: There is a lack of consensus detailing the optimal approach to free-flap breast reconstruction when considering immediate, delayed, or staged techniques. This study compared costs, complications, and healthcare resource utilization (HCRU) across staged, delayed, and immediate free-flap breast reconstruction. PATIENTS AND METHODS: Retrospective study using MarketScan databases to identify women who underwent mastectomies and free-flap reconstructions between 2014 and 2018. Complications, costs, and HCRU [readmission, reoperation, emergency department (ED) visits] occurring 90 days after mastectomy and 90 days after free flap were compared across immediate, delayed, and staged reconstruction. RESULTS: Of 3310 women identified, 69.8% underwent immediate, 11.7% underwent delayed, and 18.5% underwent staged free-flap reconstruction. Staged reconstruction was associated with the highest rate (57.8% staged, 42.3% delayed, 32.0% immediate; p < 0.001) and adjusted relative risk [67% higher than immediate (95% CI: 49-87%; p < 0.001)] of surgical complications. Staged displayed the highest HCRU (staged 47.9%, delayed, 38.4%, immediate 25.2%; p < 0.001), with 16.5%, 30.7%, and 26.5% of staged patients experiencing readmission, reoperation, or ED visit, respectively. The adjusted probability of HCRU was 206% higher (95% CI: 156-266%; p < 0.001) for staged compared with immediate. Staged had the highest mean total cost (staged $106,443, delayed $80,667, immediate $76,756; p < 0.001) with regression demonstrating the adjusted mean cost for staged is 31% higher (95% CI: 23-39%; p < 0.001) when compared with immediate. CONCLUSIONS: Staged free-flap reconstruction is associated with increased complications, costs, and HCRU, while immediate demonstrated the lowest. The potential esthetic benefits of a staged approach should be balanced with the increased risk for adverse events after surgery.

Evaluation of Levetiracetam Dosing Strategies for Seizure Prophylaxis Following Traumatic Brain Injury.

BACKGROUND: Although levetiracetam has been increasingly used as an alternative to phenytoin for early posttraumatic seizure prophylaxis following traumatic brain injury (TBI), an optimal dosing strategy has not been elucidated. The objective of this study is to determine whether different dosing strategies of levetiracetam are associated with the incidence of early posttraumatic seizures when used as prophylaxis following TBI. METHODS: This retrospective single-center cohort study included admitted patients ≥ 18 years of age with a diagnosis of TBI and receiving levetiracetam for early posttraumatic seizure prophylaxis between July 1, 2013, and September 1, 2019. The primary outcome of this study was to evaluate three different dosing strategies of levetiracetam (≤ 1000 mg/day, 1500 mg/day, and ≥ 2000 mg/day) and associated rates of early posttraumatic seizures. Secondary outcomes were to summarize absolute total daily maintenance doses of levetiracetam among patients who experienced early posttraumatic seizures compared with those who did not, to determine the impact of three different dosing strategies on hospital length of stay and in-hospital mortality, and to assess patient-specific variables on the occurrence of posttraumatic seizures. Overlap propensity score weighting was used to address the potential for confounding. RESULTS: Of the 1287 patients who received levetiracetam for early posttraumatic seizure prophylaxis during the study time frame, 866 patients met eligibility criteria and were included in the study cohort (289 patients in the ≤ 1000 mg/day group, 137 patients in the 1500 mg/day group, and 440 patients in the ≥ 2000 mg/day group). After weighting, the cumulative incidence of early posttraumatic seizure was 2.9% in the ≤ 1000 mg/day group, 8.8% in the 1500 mg/day group, and 9% in the ≥ 2000 mg/day group. The 1500 mg/day and ≥ 2000 mg/day levetiracetam groups had a 209% and 216% increase in the subdistribution hazard of early posttraumatic seizures compared with the ≤ 1000 mg/day levetiracetam group, respectively, but these differences were not statistically significant. CONCLUSIONS: In conclusion, the results of this study demonstrate no statistically significant difference in the cumulative incidence of early posttraumatic seizures within 7 days of TBI between three different levetiracetam dosing strategies. After weighting, the ≤ 1000 mg/day levetiracetam group had the lowest rates of early posttraumatic seizures, death without seizure, and in-hospital mortality.

Conflict resolution styles and skills and variation among medical students.

BACKGROUND: Conflict is inevitable on healthcare teams, yet few professional school curricula teach or assess conflict resolution skills. Little is known about the variation in conflict resolution styles across medical students and how these styles might impact conflict resolution skills. METHODS: This is a prospective, single blinded, group randomized quasi experimental trial to assess the impact of knowing one's own conflict resolution style on conflict resolution skills in a simulated encounter. Graduating medical students completed a mandatory conflict resolution session with standardized patients acting as nurses during a transition to residency course. Coaches reviewed videotapes of the simulation, focusing on students' skills with negotiation and emotional intelligence. Retrospectively, we assessed the impact of the students knowing their conflict resolution style prior to simulation, student gender, race, and intended field of practice on conflict resolution skills as judged by coaches. RESULTS: One hundred and eight students completed the simulated conflict session. Sixty-seven students completed the TKI before the simulated patient (SP) encounter and 41 after. The most common conflict resolution style was accommodating (n = 40). Knowing one's conflict resolution style in advance of the simulation and one's identified race/ethnicity did not impact skill as assessed by faculty coaches. Students pursuing diagnosis-based specialties had higher negotiation (p = 0.04) and emotional quotient (p = 0.006) scores than those pursuing procedural specialties. Females had higher emotional quotient scores (p = 0.02). CONCLUSIONS: Conflict resolution styles vary among medical students. Male gender and future practice in a procedural specialty impacted conflict resolution skills but knowing conflict resolution style did not.

Short-Term Health Care Costs of High-Frequency Spinal Cord Stimulation for the Treatment of Postsurgical Persistent Spinal Pain Syndrome.

OBJECTIVE: High-frequency spinal cord stimulation (HF-SCS) is a treatment option for postsurgical persistent spinal pain syndrome (type 2 PSPS). We aimed to determine the health care costs associated with this therapy in a nationwide cohort. MATERIALS AND METHODS: IBM Marketscan® Research Databases were used to identify patients who underwent HF-SCS implantation from 2016 to 2019. Inclusion criteria included prior spine surgery or diagnoses of PSPS or postlaminectomy pain syndrome any time within the two years before implantation. Inpatient and outpatient service costs, medication costs, and out-of-pocket costs were collected six months before implantation (baseline) and one, three, and six months after implantation. The six-month explant rate was calculated. Costs were compared between baseline and six months after implant via Wilcoxon sign rank test. RESULTS: In total, 332 patients were included. At baseline, patients incurred median total costs of $15,393 (Q1: $9,266, Q3: $26,216), whereas the postimplant median total costs excluding device acquisition were $727 (Q1: $309, Q3: $1,765) at one month, $2,840 (Q1: $1,170, Q3: $6,026) at three months, and $6,380 (Q1: $2,805, Q3: $12,637) at six months. The average total cost was reduced from $21,410 (SD $21,230) from baseline to $14,312 (SD $25,687) at six months after implant for an average reduction of $7,237 (95% CI = $3212-$10,777, p < 0.001). The median device acquisition costs were $42,937 (Q1: $30,102, Q3: $65,880). The explant rate within six months was 3.4% (8/234). CONCLUSIONS: HF-SCS for PSPS was associated with significant decreases in total health care costs and offsets acquisition costs within 2.4 years. With the rising incidence of PSPS, it will be critical to use clinically effective and cost-efficient therapies for treatment.

Health Care Resource Utilization of High-Frequency Spinal Cord Stimulation for Treatment of Chronic Refractory Low Back Pain.

INTRODUCTION: Chronic refractory low back pain (CRLBP) is a diagnosis characterized by chronic low back pain in patients who are poor candidates for surgery and fail conservative management. High-frequency spinal cord stimulation (HF-SCS) is a new advance in neuromodulation that may be effective in treating these patients. However, the cost burden of this therapy is yet undetermined. MATERIALS AND METHODS: IBM MarketScan® (IBM, Armonk, NY) data bases were used to retrospectively identify patients with HF-SCS implantation between 2016 and 2019 in the United States. Those with low back pain diagnosis without history of surgery were included in the cohort. Cost data, including inpatient and outpatient service, medication, and out-of-pocket costs, were collected at six months before HF-SCS implantation and one, three, and six months after implantation. The explant rate within six months was evaluated. RESULTS: A total of 119 patients met the inclusion criteria. Most patients were female (73.1%) and owned commercial insurance (83.2%). Common comorbidities included inflammatory arthritis (22.7%), depression (26.1%), hypertension (44.5%), and obesity (26.1%). In the six months before HF-SCS implantation, patients incurred median total costs of $15,766 (first quartile [Q1]: $8,847; third quartile [Q3]: $24,947), whereas the postimplant median total cost excluding device acquisition was $398 (Q1: $145, Q3: $1,272) at one month, $2,569 (Q1: $823, Q3: $5,266) at three months, and $5,840 (Q1: $2,160; Q3: $14,607) at six months. The average reduction in total cost was $6,914 (95% CI: $588, $12,458, p < 0.001). The median total acquisition cost was $43,586 (Q1: $29,506, Q3: $69,426), with most coming from outpatient services. Of 88 patients with six-month continuous enrollment, two (2.3%) had device explant. CONCLUSIONS: We present an analysis using large claims data bases of the cost of HF-SCS for treating CRLBP and show that it may be associated with a significant decrease in total health care costs, offsetting device acquisition costs in 27 months. As advances in neuromodulation expand therapy options for patients, it will be important to understand their financial implications.

Assessment of Health Care Costs and Total Baclofen Use Associated With Targeted Drug Delivery for Spasticity.

BACKGROUND: Chronic spasticity causes significant impairment and financial burden. Oral baclofen, the first-line therapy, can have intolerable, dose-dependent side effects. Targeted drug delivery (TDD) through intrathecal baclofen delivers smaller amounts of baclofen into the thecal sac via an implanted infusion system. However, the health care resource utilization of patients with spasticity receiving TDD has not been studied extensively. MATERIALS AND METHODS: Adult patients who received TDD for spasticity between 2009 and 2017 were identified using the IBM MarketScan® data bases. Patients' use of oral baclofen and health care costs were examined at baseline (one year before implantation) and three years after implantation. A multivariable regression model using the generalized estimating equations method and a log link function was used to compare postimplantation costs with those at baseline. RESULTS: The study identified 771 patients with TDD for medication analysis and 576 for cost analysis. At baseline, the median costs were $39,326 (interquartile range [IQR]: $19,526-$80,679), which increased to $75,728 (IQR: $44,199-$122,676) in year 1, decreased to $27,160 (IQR: $11,896-$62,427) in year 2, and increased slightly to $28,008 (IQR: $11,771-$61,885) in year 3. In multivariable analysis, the cost was 47% higher than at baseline (cost ratio [CR] 1.47, 95% CI: 1.32-1.63) in year 1 but was 25% lower (CR 0.75, 95% CI: 0.66-0.86) in year 2 and 32% lower (CR 0.68, 95% CI: 0.59-0.79) in year 3. Before implant, 58% of patients took oral baclofen, which decreased to 24% by year 3. The median daily baclofen dose decreased from 61.8 mg (IQR: 40-86.4) before TDD to 32.8 mg (IQR: 30-65.7) three years later. CONCLUSIONS: Our findings indicate that patients who undergo TDD use less oral baclofen, potentially reducing the risk of side effects. Although total health care costs increased immediately after TDD, most likely owing to device and implantation costs, they decreased below baseline after one year. The costs of TDD reach cost neutrality approximately three years after implant, indicating its potential for long-term cost savings.

Impact of Education and Data Feedback on Antibiotic Prescribing for Urinary Tract Infections in the Emergency Department: An Interrupted Time-Series Analysis.

BACKGROUND: Urinary tract infections (UTIs) are often misdiagnosed or treated with exceedingly broad-spectrum antibiotics, leading to negative downstream effects. We aimed to implement antimicrobial stewardship (AS) strategies targeting UTI prescribing in the emergency department (ED). METHODS: We conducted a quasi-experimental prospective AS intervention outlining appropriate UTI diagnosis and management across 3 EDs, within an academic and 2 community hospitals, in North Carolina, United States. The study was divided into 3 phases: a baseline period and 2 intervention phases. Phase 1 included introduction of an ED-specific urine antibiogram and UTI guideline, education, and department-specific feedback on UTI diagnosis and antibiotic prescribing. Phase 2 included re-education and provider-specific feedback. Eligible patients included adults with an antibiotic prescription for UTI diagnosed in the ED from 13 November 2018 to 1 March 2021. Admitted patients were excluded. The primary outcome was guideline-concordant antibiotic use, assessed using an interrupted time-series regression analysis with 2-week intervals. RESULTS: Overall, 8742 distinct patients with 10 426 patient encounters were included. Ninety-two percent of all encounters (n = 9583) were diagnosed with cystitis and 8.1% with pyelonephritis (n = 843). There was an initial 15% increase in guideline-concordant antibiotic prescribing in phase 1 compared with the preintervention period (incidence rate ratio [IRR], 1.15; 95% confidence interval [CI], 1.03-1.29). A significant increase in guideline-concordant prescriptions was seen with every 2-week interval during phase 2 (IRR, 1.03; 95% CI, 1.01-1.04). CONCLUSIONS: This multifaceted AS intervention involving a guideline, education, and provider-specific feedback increased guideline-concordant antibiotic choices for treat-and-release patients in the ED.

Association of tacrolimus time-to-therapeutic range on renal dysfunction and acute cellular rejection after orthotopic heart transplantation in a high use basiliximab population.

BACKGROUND: Currently, clinicians often delay initiation of tacrolimus after orthotopic heart transplantation (OHT) to help mitigate nephrotoxicity. This study aimed to determine if there is an association between the time-to-therapeutic range (TTT) of tacrolimus, early renal dysfunction, and acute cellular rejection (ACR) after OHT. METHODS: This was a retrospective, single center study with adult patients who underwent OHT from July 2013 to April 2020. Logistic regression analysis was utilized to examine the association of TTT with new renal dysfunction after tacrolimus initiation post-OHT. RESULTS: In a study of 317 patients, the unadjusted analysis showed patients who developed new renal dysfunction after tacrolimus initiation had a numerically shorter TTT (9.5 vs. 11.0 days, P = .065), and were more likely to have supratherapeutic tacrolimus levels (56% vs. 39.2%, P = .010). When adjusted for established risk factors for renal dysfunction, TTT was significantly associated with new renal dysfunction (OR .95; 95% CI [.90, .99], P = .03). There was no association between TTT and the incidence of ACR (11.1 vs. 10.8 days, P = .64). CONCLUSION: When adjusting for known risk factors, a shorter TTT was associated with new renal dysfunction. Supratherapeutic tacrolimus levels were also associated with new renal dysfunction. There was no association between TTT and ACR in the setting of high use basiliximab induction.

Malnutrition and immune cell subsets in children undergoing kidney transplantation.

BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Gray's test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p < .001), a higher frequency of CD4 CD57 + PD1- T cells, and lower frequencies of CD57-PD1+ CD8 and CD57-PD1- CD8 T cells at 12-month transplant (p < .05 for all). CONCLUSIONS: Children with obesity have distinct immunophenotypes that may influence the tailoring of immunosuppression.

Effect of Initial Anticoagulation Targets on Bleeding and Thrombotic Complications for Patients With Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the effect of anticoagulation targets and intensity on bleeding events, thrombotic events, and transfusion requirements in patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) and continuous-infusion heparin. DESIGN: A retrospective cohort study. SETTING: At a single-center, large academic medical center. PARTICIPANTS: One hundred thirty-six critically ill patients. INTERVENTIONS: The following three therapeutic targets were implemented over time and evaluated: (1) no protocol (September 2013-August 2016): no standardized anticoagulation protocol or transfusion thresholds; (2) <50 seconds (September 2016-January 2018): standardized activated partial thromboplastin time (aPTT) goal of <50 seconds, maximum heparin infusion rate of 1,200 units/h, transfusion threshold of hemoglobin (Hgb) <8 g/dL; and (3) 40-to-50 seconds (February 2018-December 2019): aPTT goal of 40-to-50 sec, no maximum heparin infusion rate, transfusion threshold of Hgb <7 g/dL. MEASUREMENTS AND MAIN RESULTS: Continuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher exact tests. The primary endpoint, an incidence of at least 1 bleeding event, was highest in the no-protocol group though not statistically different among groups (39.3% v 26.7% v 34%, p = 0.5). Thrombotic complications were similar. The median units of packed red blood cells transfused were highest in the no-protocol group (3 v 2 v 0.5, p < 0.001). CONCLUSION: Anticoagulation protocols standardizing aPTT goals to <50 or 40-to-50 seconds may be a reasonable strategy for patients receiving venovenous ECMO for ARDS. More restrictive hemoglobin transfusion thresholds, in combination with lower aPTT targets, may be associated with a reduction in transfusion requirements.

Palliative Care Consultations in Patients with Severe Traumatic Brain Injury: Who Receives Palliative Care Consultations and What Does that Mean for Utilization?

BACKGROUND: Palliative care has the potential to improve goal-concordant care in severe traumatic brain injury (sTBI). Our primary objective was to illuminate the demographic profiles of patients with sTBI who receive palliative care encounters (PCEs), with an emphasis on the role of race. Secondary objectives were to analyze PCE usage over time and compare health care resource utilization between patients with or without PCEs. METHODS: The National Inpatient Sample database was queried for patients age ≥ 18 who had a diagnosis of sTBI, defined by using International Classification of Diseases, 9th Revision codes. PCEs were defined by using International Classification of Diseases, 9th Revision code V66.7 and trended from 2001 to 2015. To assess factors associated with PCE in patients with sTBI, we performed unweighted generalized estimating equations regression. PCE association with decision making was modeled via its effect on rate of percutaneous endoscopic gastrostomy (PEG) tube placement. To quantify differences in PCE-related decisions by race, race was modeled as an effect modifier. RESULTS: From 2001 to 2015, the proportion of palliative care usage in patients with sTBI increased from 1.5 to 36.3%, with 41.6% White, 22.3% Black, and 25% Hispanic patients with sTBI having a palliative care consultation in 2015, respectively. From 2008 to 2015, we identified 17,673 sTBI admissions. White and affluent patients were more likely to have a PCE than Black, Hispanic, and low socioeconomic status patients. Across all races, patients receiving a PCE resulted in a lower rate of PEG tube placement; however, White patients exhibited a larger reduction of PEG tube placement than Black patients. Patients using palliative care had lower total hospital costs (median $16,368 vs. $26,442, respectively). CONCLUSIONS: Palliative care usage for sTBI has increased dramatically this century and it reduces resource utilization. This is true across races, however, its usage rate and associated effect on decision making are race-dependent, with White patients receiving more PCE and being more likely to decline the use of a PEG tube if they have had a PCE.

Creating a win-win for the health system and health Profession's education: a direct observation clinical experience with feedback iN real-time (DOCENT) for low acuity patients in the emergency department.

BACKGROUND: Clinical education across the professions is challenged by a lack of recognition for faculty and pressure for patient throughput and revenue generation. These pressures may reduce direct observation of patient care provided by students, a requirement for both billing student-involved services and assessing competence. These same pressures may also limit opportunities for interprofessional education and collaboration. METHODS: An interprofessional group of faculty collaborated in a sequential quality improvement project to identify the best patients and physical location for a student teaching clinic. Patient chief complaint, use of resources, length of stay, estimated severity of illness and student participation and evaluation of the clinic was tracked. RESULTS: Clinic Optimization and Patient Care: Five hundred and thirty-two emergency department (ED) patients were seen in the first 19 months of the clinic. A clinic located near the ED allowed for patients with higher emergency severity index and greater utilization of imaging. Patients had similar or lower lengths of stay and higher satisfaction than patients who remained in the ED (p < 0.0001). In the second clinic location, from October 2016-June 2019, 644 patients were seen with a total of 667 concerns; the most common concern was musculoskeletal (50.1%). Student Interprofessional Experience: A total of 991 students participated in the clinic: 68.3% (n = 677) medical students, 10.1% (n = 100) physician assistant students, 9.7% (n = 96) undergraduate nursing students, 9.1% (n = 90) physical therapy students, and 2.8% (n = 28) nurse practitioner students. The majority (74.5%, n = 738) of student participants worked with students from other professions. More than 90% of students reported that faculty set a positive learning environment respectful of students. However, 20% of students reported that faculty could improve provision of constructive feedback. Direct Observation: Direct observation of core entrustable professional activities for medical students was possible. Senior medical students were more likely to be observed generating a differential diagnosis or management plan than first year medical students. CONCLUSIONS: Creation of a DOCENT clinic in the emergency department provided opportunities for interprofessional education and observation of student clinical skills, enriching student experience without compromising patient care.

Age-related effects on thymic output and homeostatic T cell expansion following depletional induction in renal transplant recipients.

Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the repopulating T cell kinetics in kidney transplant recipients who underwent alemtuzumab induction followed by belatacept/rapamycin-based immunosuppression over 36-month posttransplantation. We focused specifically on the correlation between repopulating T cell subsets and the age of patients. Substantial homeostatic Ki67-expressing T cell proliferation was seen posttransplantation. A repertoire enriched for naïve T (TNaïve ) cells emerged posttransplantation. Analysis by generalized estimating equation linear models revealed a strong negative linear association between reconstituting TNaïve cells and advancing age. A relationship between age and persistence of effector memory cells was shown. We assessed thymic output and found an increase in the frequency of recent thymic emigrants (RTEs, CD4+ CD31+ ) at 12-month posttransplantation. Patients under 30 years of age showed significantly higher levels of CD4+ CD31+ cells than patients over 55 years of age pre- and posttransplantation. IL-7 and autologous mature dendritic cells (mDCs) induced CD57- cell proliferation. In contrast, mDCs, but not IL-7, induced CD57+ cell proliferation. This study establishes the relationship between age and thymic output during T cell homeostatic repopulation after alemtuzumab induction. Trial Registration: ClinicalTrials.gov - NCT00565773.

Relationship between antithymocyte globulin, T cell phenotypes, and clinical outcomes in pediatric kidney transplantation.

Depletional induction using antithymocyte globulin (ATG) reduces rates of acute rejection in adult kidney transplant recipients, yet little is known about its effects in children. Using a longitudinal cohort of 103 patients in the Immune Development in Pediatric Transplant (IMPACT) study, we compared T cell phenotypes after ATG or non-ATG induction. We examined the effects of ATG on the early clinical outcomes of alloimmune events (development of de novo donor specific antibody and/or biopsy proven rejection) and infection events (viremia/viral infections). Long-term patient and graft outcomes were examined using the Scientific Registry of Transplant Recipients. After ATG induction, although absolute counts of CD4 and CD8 T cells were lower, patients had higher percentages of CD4 and CD8 memory T cells with a concomitant decrease in frequency of naïve T cells compared to non-ATG induction. In adjusted and unadjusted models, ATG induction was associated with increased early event-free survival, with no difference in long-term patient or allograft survival. Decreased CD4+ naïve and increased CD4+ effector memory T cell frequencies were associated with improved clinical outcomes. Though immunologic parameters are drastically altered with ATG induction, long-term clinical benefits remain unclear in pediatric patients.