Timing of Pegfilgrastim: Association with Febrile Neutropenia in a Pediatric Solid and CNS Tumor Population

2021 ◽  
Vol 38 (6) ◽  
pp. 375-384
Author(s):  
Laura Schlenker ◽  
Renee C.B. Manworren

Background: While recommended timing of pegfilgrastim administration is ≥24 h after chemotherapy, patient barriers to next day administration, available adult evidence, and pharmacokinetic data have led to earlier administration in some pediatric patients with solid and central nervous system tumors. The purpose of this study was to compare patient outcomes by timing of pegfilgrastim after chemotherapy. Methods: A retrospective chart review examined timing of 932 pegfilgrastim administrations to 182 patients, 0–29 years of age. The primary outcome was febrile neutropenia (FN); the secondary outcome was neutropenic delays (ND) ≥7 days to next chemotherapy cycle. To account for multiple pegfilgrastim administrations per patient, a generalized mixed model was used with a logit link for the dichotomous outcomes (FN & ND), timing as the dichotomous independent variable, and random effect for patient. Results: FN occurred in 196 of 916 cycles (21.4%); and ND in 19 of 805 cycles (2.4%). The fixed effect of pegfilgrastim administration < or ≥24 h after chemotherapy was not significant, p = .50; however, earlier or later than 20 h was significant, p = .005. FN odds were significantly higher when pegfilgrastim was given <20 h (OR 1.78, 95% CI: 1.19–2.65) after chemotherapy, which may be attributable to differences in chemotherapy toxicity regardless of pegfilgrastim timing. Discussion: While attempts should be made to administer pegfilgrastim ≥24 h after chemotherapy, if barriers exist, modified timing based on individual patient characteristics should be considered. Prospective randomized trials are needed to identify lower risk patients for early pegfilgrastim administration.

Author(s):  
Alice Iannaccone ◽  
Andrea Fusco ◽  
Antanas Skarbalius ◽  
Audinga Kniubaite ◽  
Cristina Cortis ◽  
...  

Purpose: Assessing the relationship between external load (EL) and internal load (IL) in youth male beach handball players. Methods: A total of 11 field players from the Lithuanian U17 beach handball team were monitored across 14 training sessions and 7 matches. The following EL variables were assessed by means of inertial movement units: PlayerLoad™, accelerations, decelerations, changes of direction, and jumps and total of inertial movements. IL was assessed objectively and subjectively using the summated heart rate zones and training load calculated via session rating of perceived exertion, respectively. Spearman correlations (ρ) were used to assess the relationship between EL and IL. The interindividual variability was investigated using linear mixed models with random intercepts with IL as dependent variable, PlayerLoad™ as the independent variable, and players as random effect. Results: The lowest significant (P < .05) relationship was for high jumps with objective (ρ = .56) and subjective (ρ = .49) IL. The strongest relationship was for PlayerLoad™ with objective (ρ = .9) and subjective (ρ = .84) IL. From the linear mixed model, the estimated SD of the random intercepts was 19.78 arbitrary units (95% confidence interval, 11.75–33.31); SE = 5.26, and R2 = .47 for the objective IL and 6.03 arbitrary units (95% confidence interval, 0.00–7330.6); SE = 21.87; and R2 = .71 for the subjective IL. Conclusions: Objective and subjective IL measures can be used as a monitoring tool when EL monitoring is not possible. Coaches can predict IL based on a given EL by using the equations proposed in this study.


BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e037557
Author(s):  
Mary Halter ◽  
Vari Drennan ◽  
Chao Wang ◽  
Carly Wheeler ◽  
Heather Gage ◽  
...  

ObjectivesTo compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training.DesignMixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates.SettingThree emergency departments in England.ParticipantsThe records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation.Primary and secondary outcome measuresThe primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience.ResultsRe-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p<0.001), after adjustment for patient characteristics, triage severity of condition and statistically significant clinician intraclass correlation. Clinical reviewers found almost all patients’ charts clinically adequate. Physician associates were evaluated as assessing patients in a similar way to foundation year two doctors-in-training and providing continuity in the team. Patients were positive about the care they had received from a physician associate, but had poor understanding of the role.ConclusionsPhysician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies.


2019 ◽  
Vol 97 (11) ◽  
pp. 4482-4487
Author(s):  
J Daniel Rivera ◽  
Amelia R Woolums ◽  
Steeve Giguère ◽  
Joseph T Johnson ◽  
Alexis G Lutz ◽  
...  

Abstract Remote delivery devices (RDD) are used by some to administer antimicrobials (AM) to cattle when treatment by manual injection is logistically difficult. However, it is not clear that the pharmacokinetics (PK) of AM administered by RDD is comparable to that for AM administered by injection; thus, it is not certain that cattle treated by RDD experience equivalent AM effect. Fifteen crossbred beef steers (body weight [BW] = 302.5 ± 21.7 kg) were used in a three-way crossover study to determine the PK of tulathromycin following administration with RDD in the BQA injection triangle. Cattle were treated by each of three methods at 2.5 mg of tulathromycin per kg of BW with a 60 d washout period between treatments: 1) subcutaneous injection of tulathromycin (SC), 2) treatment by RDD delivered by air pump projector (AIR, Pneudart, Model 178B) at 4.5 m distance, and 3) treatment by RDD delivered by CO2-powered projector at 7.5 m (CO2, Pneudart, Model 176B). Blood was collected prior to injection and at various points up to 552 h post-administration, pharmacokinetic data were analyzed as a mixed model using animal as a random effect and method of administration, order of administration, and their interaction as fixed effects. Plasma creatine kinase (CK) was measured before treatment and at 24 h after treatment to determine the degree of muscle injury resulting from each treatment. Three darts administered by AIR did not discharge (20%; 95% CI = 4% to 48%); and results from these steers were excluded from analysis. Maximum plasma concentration (718, 702.6, and 755.5 µg/mL for SC, AIR, and CO2, respectively) and area under the concentration-time curve (17,885, 17,423, and 18,796 µg • h/mL for SC, AIR and CO, respectively) were similar and not significantly different between methods of administration. There was an effect of time (P = 0.0002), period (P = 0.0001), and interaction between method of administration and study period (P = 0.0210) on plasma concentration of CK. However, method of treatment (P = 0.6091), interaction between method and time (P = 0.6972), interaction between period and time (P = 0.6153), and 3-way interaction between method, period and time (P = 0.6804) were not different. Results suggest that PK of tulathromycin following delivery by RDD can be similar to subcutaneous injection; however, failure of RDD to discharge after delivery by some types of projectors can cause an important proportion of cattle to fail to receive drug as expected.


2014 ◽  
Vol 32 (31_suppl) ◽  
pp. 43-43
Author(s):  
Michelle Farnan ◽  
Erica Smeltz ◽  
Susan Glod ◽  
Nancy Parson ◽  
Margaret Kreher

43 Background: Early integration of specialty Palliative Care (PC) in cancer patients improves quality of life and lowers medical costs. Engaging cancer patients early remains challenging. A checklist approach that evaluates type of malignancy, comorbidities, functional status, uncontrolled symptoms, readmission rates, and psychosocial/spiritual distress may prompt consultation to the PC team. We evaluated a palliative care screening tool’s (PCST) effect on promoting early PC consultation for oncology inpatients. Methods: A modified version of the Center to Advance Palliative Care screening tool was utilized by our hospital as part of the admission assessment. Registered nurses completed the PCST within 24 hours of admission for all adults. A PCST score of 3 or higher prompted staff to suggest a PC consult. A retrospective chart review of oncology patients who received a PC consult was performed to assess whether the screening tool score within 24 hours of admission impacted timing of a consult order. Effective tool utilization was considered to be a consult order within 36 hours of a high risk screen score. Results: From January through March 2014, 215 cancer patients screened with the PCST were found to have a score of 3 or higher. Seventy seven percent scored a 3 or higher, and PC consultation occurred in 16% of that patient cohort. Twenty three percent of PC consults occurred in patients scoring less than 3. The average number of days from admission to PC consult was 6 days. Conclusions: Using a PCST did not trigger PC consultation for inpatient cancer patients. Thirty four percent of the screened patients died during that admission, indicating a dramatic change in status from admission or ineffective prognostication, both barriers to early integration of PC. Our work suggests that a screening tool alone, even in a center with a well-embedded PC program, is not a sufficient means of effectively integrating PC into a patient’s hospital stay. Further work to identify patient characteristics that lead to consultation in both high and low risk patients is necessary.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S829-S830
Author(s):  
Elwyn W Welch ◽  
Shaila Sheth ◽  
Chester Ashong ◽  
Caroline Pham

Abstract Background Nitrofurantoin has been used to treat cystitis in women; however, data supporting its use in men is lacking. In addition, recent retrospective studies have challenged the manufacturer’s recommendation to avoid nitrofurantoin with creatinine clearances (CrCl) less than 60 mL/min. The purpose of this study is to compare the efficacy and safety of nitrofurantoin for the treatment of acute cystitis in male and female veterans with variable degrees of renal dysfunction. Methods A retrospective chart review was conducted in adult patients who received nitrofurantoin for acute cystitis in the outpatient setting between May 1, 2018 and May 1, 2019. The primary outcomes were rates of clinical cure as compared between males and females, and across various renal function groups (CrCl greater than 60 mL/min, 30 to 60 mL/min, and less than 30 mL/min) following treatment with nitrofurantoin. The secondary outcome was adverse event rates. Results A total of 446 patients were included with 278 females and 168 males. Overall clinical cure rate was 86.5% (n=386). Clinical cure rate did not vary between genders (p=0.0851) or CrCl ranges (p=1.0) as shown in the tables. Benign prostatic hyperplasia (BPH) was associated with decreased odds of clinical cure (OR 0.50 [95% CI 0.26-0.97], p=0.0404) in addition to cirrhosis (OR 0.22 [95% CI 0.06-0.91], p=0.0357). Adverse events occurred in 2% of patients and did not vary based on gender or renal function. RATES OF CLINICAL CURE Conclusion There was no statistically significant difference in clinical cure with nitrofurantoin between genders and various renal impairments. However, history of BPH and cirrhosis were associated with decreased efficacy. Subgroup analysis also revealed lower efficacy in males with CrCl greater than 60 mL/min versus females with similar renal function. This study adds to the growing body of literature suggesting that renal dysfunction with CrCl of 30 to 60 mL/min may not carry the risk of treatment failure and adverse effects previously associated with nitrofurantoin, but large randomized trials are needed to confirm these results. Disclosures All Authors: No reported disclosures


2020 ◽  
pp. 1-37
Author(s):  
Tal Yarkoni

Abstract Most theories and hypotheses in psychology are verbal in nature, yet their evaluation overwhelmingly relies on inferential statistical procedures. The validity of the move from qualitative to quantitative analysis depends on the verbal and statistical expressions of a hypothesis being closely aligned—that is, that the two must refer to roughly the same set of hypothetical observations. Here I argue that many applications of statistical inference in psychology fail to meet this basic condition. Focusing on the most widely used class of model in psychology—the linear mixed model—I explore the consequences of failing to statistically operationalize verbal hypotheses in a way that respects researchers' actual generalization intentions. I demonstrate that whereas the "random effect" formalism is used pervasively in psychology to model inter-subject variability, few researchers accord the same treatment to other variables they clearly intend to generalize over (e.g., stimuli, tasks, or research sites). The under-specification of random effects imposes far stronger constraints on the generalizability of results than most researchers appreciate. Ignoring these constraints can dramatically inflate false positive rates, and often leads researchers to draw sweeping verbal generalizations that lack a meaningful connection to the statistical quantities they are putatively based on. I argue that failure to take the alignment between verbal and statistical expressions seriously lies at the heart of many of psychology's ongoing problems (e.g., the replication crisis), and conclude with a discussion of several potential avenues for improvement.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S254-S254
Author(s):  
Victoria Bengualid ◽  
Maria Martinez ◽  
Zhenisa Hysenaj ◽  
Debra M Willner ◽  
Judith Berger

Abstract Background The first case of COVID-19 was admitted on March 15th 2020 to our community based hospital in the Bronx, NY. The aim of this study is to describe the clinical characteristics and outcome of these first COVID-19 patients. Patient Characteristics and Outcome Methods IRB approved retrospective chart review study of all COVID-19 patients admitted during March 2020 focusing on patient characteristics, co-morbidities, clinical manifestations and outcome. Results A total of 177 patients were admitted during March 2020: 57% African American 23.1% Hispanic and 16.9% White. 44.9% female, average age 60 years, and 90% had at least one comorbidity. Outcome was available on all patients except for one who was transferred to another institution for ECMO. Overall mortality was 33%. Clinical presentation: 69.4% presented with cough or shortness of breath, 15.8% with diarrhea, nausea, vomiting or abdominal pain, and 14.6% with myalgia, dizziness or altered mental status. 6.2% presented only with fever. However 59.8% of patients presented with fever and respiratory or gastrointestinal symptoms. Mortality The table compares patients who died vs discharged (either home or to a short term facility). Those that were 65 years or older, hypertensive or presented to the ER with an oxygen saturation of 94% or lower, were more likely to die. Ventilated patients: 31.6% of patients were intubated with a mortality rate of 77%. 22% of these patients were intubated in the first 24 hours. Compared to non-intubated patients, there was no difference in BMI, diabetes, hypertension, COPD/Asthma, use of statins, aspirin or calcium channel blockers. Intubated patients older than 64 years had significantly higher mortality rates (p=0.0001). Conclusion This cohort of COVID-19 patients is unique as almost all received Hydroxychloroquine and Azithromycin. Only 9% received steroids and even fewer received an interleukin-6 inhibitor, convalescent plasma or Remdesivir. African Americans and Hispanics accounted for 80% of patients. Greater than 90% received Medicaid. Overall mortality was 33%. The most common presentation was respiratory followed by gastrointestinal symptoms. The overall mortality was 33% but increased to 77% in intubated patients. Age, hypertension, and ER oxygen saturation correlated with mortality. Disclosures All Authors: No reported disclosures


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 211-212
Author(s):  
Jerad Jaborek ◽  
Francis L Fluharty ◽  
Alejandro E Relling

Abstract The fatty acid (FA) composition of the longissimus muscle (LM) of Angus and Wagyu sired cattle raised to a similar body weight (612 kg) were compared at the 6th and 12th rib locations. Angus sired steers represented T1, cattle from a Wagyu sire selected for growth represented T2, and cattle from a Wagyu sire selected for marbling represented T3. Data were analyzed mixed model with repeated measurements on animal (LM location); the model include the fixed effect of treatment, LM location, and their interaction, and random effect of sex. The percentage of 16:0, 18:1cis9, 18:3, and monounsaturated FA (MUFA) exhibited a treatment*LM location interaction (P ≤ 0.7), where T2 cattle had a greater percentage of 16:0 and a lesser percentage of 18:1cis9, 18:3, and MUFA at the 12th rib vs. 6th rib location compared with T1 and T3 cattle. The percentage of total FA lipid, polyunsaturated FA(PUFA), and PUFA:SFA ratio in the LM were greater (P ≤ 0.02) for T3 cattle compared with T1 and T2 cattle. The percentage of 18:0 was greater (P ≤ 0.01) for T1 cattle compared with T2 and T3 cattle, while T1 cattle had a greater (P ≤ 0.01) percentage of saturated FA (SFA) compared to T3 cattle. The percentage of 18:1cis9, other 18:1cis isomers, 18:2, MUFA, and MUFA:SFA ratio were greater (P ≤ 0.02) for T3 cattle compared with T1 cattle, with T2 cattle being intermediate. The percentage of total FA lipid, 18:0, 18:1 trans isomers, and SFA were greater (P ≤ 0.01) at the 6th rib LM location, while 14:1, 18:cis9, other 18:1 cis isomers, MUFA, MUFA:SFA, and PUFA:SFA ratio were greater (P ≤ 0.02) at the 12th rib LM location


2020 ◽  
pp. 1471082X2096691
Author(s):  
Amani Almohaimeed ◽  
Jochen Einbeck

Random effect models have been popularly used as a mainstream statistical technique over several decades; and the same can be said for response transformation models such as the Box–Cox transformation. The latter aims at ensuring that the assumptions of normality and of homoscedasticity of the response distribution are fulfilled, which are essential conditions for inference based on a linear model or a linear mixed model. However, methodology for response transformation and simultaneous inclusion of random effects has been developed and implemented only scarcely, and is so far restricted to Gaussian random effects. We develop such methodology, thereby not requiring parametric assumptions on the distribution of the random effects. This is achieved by extending the ‘Nonparametric Maximum Likelihood’ towards a ‘Nonparametric profile maximum likelihood’ technique, allowing to deal with overdispersion as well as two-level data scenarios.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S807-S807
Author(s):  
John Raymond U Go ◽  
Cristina G Corsini Campioli ◽  
Omar Abu Saleh ◽  
John Wilson ◽  
Sharon Deml ◽  
...  

Abstract Background Mycobacterium septicum is a rapidly growing non-tuberculous mycobacterium. It is a ubiquitous organism capable of causing infections in both healthy and immunocompromised individuals. Only a few cases have been reported to date, and standard therapeutic regimens, and optimal treatment duration have not been defined. Methods We conducted a retrospective chart review of all patients seen at Mayo Clinic in Rochester, MN from July 2014 to March 2020 from whom Mycobacterium septicum was isolated in culture by our clinical microbiology laboratory. Results There were 12 patients identified with M. septicum infection – 7 males and 5 females. The average age was 67 years, with an age range of 48 to 80 years. Seven of 12 isolates obtained were from sputum samples. Only one patient was on immunosuppressive medication. Three cases were considered clinically significant infections for which directed anti-mycobacterial therapy was instituted. In two of these three cases, co-infection with Mycobacterium avium complex (MAC) was seen. Underlying structural lung disease was present in the two cases of pulmonary infections. Peritoneal dialysis catheter-related peritonitis was seen in the third case. All the isolates were susceptible to amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and trimethoprim-sulfamethoxazole (TMP-SMX). The isolates were resistant to clarithromycin and doxycycline. Patient Characteristics, Associated M. septicum Illness, and Therapy Provided Antimicrobial Susceptibility Profiles of the Mycobacterium septicum Isolates, MIC (mcg/mL) and Interpretation Patient Demographics and Specimen Source of Mycobacerium septicum Isolates Conclusion M. septicum is an unusual cause of non-tuberculous mycobacterial infection. The presence of a foreign body may increase the risk of infection. Individuals with underlying structural lung disease are also likely to be at increased risk of developing pulmonary infection. Generalized treatment recommendations are limited by the lack of prospective controlled trials; hence, optimal antibiotic regimen and treatment duration have not been firmly established. Susceptibility testing should be performed to guide treatment selection, but the use of combination therapy with potentially empiric agents like amikacin, ciprofloxacin, imipenem, linezolid, moxifloxacin, and TMP-SMX as demonstrated in this small study, can be considered. A high rate of macrolide resistance was noted in our study. Disclosures All Authors: No reported disclosures


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