Administration In Adult Patients Research Articles

Improving the Timing of Acute Care Insulin Delivery.

Variations in nursing practice were observed across our hospital, a 520-bed acute care teaching facility in the northeast United States, regarding the timing and frequency of insulin administration in adult patients with diabetes. Chart audits noted that RNs administered insulin more than one hour after blood glucose results were obtained 97% of the time. In addition, insulin was given at bedtime only 37% of the time. The purpose of this quality improvement (QI) project was to improve the care of inpatients requiring insulin by implementing protocols and adjusting practice to align with best practice recommendations. The clinical nurse education specialist met with a team of staff nurses, providers, nurse leaders, and patient care technicians (PCTs) to formulate protocols and design interventions to ensure improvements in the quality of care for inpatients with diabetes. A sequence of education sessions and an online learning module were developed and assigned to nurses and PCTs to address knowledge gaps, specifically in the pharmacodynamics and safe administration of insulin, as well as how best to provide care to patients with diabetes. Monthly adherence data were disseminated to nurse leaders and educators and reviewed with clinical staff at daily safety huddles and staff meetings. Additional interventions to enhance nursing practice in caring for patients with diabetes included ensuring both bedtime insulin administration and timely insulin delivery. This project began in May 2017 and ended five years later. Two weeks after initial education sessions began in May and June 2017, the frequency of giving bedtime insulin based on the order set and according to the patient's blood glucose levels rose from 37% to 82%, and adherence to best practice protocols continued until final chart audits were performed in May 2022. The frequency of giving insulin less than one hour after obtaining blood glucose results improved from 3% to 64% between October and December 2019, and increased to a sustained level above the project's 92% goal two years later. Protocol development, targeted education, and audits with feedback led to improved care delivery for patients requiring insulin and increased nursing confidence.

EE360 Clinical and Economic Evaluation of Atezolizumab Versus Durvalumab Administration in Adult Patients with Extensive Stage Small Cell Lung Cancer

EE360 Clinical and Economic Evaluation of Atezolizumab Versus Durvalumab Administration in Adult Patients with Extensive Stage Small Cell Lung Cancer

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. Retrospective analysis. Multisite integrated health system throughout Minnesota and Wisconsin. Adult patients with lymphoma who received HDMTX as a 4-h infusion. LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Changes in Peripheral Blood Eosinophil Counts and Risk of Eosinophilic Granulomatosis with Polyangiitis Onset after Initiation of Dupilumab Administration in Adult Patients with Asthma.

The purpose of this study is to clarify the changes in peripheral blood eosinophil (PBE) counts and eosinophilic granulomatosis with polyangiitis (EGPA) onset in patients with asthma who were treated with dupilumab in clinical practice. The primary outcome of this study is to determine the onset of EGPA in patients whose PBE counts continued to rise within 6 months of dupilumab initiation (rising group) and in patients whose PBE counts peaked and subsequently declined within 6 months (peaked and declined group). As a secondary outcome, the incidence of developing EGPA in patients with PBE counts greater than 1500 cells/μL at 3 or 6 months after dupilumab administration is investigated. A total of 37 individual were enrolled (male/female = 14/23, median age = 57.0 years old). The development of EGPA was significantly more frequent in the rising group compared with the peaked and declined group (p = 0.042, effect size = 0.455, moderate association). Patients with PBE counts greater than 1500 cells/μL showed a significantly higher risk of developing EGPA (p = 0.017, effect size = 0.678, strong association). Physicians should check for the onset of EGPA by monitoring the elevation of eosinophils within 6 months after dupilumab administration, especially in patients with PBE counts greater than 1500 cells/μL at 3 months.

Perioperative ketamine administration to prevent delirium and neurocognitive disorders after surgery: a systematic review and meta-analysis.

Surgery induces high rates of cognitive disorders, persisting for up to 12 months in elderly adults. This review aimed to assess the currently debated preventive effect of perioperative ketamine on postoperative delirium and postoperative neurocognitive disorders (POND). Systematic review and meta-analysis including all randomized controlled trials investigating the effects of perioperative ketamine administration in adult patients compared to placebo or no intervention on postoperative delirium and/or POND between January 2007 and April 2022. Database searches were conducted in PubMed, Medline, Embase, Scopus, and Central. Random effects models were used to pool overall estimates. The GRADE approach was used to assess the quality of the evidence. From 1379 records screened, 14 randomized controlled trials with 1618 patients randomized met our inclusion criteria with a high level of consensus among reviewers, amongst whom 50% were at low-moderate risk of bias. There was no between-group difference in postoperative delirium [8 trials, 1265 patients, odds ratio (OR) 0.93, 95% CI (0.51-1.70), I2 =28%] and POND [5 trials, 494 patients, OR 0.52, 95% CI (0.15-1.80); I2 =78%]. There was no significant between-group difference in postoperative psychological adverse effects, level of pain, hospital length of stay, or mortality. Between-group subgroup analyses showed no difference in delirium or POND incidence according to surgical setting, ketamine dose, mode of administration, combination or not with other drug(s), and assessment timing or definition of cognitive disorders. Perioperative ketamine does not prevent postoperative delirium or POND. Significant study heterogeneity suggests that standardized measures for POND assessment and a specific focus on patients at high risk for POND should be used to improve the comparability of future studies.

WED-128 - Passive transfer of hepatitis B core antibody after intravenous immunoglobulin administration in adult patients: a retrospective review

WED-128 - Passive transfer of hepatitis B core antibody after intravenous immunoglobulin administration in adult patients: a retrospective review

Efficacy and Safety of Long-Term Romiplostim Use for Refractory Aplastic Anemia

Introduction: Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome characterized by pancytopenia and hypocellular bone marrow caused by the destruction of hematopoietic stem cells by lymphocytes. About one-third of patients with severe AA who cannot undergo allogeneic hematopoietic stem cell transplantation from a matched sibling donor are refractory to single or repeated immunosuppressive therapy courses. Romiplostim (ROMI), a thrombopoietin receptor agonist, signals and activates intracellular transcriptional pathways via the thrombopoietin receptor, resulting in stimulation of hematopoietic stem and progenitor cells. Our previous research, a phase II/III, multicenter, open-label interventional study, showed that ROMI induced the recovery of at least one lineage of blood cells in >80% of patients with refractory AA. However, data on the long-term efficacy and safety of ROMI in refractory AA beyond 52 weeks are scarce. Additionally, the pretreatment baseline factors of patients who achieve hematological response during treatment and maintain response after discontinuing ROMI are unclear. To address these issues, we report the results at the end of the extension phase (June 2020) of the aforementioned phase II/III study. Methods: We conducted a long-term follow-up analysis of the efficacy and safety of ROMI 10 μg/kg administered subcutaneously once weekly for 4 weeks (Weeks 1-4), followed by 1-step titration to 5, 10, 15, and 20 μg/kg once weekly up to 52 weeks (Weeks 5-52) depending on platelet response. The extension study was started from Week 56 after a 4-week suspension period. The patients continued to receive the same dose of ROMI they received on Week 52 until its commercially available date for the treatment of AA in the study country or the end of June 2020 (end of the extension phase), whichever occurred first. Results: Of the 31 patients enrolled in the phase II/III study, 27 completed the 53-week assessment. Twenty-five hematological responders (any cell lineage) and 2 non-responders entered the extension phase. ROMI was administered for 2 years in 23 patients, 3 years in 7 patients, and 3.5 years in 6 patients in this extension study. The median dose of ROMI was 20 μg/kg at Week 53, which was reduced to 15 μg/kg at 2 years, and 7.5 μg/kg at 3.5 years (Figure 1). Of the 2 non-responders, 1 patient showed platelet response at 2 years, which was sustained thereafter, while the other failed to respond by the end of the extension study at 103 weeks. Of the patients who failed to achieve the platelet (n=7) and erythrocyte (n=6) responses at 1 year, 3 (43%) and 1 (17%) showed responses at 2 years; the mean platelet count increased from 38.3 to 76.7 ×109/L in the 3 platelet responders, and the hemoglobin level increased from 8.0 to 9.2 g/dL in the erythrocyte responder (Figure 2). Of the 23 patients who needed blood transfusions at baseline, 4 and 2 of them still required erythrocyte and platelet transfusions at 1 year, and 4 and 5 of them did so at 2 years, respectively. Five patients remained in response after discontinuing ROMI lasting 29-111 weeks even after discontinuing treatment. These 5 patients had relatively high baseline reticulocyte counts (45.8-93.8 ×109/L, median 57.5 ×109/L) compared with the remaining 22 patients (2.7-114.7 ×109/L, median 46.5 ×109/L). The most common adverse drug reactions included headache (3 cases, 9.7%) and muscle spasms (2 cases, 6.5%); cytogenetic abnormality (-7) led to discontinuation of the study drug in 1 case. Two patients presented with chromosomal abnormalities of unknown significance, including 46,XX,t(11;17) at Week 108 and 46,XX,add(10) at Week 134. No transformation to acute myeloid leukemia or myelodysplastic syndromes occurred. Conclusions: The up to 3.5-year follow-up study of ROMI administration in adult patients with refractory AA demonstrated its safety and efficacy during the extension period. The dose of ROMI was on a downward trend during the long-term follow-up. Nearly half the patients who did not achieve platelet or erythrocyte responses to ROMI at Week 52 eventually achieved responses by continuing the administration until the end of the study, demonstrating the efficacy of prolonged ROMI administration. High reticulocyte counts at ROMI initiation may predict achievement of response after discontinuing ROMI. Further studies with larger sample sizes should confirm these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Tacrolimus Pharmacogenetics and Steady State Drug Concentrations in Cancer Patients Undergoing Allogeneic Stem Cell Transplantation

Background: Tacrolimus is the backbone of immunosuppressive therapy in patients undergoing an allogeneic stem cell transplant (SCT). Significant inter-patient variability in tacrolimus exposure exists, partly due to variations in pharmacokinetic genes. In particular, the Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines provide dosing recommendations based on CYP3A5 genotype; however, these are based on studies performed in patients undergoing solid organ transplants and receiving oral tacrolimus. We aimed to investigate the impact of CYP3A4, CYP3A5, and ABCB1 polymorphisms on intravenous (IV) tacrolimus exposure in allogeneic SCT patients.Methods: Buccal swabs were collected from allogeneic SCT patients on the day of admission (prior to transplant) between 07/03/14 and 06/22/2017. DNA was extracted using the GenElute™ Mammalian Genomic DNA Kit. A custom Ion AmpliSeq™ PGx Panel was used to genotype the samples for polymorphisms in CYP3A5 (*3, *6, *7), CYP3A4 (*1B, *22) and ABCB1 (C1236T, G2677T, C3435T), and the corresponding phenotypes were inferred based on available guidelines and literature. IV tacrolimus infusion was started at 0.03 mg/kg on day +5 post-transplant. Blood samples were drawn every 2 days, and doses were adjusted after reaching steady-state (SS), targeting a plasma concentration of 5-15 ng/mL. The primary endpoint was the prevalence of non-therapeutic concentrations at SS (4th day after starting tacrolimus) between phenotypes, which was compared using the Fisher's exact test. Univariate and multivariable logistic regression analyses were performed to explore demographic variables and gene phenotypes associated with prevalence of non-therapeutic SS concentrations. Student's t-test was used to compare mean tacrolimus SS concentration between phenotypes.Results: The study included 63 adult patients with a mean age of 54 (range 25-78) years. The majority were male (65%), 73% were Caucasian and 22% were African American. The inferred phenotype frequencies for CYP3A5, CYP3A4 and ABCB1 are shown in Table 1. No patient (0%) had an initial sub-therapeutic tacrolimus SS concentration (< 5 ng/mL), whereas 28.6% (n=18) and 71.4% (n=45) had an initial therapeutic and supra-therapeutic tacrolimus SS concentration (> 15 ng/mL), respectively. The prevalence of supra-therapeutic tacrolimus SS concentration was 80% in CYP3A4 NM/IMs and 43% among CYP3A4 RMs (p=0.016). Approximately 87% of carriers of at least one copy of the loss of function allele for ABCB1 C2677T (2677 CT and 2677 TT) had a supra-therapeutic tacrolimus SS concentration compared to 50% in non-carriers (2677 CC, p=0.004). Alternatively, there were no significant differences in the prevalence of supra-therapeutic SS concentrations by CYP3A5, ABCB1 C1236T, and ABCB1 C3435T genotypes (p>0.05). Univariate logistic regression analysis identified Caucasian race (p=0.009), CYP3A4 (p=0.011), and ABCB1 C2677T (p=0.003) as significantly associated with supra-therapeutic SS concentrations (Table 2). Of these, only ABCB1 C2677T was retained in the multivariable model (p=0.004). The mean tacrolimus SS concentration in CYP3A4 IM/NMs and RMs were 16.9 ± 4.5 ng/mL and 14.2 ± 3.9 ng/mL, respectively (p=0.048). Carriers of the T allele for ABCB1 C2677T (2677 CT and 2677 TT) had a significantly higher mean tacrolimus SS concentration compared to non-carriers (17.5 ± 4.3 ng/mL vs. 14.6 ± 4.2 ng/mL, p=0.009). There was no significant difference in the mean tacrolimus SS concentration based on CYP3A5, ABCB1 C1236T and ABCB1 C3435T polymorphisms (p>0.05).Conclusion:ABCB1 C2677T and CYP3A4 appear to be important determinants of tacrolimus exposure after IV administration in adult patients receiving an allogeneic SCT. Our results did not demonstrate an association between CYP3A5 genotype and tacrolimus concentration, possibly due to IV administration and differential expression of CYP3A5 (higher in the gut resulting in first-pass metabolism). Further studies are necessary to validate these findings on a larger scale and to evaluate genotype-guided dose selection to optimize tacrolimus exposure. Future guidelines should discuss potential differences in pharmacogenetics findings between oral and IV tacrolimus and different populations (SCT vs. solid organ transplant). [Display omitted] DisclosuresTrivedi:Pharmacyclics: Consultancy, Honoraria. Grunwald:Alexion: Consultancy; Incyte: Consultancy, Research Funding; Celgene: Consultancy; ARIAD: Consultancy; Cardinal Health: Consultancy; Amgen: Consultancy, Research Funding; Pfizer: Consultancy; Forma Therapeutics: Research Funding; Janssen: Research Funding; Genentech: Research Funding. Ghosh:Seattle Genetics: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Jassen: Consultancy, Honoraria, Research Funding; Kite Pharma: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Low-Dose Plerixafor and Granulocyte Colony-Stimulating Factor for First-Line Autologous Peripheral Blood Stem Cell Mobilization in Lymphoma and Multiple Myeloma

Introduction: Approximately 10-30% of candidates to autologous hematopietic stem cell transplant (HSCT) are unable to collect an adequate yield of CD34+ cells/kg to support high-dose chemotherapy and autologous HSCT. Peripheral blood stem cell (PBSC) mobilization strategies vary considerably but the optimal methodology for mobilizing PBSC is not well defined. Plerixafor (Mozobil®) is approved for the mobilization of PBPC in combination with G-CSF at a dose of 0.24 mg/kg once daily for up to 4 consecutive days; however, it is an expensive drug and is expected to increase costs associated with PBSC harvest. Failure of peripheral blood (PB) mobilization and harvest is a critical issue for multiple myeloma (MM) and non hodgkin´s lymphoma (NHL) since the correlation between successful engraftment and the number of CD34+ cells infused is well established. We aim to investigate the safety and efficacy of the administration of low-dose plerixafor in mobilizing CD34+ cells plus G-CSF in MM and NHL.Methods: It is a preliminary report of a single-institution, open-label, phase II trial to test the feasibility and efficacy for mobilization of low-dose plerixafor added to daily G-CSF administration in adult patients with MM or NHL undergoing autologous HSCT. Institution ethic board approved the trial and all patients provided written informed consent. Consecutive patients in autologous transplant protocol with MM or NHL were included. The mobilization protocol consisted of G-CSF (10 μg/kg) subcutaneously daily for 4 days and plerixafor (0.12 mg/kg) administered subcutaneously 11 hours prior to initiation of apheresis. Stem cells collection was performed with a Cobe Spectra® or Spectra Optia® apheresis system. The planned target blood volume to be processed was 4-fold total blood volume calculated according to patients' weight and size. Peripheral blood CD34+ counts were analyzed using flow cytometry. Primary endpoint was the proportion of patients achieving at least 2 x 106 CD34+cells/kg in 1 apheresis harvest. Secondary end points included the rate of successful CD34+ cell mobilization, defined as a peak of CD34+ cells in PB >20 cells/mL. We measure PB CD34+ cells the day 4 and 5 after plerixafor administration. Toxicities and engraftment were documented.Results: Between april 2017 and july 2017, nine patients has been enrolled. Six with MM and 3 with NHL. The median PB CD34+ cell count for patients on day 4 before receiving plerixafor was 12.3/mL (range, 2.2-168.8) and 65.4/mL (range, 8.2-360.7) on day 5 after plerixafor (P=0.103). The median collection yield was 4.9 x 106 CD34+ cells/Kg (range, 1.4 - 24.5 million CD34+ cells/Kg). Plerixafor was well tolerated in most patients, only 2 referred moderate diarrhea. Eight of the 9 patients reached the target cell count (88.8%) with only 1 day of collection. Seven of nine patients had hematopoietic recovery with median neutrophil and platelet engraftment of 14 (range, 10-16) and 12 days (range, 10-16), respectively. Two patients are on day +1 and +5 and waiting for engraftment.Conclusions: Failure of PBSC mobilization is a critical issue for MM and NHL patients undergoing autologous HSCT. The combination of low-dose plerixafor with G- CSF in this study achieved 88% of successful yields, and appears to be an efficient and safe approach in first-line to improve the success of the yield. Aside of the costs related to plerixafor, this strategy can be counterweighed by reducing other resources as reducing number of apheresis and possibly reducing the impact on quality of life for patients. DisclosuresGomez-Almaguer:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol: Consultancy, Membership on an entity's Board of Directors or advisory committees.

CSF concentration of cefotaxime in adult patients with pneumococcal meningitis: a multicentre retrospective study.

Pneumococcal meningitis is a devastating disease that requires adequate meningeal antibiotic penetration to limit the mortality. Despite a large usage in this indication, data about CSF concentration of cefotaxime during pneumococcal meningitis in adults are scarce. Therefore, we aimed to describe the CSF concentration obtained after high-dose cefotaxime administration in adult patients treated for Streptococcus pneumoniae meningitis. In this multicentre, observational, retrospective study, cases of adult patients with S. pneumoniae meningitis hospitalized between January 2013 and October 2019 for whom cefotaxime concentration was measured in CSF were reviewed. Cefotaxime concentration was analysed in 44 CSF samples collected among 31 patients. Median (IQR) age was 61 years (52-69). Dexamethasone was administered in 27 subjects. Median (IQR) cefotaxime daily dosage was 15 g (12-19), corresponding to 200 mg/kg (150-280). CSF samples were collected approximately 5 days after cefotaxime initiation. Median (IQR, range) cefotaxime CSF concentration was 10.3 mg/L (4.8-19.3, 1.2-43.4). Median (range) MIC for Streptococcus pneumoniae was 0.25 mg/L (0.008-1) (n = 22). The median (IQR, range) CSF/MIC ratio was 38 (12-146, 4-1844). Twenty-five CSF concentrations (81%) were above 10 times the MIC. Cefotaxime was discontinued in two patients for toxicity. In-hospital mortality rate was 29%. Adult patients with pneumococcal meningitis treated with a high dose of cefotaxime (200 mg/kg/day) had elevated CSF concentrations with satisfying pharmacokinetics/pharmacodynamics parameters and tolerability profile. This study brings reassuring pharmacological data regarding the use of high-dose cefotaxime monotherapy for treating pneumococcal meningitis with susceptible strains to cefotaxime.

Reconstitution of IgG Subclasses Following Immunoglobulin Administration in Adult Patients with Common Variable Immune Deficiency

Background: Immunoglobulin (Ig) therapy reduces the frequency and severity of infection among patients with antibody deficiency disorders. However, a subset of patients lacks adequate clinical response. Objective: The purpose of this study was to determine in adult common variable immune deficiency (CVID) patients (A) if lack of clinical response to Ig therapy correlates with lack of reconstitution of IgG subclass (es), (B) correlation between Ig dosing and/or IgG trough levels and IgG subclass reconstitution, (C) and most common impaired Streptococcus pneumoniae (S. pneumoniae) serotype antibody response. Methods: Single-institution, retrospective chart review for CVID patients at immunology clinics from 2015 to 2019. Patients were monitored every 3–6 months for IgG dosage, IgG trough levels, IgG subclass reconstitution, infectious episodes (chronic sinusitis, bronchitis, upper respiratory, and lower respiratory tract infections), urinary tract infections, and antibiotic use. Follow-up was calculated in patient years. Results: Twenty-five of 41 patients achieved complete reconstitution of all IgG subclasses, and 16/41 demonstrated intermittent or lack of reconstitution. There were significantly less (p < 0.001) infections among fully reconstituted patients (0.66 ± 0.19 infections per patient year) as compared to those with intermittent or lack of reconstitution (1.26 ± 0.13 infections per patient year). There was a significant correlation between IgG trough levels and IgG subclass reconstitution. Most common impaired S. pneumoniae serotype included 3, 4, 9n, 10a, 11a, 12f, and 15b. Conclusions: Incomplete IgG subclass reconstitution was associated with increased frequency of infections. IgG trough levels correlate with IgG subclass reconstitution. A limited number of S. pneumoniae serotype antibodies are commonly impaired in CVID.

Introduction of self-injection increases compliance with dupilumab administration in adult patients with atopic dermatitis: A single-center retrospective study

To the Editor: Dupilumab has demonstrated good efficacy1 and effectiveness2,3 for adult patients with moderate to severe atopic dermatitis. However, it needs to be administered subcutaneously every 2 weeks. In Japan, self-injection of dupilumab has been available since May 2019. Without self-injection, patients need to visit physicians every 2 weeks; however, regular visits to a hospital or clinic are often hindered for various reasons. Self-injection at home can release patients from regular visits, which is expected to lead to higher compliance, but it has not been introduced in many clinics. In this study, we retrospectively investigated whether introduction of self-injection increases compliance to dupilumab administration.

Radiation dose reduction for CT-guided intrathecal nusinersen administration in adult patients with spinal muscular atrophy

Intrathecal administration of nusinersen in adult spinal muscular atrophy (SMA) patients with scoliosis and spondylodesis requires image guidance, which is preferably achieved with multi-detector computed tomography (MDCT). As long-term treatment is necessary and patients are young, radiation doses should be reduced to a minimum whilst a sufficient image quality for precise interventional performance should be kept. We compared 44 MDCT standard-dose scans (133.0–200.0 mA) with a hybrid iterative reconstruction (iDose4) to 20 low-dose scans (20.0–67.0 mA) with iterative model reconstruction (IMR), which were performed for procedure planning of intrathecal nusinersen administration in 13 adult patients with SMA and complex spinal conditions. Qualitative image evaluation, including confidence for intervention planning, was performed by two neuroradiologists for standard- and low-dose scans. All 64 MDCT-guided intrathecal administrations of nusinersen were successful. The dose length product (DLP) was significantly lower when using low-dose scanning with IMR (median DLP of standard-dose scans: 92.0 mGy•cm vs. low-dose scans: 34.5 mGy•cm; p < 0.0001). Image quality was significantly reduced for low-dose compared to standard-dose scanning. However, bone/soft tissue contrast and confidence for intervention planning were not significantly impaired in low-dose MDCT according to both readers, showing good inter-reader agreement. Thus, we hereby demonstrate a low-dose MDCT protocol combined with advanced image reconstruction for scanning during procedure planning as a viable option for image guidance in intrathecal nusinersen treatment of adult SMA patients with complex spinal conditions.

Phytosterolaemia associated with parenteral nutrition administration in adult patients.

Vegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) μg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) μg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (-6·21 (sd 4·73) μg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

GHRH plus arginine and arginine administration evokes the same ratio of GH isoforms levels in young patients with Prader-Willi syndrome

Human GH is present in pituitary and circulation as several isoforms, the prevalent being 22kDa- and 20kDa-GH. Recently, we have demonstrated the preservation of a normal balance in GH isoforms after GH releasing hormone (GHRH) plus arginine (ARG) administration in adult patients with Prader-Willi syndrome (PWS), one of the most common causes of syndromic obesity, often associated with GH deficiency (GHD). Aim of the present study was to measure circulating levels of 22kDa- and 20kDa-GH in young PWS patients (n=24; F/M: 10/14; genotype UPD/DEL/met+: 11/11/2; age: 10.8±5.3years; BMI SDS: 2.0±2.0; GHD: 16/24; obesity: 12/24) after combined GHRH+ARG or ARG administration. The results were analysed subdividing the GHRH+ARG and ARG groups on the basis of PWS genotype, GHD status and obesity. Circulating levels of 22kDa- and 20kDa-GH were measured by a chemiluminescent or fluorescent method based on specific pairs of monoclonal antibodies.GHRH+ARG or ARG significantly stimulated the secretion of 22kDa-GH but not that of 20kDa-GH in all PWS patients. No significant GHRH+ARG- vs. ARG-induced changes in the ratios of 22kDa- to 20kDa-GH peaks were observed in all PWS patients, although 22kDa- or 20kDa-GH peaks were significantly higher in the GHRH+ARG than ARG group. When subdividing PWS patients in UPD vs. DEL, obese vs. non obese and GHD vs. non GHD subgroups, GH peaks were significantly higher in nonobese than obese patients and in non GHD than GHD patients administered with either GHRH+ARG or ARG test, apart from the comparisons in the DEL/UPD subgroups. Anyway, the ratios of peak levels of 22kDa- to 20kDa-GH were similar after GHRH+ARG vs. ARG in all subgroups investigated.In conclusion, this study shows that administration of two different pharmacological tests, i.e. ARG, capable of reducing hypothalamic somatostatinergic tone, and GHRH (+ARG), that directly acts at pituitary level on the somatotropic cell, evokes the same ratios of GH isoforms in young PWS patients, suggesting that the hypothalamic dysfunction in this genetic disorder does not alter the qualitative and quantitative composition of GH isoforms present in circulation.

Reslizumab and Eosinophilic Asthma: One Step Closer to Precision Medicine?

Human eosinophils represent approximately 1% of peripheral blood leukocytes. However, these cells have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophilic inflammation is present in a significant proportion of patients with severe asthma. Asthma is a chronic inflammatory disorder that affects more than 315 million people worldwide, with 10% having severe uncontrolled disease. Although the majority of patients can be efficiently treated, severe asthmatics continue to be uncontrolled and are at risk of exacerbations and even death. Interleukin-5 (IL-5) plays a fundamental role in eosinophil differentiation, maturation, activation and inhibition of apoptosis. Therefore, targeting IL-5 is an appealing approach to the treatment of patients with severe eosinophilic asthma. Reslizumab, a humanized anti-IL-5 monoclonal antibody, binds with high affinity to amino acids 89–92 of IL-5 that are critical for binding to IL-5 receptor α. Two phase III studies have demonstrated that reslizumab administration in adult patients with severe asthma and eosinophilia (≥400 cells/μL) improved lung function, asthma control, and symptoms. Thus, the use of blood eosinophils as a baseline biomarker could help to select patients with severe uncontrolled asthma who are likely to achieve benefits in asthma control with reslizumab. In conclusion, targeted therapy with reslizumab represents one step closer to precision medicine in patients with severe eosinophilic asthma.

Emergency Department Pain Management in Adult Patients With Traumatic Injuries Before and After Implementation of a Nurse-Initiated Pain Treatment Protocol Utilizing Fentanyl for Severe Pain

BackgroundPain management in the emergency department (ED) remains suboptimal. Nursing staff protocols could improve this, but studies show divergent results. ObjectiveOur aim was to evaluate a nurse-initiated pain-management protocol in adult patients with traumatic injuries in the short and in the long term, utilizing fentanyl for severe pain. MethodsIn this pre–post implementation study, ED patients were included during three periods. The protocol allowed nurses to administer acetaminophen, non-steroidal anti-inflammatory drugs, or fentanyl autonomously, based on Numeric Rating Scale pain scores. Primary outcome was frequency of analgesic administration at 6 and 18 months after implementation. Secondary outcomes were pain awareness, occurrence of adverse events, and pain treatment after discharge. ResultsFive hundred and twelve patients before implementation were compared with 507 and 468 patients at 6 and 18 months after implementation, respectively. Analgesic administration increased significantly at 18 months (from 29% to 36%; p = 0.016), not at 6 months (33%; p = 0.19) after implementation. Pain awareness increased from 30% to 51% (p = 0.00) at 6 months and to 56% (p = 0.00) at 18 months, due to a significant increase in pain assessment: 3% to 30% (p = 0.00) and 32% (p = 0.00), respectively. Post-discharge pain treatment increased significantly at 18 months compared to baseline (from 25% to 33%; p = 0.016) and to 6 months (from 24% to 33%; p = 0.004). No adverse events were recorded. ConclusionsImplementation of a nurse-initiated pain-management protocol only increases analgesic administration in adult patients with traumatic injuries in the long term. Auditing might have promoted adherence. Pain awareness increases significantly in the short and the long term.

Approach to the Treatment of Diabetic Ketoacidosis

Diabetic ketoacidosis (DKA), a common cause of severe metabolic acidosis, remains a life-threatening condition due to complications of both the disease and its treatment. This Acid-Base and Electrolyte Teaching Case discusses DKA management, emphasizing complications of treatment. Because cerebral edema is the most common cause of mortality and morbidity, especially in children with DKA, we emphasize its pathophysiology and implications for therapy. The risk for cerebral edema may be minimized by avoiding a bolus of insulin, excessive saline resuscitation, and a decrease in effective plasma osmolality early in treatment. A goal of fluid therapy is to lower muscle venous Pco2 to ensure effective removal of hydrogen ions by bicarbonate buffer in muscle and diminish the binding of hydrogen ions to intracellular proteins in vital organs (such as the brain). In patients with DKA and a relatively low plasma potassium level, insulin administration may cause hypokalemia and cardiac arrhythmias. It is suggested in these cases to temporarily delay insulin administration and first administer potassium chloride intravenously to bring the plasma potassium level close to 4mmol/L. Sodium bicarbonate administration in adult patients should be individualized. We suggest it be considered in a subset of patients with moderately severe acidemia (pH<7.20 and plasma bicarbonate level< 12mmol/L) who are at risk for worsening acidemia, particularly if hemodynamically unstable. Sodium bicarbonate should not be administered to children with DKA, except if acidemia is very severe and hemodynamic instability is refractory to saline administration.

Variation in diurnal sedation in mechanically ventilated patients who are managed with a sedation protocol alone or a sedation protocol and daily interruption

BackgroundMechanically ventilated patients may receive more sedation during the night than during the day, potentially delaying extubation. We compared nighttime and daytime benzodiazepine and opioid administration in adult patients enrolled in a multicenter sedation trial comparing protocolized sedation alone or protocolized sedation combined with daily sedation interruption; and we evaluated whether nighttime and daytime doses were associated with liberation from mechanical ventilation.MethodsThis is a secondary analysis of a randomized trial which was conducted in 16 North American medical-surgical ICUs. In all 423 patients, nurses applied a validated sedation scale hourly to titrate benzodiazepine and opioid infusions to achieve a light level of sedation. Using fentanyl equivalents and midazolam equivalents, we compared dosages administered during night (19:00 to 07:00) and day (07:00 to 19:00) shifts. Using multivariable logistic regression we evaluated the association between nighttime and daytime opioid and sedative doses, and spontaneous breathing trial (SBT) conduct, SBT success, and extubation.ResultsNighttime benzodiazepine and opioid doses were significantly higher than daytime doses (mean difference midazolam equivalents 23.3 mg, 95 % CI 12.9, 33.8, p < 0.0001; mean difference fentanyl equivalents 356 mcg, 95 % CI 130, 582, p = 0.0021). Mean Sedation Agitation Scale score was similar between night and day, and was at target (3.2 vs 3.3, 95 % CI −0.05, 0.02, p = 0.35). Self-reported nurse workload was similar during the night and day. Patients were more often restrained during day shifts (76.3 % vs 73.7 %, p < 0.0001), and there were more unintentional device removals during the day compared with night (15.9 % vs 9.1 %, p < 0.0001). Increases in nighttime drug doses were independently associated with failure to meet SBT screening criteria, SBT failure, and the decision not to extubate the patient despite successful SBT.ConclusionPatients received higher doses of opioids and benzodiazepines at night. Higher nighttime doses were associated with SBT failure and delayed extubation.Trial registrationClinicalTrials.gov NCT00675363. Registered 7 May 2008.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1405-3) contains supplementary material, which is available to authorized users.

Time to First Antimicrobial Administration After Onset of Sepsis in Critically Ill Children

Delay of antimicrobial administration in adult patients with severe sepsis and septic shock has been associated with a decrease in survival to hospital discharge. The primary objective of this investigation was to determine the time to first antimicrobial administration after the onset of sepsis in critically ill children. Secondary objectives included appropriateness of empiric antimicrobials and microbiological testing, fluid resuscitation during the first 24 hours after onset of sepsis, intensive care unit and hospital length of stay, and mortality. Retrospective, chart review of all subjects less than or equal to 18 years of age admitted to the pediatric intensive care unit (PICU) with a diagnosis of sepsis between January 1, 2011, and December 31, 2012. A total of 72 subjects met the inclusion criteria during the study period. Median time to first antimicrobial administration by a nurse after the onset of sepsis was 2.7 (0.5-5.1) hours. Cultures were drawn prior to administration of antimicrobials in 91.7% of subjects and were repeated within 48 hours in 72.2% of subjects. Empiric antimicrobial regimens were appropriate in 91.7% of cases. The most common empiric antimicrobial regimens included piperacillin/tazobactam plus vancomycin in 19 subjects (26.4%) and ceftriaxone plus vancomycin in 15 subjects (20.8%). Median PICU length of stay was 129 (64.6-370.9) hours, approximately 5 days, and median hospital length of stay was 289 (162.5-597.1) hours, approximately 12 days. There were 4 deaths during the study period. Time to first antimicrobial administration after onset of sepsis was not optimal and exceeded the recommendations set forth in international guidelines. At our institution, the process for treating pediatric patients with severe sepsis and septic shock should be modified to increase compliance with national guidelines.