Predictors Of Days Research Articles

Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy

BackgroundDihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy.MethodsMalaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively.ResultsThe incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004).ConclusionLower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP.Trial registrationRegistered 09/12/2016, PACTR201612001901313.

Learning curve for intracorporeal robotic Padua ilealbladder: 10-year functional assessment from a high-volume single-centre series.

To assess the impact of the learning curve (LC) on perioperative and long-term functional outcomes of a consecutive single-centre series of robot-assisted radical cystectomy with Padua intracorporeal orthotopic neobladder. Patients treated between 2013 and 2022 were included, with ≥1 year of follow-up. The entire cohort was divided in tertiles. Categorical and continuous variables were compared. Joinpoint regression analysis was used to identify significant changes over the decade in linear slope of the 1-year day- and night-time continence. Uni- and multivariable Cox regression analyses identified predictors of day- and night-time continence recovery. Day-time continence was defined as 'totally dry' (no pads), night-time continence as pad wetness ≤50 mL (one safety pad). Overall, 200 patients were included. The mean hospital stay (P = 0.002) and 30-day complications (P = 0.04) significantly reduced over time; the LC significantly impacted on Trifecta achievement (P < 0.001). The 1-year day- and night-time continence probabilities displayed a significant improving trend (day-time continence annual average percentage change [AAPC] 11.45%, P < 0.001; night-time continence AAPC 10.05%, P = 0.009). The LC was an independent predictor of day- (hazard ratio [HR] 1.008; P < 0.001) and night-time continence (HR 1.004; P = 0.03) over time. Patients at the beginning of the LC had significantly longer hospitalisations, more postoperative complications, and lower Trifecta rates. At the 10-year analyses, we observed a significant improving trend for both the 1-year day- and night-time continence probabilities, highlighting the crucial role of the LC. However, we are unable to assess the case volume needed to achieve a plateau in terms of day- and night-time continence rates.

Do academic accommodations help students recover following sport-related concussion? A retrospective study of 96 youth athletes.

Many schools utilize academic accommodations to help athletes return-to-learn after sport-related concussion, yet little is known about the impact of accommodations on recovery. In a cohort of adolescent athletes with sport-related concussion, the authors sought to 1) describe academic accommodations, 2) determine predictors of receiving accommodations, and 3) determine how accommodations influenced recovery, as defined by days to return-to-learn, symptom resolution, and return-to-play. A retrospective survey study was undertaken that included all athletes between the ages of 12 and 24 years who were seen at a regional sport-related concussion center from April 1, 2020, to April 1, 2022. Demographic characteristics, past medical history, injury characteristics, school-related factors, and recovery were collected via a telephone-based survey and from medical charts. The independent variable was the use of academic accommodations by students. The outcome variables included days to return-to-learn, symptom resolution, and return-to-play. Univariable and multivariable logistic regression analyses were performed. Of 300 athletes contacted, 96 consented to participate in this study (mean age ± SD 16.6 ± 2.6 years, 60.4% male). The mean return-to-learn was 9.0 ± 13.2 days. In total, 63.5% of athletes received some kind of school accommodation. The most common accommodations included extra time on tests (46/96 [47.9%] athletes) and extra time for assignments (43/96 [44.8%]), whereas preferential seating in class (0/96 [0.0%]) and reduced workloads (4/96 [4.2%]) were the least commonly used accommodations. Multivariable logistic regression revealed that White race (OR 0.17, 95% CI 0.02-0.71, p = 0.03) and higher initial Post-Concussion Symptom Scale (PCSS) score (OR 1.04, 95% CI 1.01-1.07, p = 0.02) were predictive of receiving accommodations. Univariable models showed that receiving accommodations was not predictive of return-to-learn (β = 4.67, 95% CI -0.92 to 10.25, p = 0.10), symptom resolution (β = 24.71, 95% CI -17.41 to 66.83, p = 0.26), or return-to-play (β = 13.35, 95% CI -14.56 to 41.27, p = 0.35). Regarding other predictors of each outcome, several factors emerged irrespective of accommodations. Multivariable analysis revealed that longer time to return-to-learn was associated with a history of psychiatric illness (β = 8.00, 95% CI 1.71-14.29, p = 0.02) and initial PCSS score (β = 0.14, 95% CI 0.06-0.23, p < 0.01). Finally, predictors of days to return-to-play included school personnel who were knowledgeable of concussion (β = -5.07, 95% CI -9.93 to -0.21, p = 0.04) and higher initial PCSS score (β = 0.67, 95% CI 0.04-1.29, p = 0.03). The most common accommodation was extra time on tests/assignments, whereas reduced workload was the least common. White race and greater initial PCSS score were associated with receiving accommodations. Receiving accommodations did not significantly impact days to return-to-learn, symptom resolution, or return-to-play.

Identifying predictors of Day 5 blastocyst utilization rate using an artificial neural network

Can artificial intelligence identify predictors of an increased Day 5 blastocyst utilization rate (D5BUR), which is one of the most informative key performance indicators in an IVF laboratory? This retrospective, multicentre study evaluated six variables for predicting D5BUR using an artificial neural network (ANN): number of metaphase II (MII) oocytes injected (intracytoplasmic sperm injection); use of autologous/donated gametes; maternal age at oocyte retrieval; sperm concentration; progressive sperm motility rate; and fertilization rate. Cycles were divided into training and testing sets through stratified random sampling. D5BUR on Day 5 was grouped into <60% and ≥60% as per the Vienna consensus benchmark values. The area under the receiver operating characteristic curve (AUC) to predict the D5BUR groups was 80.2%. From the ANN model, all six independent variables were found to be of significant value for the prediction of D5BUR (P<0.0001), with the most important variable being the number of MII oocytes injected. Investigation of the effect of MII oocytes injected on D5BUR indicated an inverse correlation, with injection of an increasing number of MII oocytes resulting in a decreasing D5BUR (r=-0.344, P<0.001) and injection of up to six oocytes resulting in D5BUR ≥60%. The number of MII oocytes injected is the most important predictor of D5BUR. Exploration of additional variables and further validation of models that can predict D5BUR can guide the way towards personalized treatment and increased safety.

P-176 Morphokinetic Expressions Predict Day Five Embryo Quality and Implantation - A Prospective Observational Study

Abstract Study question The aim of this prospective study was to investigate the value of human embryo morphokinetics as predictors of day 5 embryo quality and implantation. Summary answer Day 5 embryo quality was predicted best by Cleavage Synchronicity 2-8-cell stage (CS2-8). Implantation was predicted best by the time to the expanded blastocyst (tEB-tPNf). What is known already Time-lapse imaging technology enables embryologists to observe and assess not only embryo morphology but also kinetics and cleavage synchronicity. It was found that time intervals like time from 5- to 8-cell stage (s3 = t8 - t5) can predict blastocyst formation. Cetinkaya et al. defined four relative morphokinetic expressions describing cleavage synchronicity: Cleavage Synchronicity 2-8-, 4-8-, 2-4-cell stage (CS2-8, CS4-8, CS2-4) and DNA Replication time ratio (DR). In a retrospective study they found that CS2-8 followed by s3, and CS4-8 were better predictors of blastocyst quality than absolute cleavage time points (https://doi.org/10.1007/s10815-014-0341-x). Study design, size, duration This prospective observational study was conducted between December 2020 and October 2021 at a single university hospital. Patients between 18 and 45 years who underwent stimulated IVF or ICSI treatment with embryo culture in a time-lapse incubator were included. Exclusion criteria were endometriosis, PCOS, history of chemotherapy, PGT cycles and end of culture before day 5. Every patient was included only once (n = 100). Implantation was assessed for all patients with embryo transfer. Participants/materials, setting, methods Embryos (n = 298) reaching at least 8-cell stage were annotated for morphokinetics and divided into four groups based on day 5 morphology: top (TQ; n = 60), good (GQ; n = 69), poor quality (PQ; n = 105) or not reaching blastocyst stage (AE; n = 64). Absolute times were normalized to fading of pronuclei (tPNf). ROC-analysis was performed to test how morphokinetics predict quality and implantation (only known-implantation-data; n = 110). Main results and the role of chance To predict day 5 embryo quality, four morphokinetic expressions had an Area Under the Curve (AUC) of more than 0.7, including CS2-8 (AUC = 0.732), CS4-8 (AUC = 0.717), s3 (AUC = 0.724) and the start of blastulation (tSB-tPNf) (AUC = 0.725). All morphokinetic expressions mentioned were significantly different between TQ plus GQ versus PQ plus AE embryos (p &amp;lt; 0.001). Additionally, the data of each morphokinetic parameter were divided into four quarters using the 25th, 50th and 75th percentile. CS2-8 had a rate of 67.6% TQ plus GQ blastocysts in the fourth quarter (CS2-8 &amp;gt; 0.86). CS4-8, s3 and tSB-tPNf had the highest rate of TQ plus GQ blastocysts (64.3 %, 64.3 %, 72.9 %) in the first quarter (CS4-8≤0.20, s3≤3.01 h, tSB-tPNf ≤ 67.06 h). Implantation was predicted best by the time to reach the morula stage (tM-tPNf; AUC = 0.636, p = 0.049), start blastulation (tSB-tPNf; AUC = 0.660, p = 0.022) and expanded blastocyst (tEB-tPNf; AUC = 0.688, p = 0.009). The relative expressions CS2-8 and CS4-8 and the interval s3 were not significantly different between implanted and non-implanted embryos. Limitations, reasons for caution Morphokinetic annotation is open to inter- and intraobserver variability, although partially controlled by prospectivity. The ROC-analysis does not adjust for statistical dependence between embryos of one patient. The used morphological groups do not necessarily measure developmental potential. Embryos with KID showed less morphokinetic variation because of pre-selection for transfer. Wider implications of the findings The findings could contribute to an early decision model on transfer hierarchy that would help avoiding costs and a potential negative influence of prolonged blastocyst culture. Observing the kinetics of blastocyst formation (tM, tSB, tEB) might allow an improved prediction of implantation potential. Trial registration number DRKS00022983

Plasma neurofilament light chain protein as a predictor of days in delirium and deep sedation, mortality and length of stay in critically ill patients.

SummaryBackgroundDelirium predicts poor outcomes, however identifying patients with the worst outcomes is challenging. Plasma neurofilament light protein (NfL) is a sensitive indicator of neuronal damage. We undertook an exploratory observational study to determine the association between plasma NfL and delirium in the critically ill.MethodsMoDUS was a randomised placebo-controlled delirium trial of simvastatin done in an UK adult general ICU. We measured NfL levels in plasma samples using a Single molecule array (Simoa) platform. We explored associations between patient's plasma NfL levels and number of delirium days, and clinical outcomes. The control group for baseline NfL were preoperative patients undergoing major surgery.FindingsThe majority of critically ill patients already had a high NfL level on admission. Patients with higher plasma NfL levels at days one and three spent more days in delirium or deep sedation. Patients with zero or one day in delirium or deep sedation had day one mean concentrations of 37.8 pg/ml (SD 32.6) compared with 96.5 pg/ml (SD 106.1)) for patients with two days or more, p-value 0.002 linear mixed effects model.Survivors discharged before 14 days had lower mean plasma NfL concentrations compared to those with longer hospital stays and/or who died within six months. The area under ROC curve for predicting death within six months using day one NfL was 0.81 (0.7,0.9).InterpretationMeasurement of plasma NfL within three days of admission may be useful to identify those patients with worse clinical outcomes, and as an enrichment strategy for future delirium interventional trials in the critically ill.FundingAlzheimer's Society UK, UK Dementia Research Institute.

Semi-quantitative magnetic resonance imaging scoring of the knee detects previous injuries in professional soccer players

PurposeThe medical examination (“medical”) is an important procedure in professional soccer since it has high economic relevance. In addition to clinical tests, magnetic resonance imaging (MRI) is used to assess joint health. In the present study, the reliability of semiquantitative knee MRI during the “medical” in professional soccer was tested, and its relationship with clinical data and days missed due to knee injury was observed.MethodsIn this cross-sectional study, between 2012 and 2019, 69 newly assigned players (age 18–35 years) from a professional soccer club underwent MRI (3.0 T) of both knee joints during their “medical”. Reported knee injuries and previously missed days due to injury were obtained from player anamnesis and the “transfermarkt.com” database. Based on the established “Whole-Organ Magnetic Resonance Imaging Score” (WORMS), two independent radiologists graded the MRI results. Further evaluation was based on the mean score of both knees.ResultsThe mean WORMS for all subjects was 13.9 (median 10.5, range 0–61). Players with previous injuries had significantly higher scores than players without reported injuries (22.1 ± 17.7 vs. 8.9 ± 4.4, p < 0.002). Three outliers (previously undetected injuries) in the group of players without reported injuries were observed (6.7%). The WORMS was significantly correlated with a prior knee injury (r: 0.424, p < 0.0001) and days missed due to injury (r: 0.489, p < 0.001). Age was correlated with the WORMS (r: 0.386, p < 0.001). In a linear regression model, prior injury was the only significant predictor of a high WORMS (p = 0.001). The WORMS was a significant predictor of days missed due to injury (p < 0.0002) and prior injury (sensitivity: 78%, specificity: 91%, p = 0.006). The intraclass correlation coefficient was excellent (0.89).ConclusionSemiquantitative knee MRI for WORMS determination during the soccer “medical” is a robust and reliable method. Prior injury, even in players without documented trauma, was detected by the WORMS, and previously missed days due to injury were correlated with the semiquantitative MR knee score.Level of evidenceLevel III.

Characterizing social and policy determinants of hospital length of stay among paediatric inpatients with diabetes using linked population-based data.

BackgroundEvidence is limited on the non-medical factors influencing hospital length of stay (LOS) among paediatric inpatients with diabetes, notably potential social and policy correlates. This study aimed to characterize the associations of socioeconomic status and health policy environment with diabetes-attributable LOS to help inform accountability monitoring of a provincial comprehensive diabetes strategy aiming to minimize time in hospital among this high-risk population.Data and methodsThis retrospective population-based study drew on multiple linked administrative and geospatial databases among all children aged 18 and under with a diabetes-related hospitalization in the province of New Brunswick, Canada, during the four-year period following implementation of an insulin pump funding program. Multiple linear regression was used to assess the role of access to the public insulin pump resourcing scheme and relative neighbourhood deprivation as predictors of days spent in acute care, controlling for age, sex, and place of residence.ResultsAmong the paediatric inpatient population (N = 386), 21% had accessed social resources made available through the insulin pump funding policy and 42% resided in the most materially deprived neighbourhoods. Diabetes-related hospital stays averaged 3.87 days. Paediatric inpatients having accessed resources through the social insurance policy spent significantly fewer days in hospital (1.34 days less [95% CI: 0.63–2.05]) than those who had not, all else being equal. Observed differences in LOS by neighbourhood socioeconomic deprivation were not found to be statistically significant in the multivariate analysis.ConclusionFindings from this context of universal medical coverage suggested that public policy for supplemental financing of assistive technologies among children with diabetes may be associated with reduced burden to the hospital system. The causes of socioenvironmental disparities in LOS require further investigation to inform interventions to mitigate preventable patient-level variations in hospital-based health outcomes.

99. Immune Responses to Influenza Vaccines in Children and Young Adults

BackgroundImmune responses to influenza vaccines (IV) are influenced by pre-existing antibodies to vaccine components. Immune responses to vaccines were evaluated following vaccination with quadrivalent egg-based live-attenuated influenza vaccine (LAIV4) and cell-culture inactivated influenza vaccine (ccIIV4).MethodsRacially diverse (48.0% non-white), healthy, community-dwelling children and young adults aged 4-21 years (median, 18.3 years) were randomized 1:1 in blocks of 4 to receive intramuscular ccIIV4 (Flucelvax: n=100) or nasal LAIV4 (FluMist: n=98); baseline demographics were similar between groups. Blood was drawn at day 0 pre-vaccination and at day 28 (21-35 days) post vaccination. Hemagglutination inhibition (HI) assays against egg-grown A/H1N1, A/H3N2, both vaccine B/strains and cell-grown A/H3N2 antigens were conducted. Geometric mean titers (GMT) and geometric mean fold rise (GMFR) in titers were analyzed. ResultsDay 0 GMTs were similar for LAIV4 and ccIIV4. Day 28 GMTs were higher for ccIIV4 (p< 0.05) and increased following vaccination for all 5 antigens (p< 0.05) except B/Phuket following LAIV4. The GMFR range was 2.4 to 3.0 for ccIIV4 and 1.0 to 1.3 for LAIV4. In linear regression controlling for age and prior season vaccination for both vaccines, baseline titers inversely predicted GMFR. The GMFR to A/H3N2 cell-grown and egg-grown antigens were similar within vaccine type.Figure 1. Day 0 and Day 28 A(H1N1) titers for ccIIV4Figure 2. Day 0 and Day 28 A(H1N1) titers for LAIV4ConclusionThe HI response to ccIIV4 was greater than LAIV4 in this study of mostly older children. Day 0 HI titers were 1) a significant determinant of GMFR; 2) the strongest predictors of day 28 GMFR; and 3) more highly correlated (negatively) with GMFR following ccIIV4 than LAIV4. For both IV, the GMFR for cell-grown and egg-grown A/H3N2 antigens did not differ within IV type. Future studies incorporating immunoglobulin and cellular immune responses may delineate differences between these IV types not observable through HI assays. Disclosures Mary Patricia Nowalk, PhD, Merck & Co., Inc. (Grant/Research Support) Richard K. Zimmerman, MA;MD;MPH;MS, Sanofi Pasteur (Research Grant or Support) Judith M. Martin, MD, Merck Sharp and Dohme (Consultant)

FACTORS AFFECTING EMBRYO DEVELOPMENTAL PACE

Ovarian follicle size reportedly correlates with oocyte maturity and embryo morphology. The day of blastulation (day 5, 6, or 7) has been correlated with embryo implantation potential. The objective of this study was to identify factors, including follicle diameter, that might influence the day of embryo blastulation. In this prospective observational study, patients underwent routine ovarian stimulation with exogenous gonadotropins. Each aspirated follicle was sonographically measured during oocyte collection. Embryos were cultured to the blastocyst stage. The day of blastulation was recorded for blastocysts of transferable quality (no CC grades). Blastocysts forming after day 5 were considered delayed. Logistic regressions were run to determine if patient age, follicle diameter, and the total number of eggs collected correlated with blastocyst formation on day 5. Because of the potential for biopsy to artificially influence blastulation, separate logistic regression models were developed for biopsied and non-biopsied blastocysts. P<0.05 was considered significant. The day of blastulation was recorded for 514 blastocysts derived from measured follicles, 221 of which formed on day 5, 249 on day 6, and 44 on day 7. Two logistic regression models were constructed. The first logistic model was developed predicting day 5 blastulation among the 170 biopsied blastocysts. The only significant predictor of day 5 blastulation in this model was follicle diameter (P=0.0038). The second logistic model was developed for 344 blastocysts that were not biopsied. In this second model, the only significant predictor of day 5 blastulation was, again, follicle diameter (P=0.0067). In both models, increasing follicle diameter corresponded with increased risk of delayed blastulation (day 6 or day 7 blastulation). Regardless of biopsy for PGT-A, larger follicles were significantly associated with delayed blastulation. Patient age and the number of eggs collected were not significant predictors of delayed blastulation.

Predictors of working days lost due to sickness absence and disability pension

ObjectiveTo identify social and health-related predictors of the number of days lost due to sickness absence (SA) and disability pension (DP) among initially 55-year-old public-sector workers.MethodsThe data from the Finnish Helsinki Health Study included participants aged 55 years at the baseline (in 2000–2002, N = 1630, 81% women), and were enriched with register-based information on SA and DP. The cumulative number of calendar days lost due to SA ≥ 1 day or DP between ages 55 and 65 was calculated. Negative binomial regression model was used to identify the predictors of days lost.ResultsThe average calendar days lost was 316 days (about 220 working days) during a 10-year follow-up, and 44% were due to SA and 56% due to DP. Smoking [incidence rate ratio (IRR) = 1.19, 95% CI 1.01–1.40 for past and IRR = 1.30, CI 1.07–1.58 for current], binge drinking (IRR = 1.22, CI 1.02–1.46), lifting or pulling/pushing heavy loads (IRR = 1.35, CI 1.10–1.65), awkward working positions (IRR = 1.24, CI 1.01–1.53), long-standing illness limiting work or daily activities (IRR = 2.32, CI 1.93–2.79), common mental disorder (IRR = 1.52, CI 1.30–1.79), and multisite pain (IRR = 1.50, CI 1.23–1.84) increased the number of days lost, while high level of education (IRR = 0.66, CI 0.52–0.82) and moderate level of leisure-time physical activity (IRR = 0.80, CI 0.67–0.94) reduced the number of days lost.ConclusionsModifiable lifestyle risk factors, workload factors, common mental disorder, and multisite pain substantially increase the number of days lost. However, the findings of this study could be generalized to female workers in the public sector. Future research should also consider shorter SA spells in estimating working years lost and working life expectancy.

Predictors of Cytopenia after Treatment with Axicabtagene Ciloleucel in Patients with Large Cell Lymphoma

Predictors of Cytopenia after Treatment with Axicabtagene Ciloleucel in Patients with Large Cell Lymphoma

A-144 Mild Traumatic Brain Injury and Sleep Disturbances in Military Service Members as Predictors of Days Missed from Duty

Abstract Objective Duty-limiting pain impacts military readiness. Conditions such as mild traumatic brain injury (mTBI), stress-related disorders (Acute Stress Disorder (ASD)/PTSD), depression, anxiety and sleep disturbance occur frequently among military service members and can be associated with pain-related time off from duty. The purpose of this study was to explore which of these conditions best predict time off duty. Method Time off duty was categorized into low (0–3 days), medium (3–30 days) and high (more than 30 days). After excluding participants undergoing a Medical Evaluation Board (MEB) or with potentially invalid symptom reporting, 364 military service members were included. An ordinal regression analysis was conducted with presence or absence of mTBI, ASD/PTSD, depression/anxiety and sleep disturbance as predictors. Results The regression model was significant (χ2 = 21.93, p &amp;lt; .001), with mTBI status and sleep disturbance emerging as significant predictors of pain-related time off duty. Those with a history of mTBI were five times more likely to miss duty days than those without mTBI (Odds Ratio (OR) = 5.09 [p = .04]). Presence of ongoing sleep disturbance conveyed two times the risk of more missed duty (OR = 2.09 [p = .04]). Conclusion This suggests that treating mTBI and sleep disturbances in military service members can reduce pain-related absenteeism and consequently improve military readiness.

Diffuse optical spectroscopic imaging reveals distinct early breast tumor hemodynamic responses to metronomic and maximum tolerated dose regimens

BackgroundBreast cancer patients with early-stage disease are increasingly administered neoadjuvant chemotherapy (NAC) to downstage their tumors prior to surgery. In this setting, approximately 31% of patients fail to respond to therapy. This demonstrates the need for techniques capable of providing personalized feedback about treatment response at the earliest stages of therapy to identify patients likely to benefit from changing treatment. Diffuse optical spectroscopic imaging (DOSI) has emerged as a promising functional imaging technique for NAC monitoring. DOSI uses non-ionizing near-infrared light to provide non-invasive measures of absolute concentrations of tissue chromophores such as oxyhemoglobin. In 2011, we reported a new DOSI prognostic marker, oxyhemoglobin flare: a transient increase in oxyhemoglobin capable of discriminating NAC responders within the first day of treatment. In this follow-up study, DOSI was used to confirm the presence of the flare as well as to investigate whether DOSI markers of NAC response are regimen dependent.MethodsThis dual-center study examined 54 breast tumors receiving NAC measured with DOSI before therapy and the first week following chemotherapy administration. Patients were treated with either a standard of care maximum tolerated dose (MTD) regimen or an investigational metronomic (MET) regimen. Changes in tumor chromophores were tracked throughout the first week and compared to pathologic response and treatment regimen at specific days utilizing generalized estimating equations (GEE).ResultsWithin patients receiving MTD therapy, the oxyhemoglobin flare was confirmed as a prognostic DOSI marker for response appearing as soon as day 1 with post hoc GEE analysis demonstrating a difference of 48.77% between responders and non-responders (p < 0.0001). Flare was not observed in patients receiving MET therapy. Within all responding patients, the specific treatment was a significant predictor of day 1 changes in oxyhemoglobin, showing a difference of 39.45% (p = 0.0010) between patients receiving MTD and MET regimens.ConclusionsDOSI optical biomarkers are differentially sensitive to MTD and MET regimens at early timepoints suggesting the specific treatment regimen should be considered in future DOSI studies. Additionally, DOSI may help to identify regimen-specific responses in a more personalized manner, potentially providing critical feedback necessary to implement adaptive changes to the treatment strategy.

Arch intervention following stage 1 palliation in hypoplastic left heart syndrome is associated with slower feed advancement: a report from the National Pediatric Quality Cardiology Improvement Collaborative.

Infants undergoing stage 1 palliation for hypoplastic left heart syndrome may have post-operative feeding difficulties. Although the cause of feeding difficulties in these patients is multi-factorial, residual arch obstruction may affect gut perfusion, contributing to feeding intolerance. We hypothesised that undergoing arch reintervention following stage 1 palliation would be associated with post-operative feeding difficulties. This was a retrospective cohort study. We analysed data from the National Pediatric Cardiology Quality Improvement Collaborative, which maintains a multicentre registry for infants with hypoplastic left heart syndrome discharged home following stage 1 palliation. Patients who underwent arch reintervention (percutaneous or surgical) prior to discharge following stage 1 palliation were compared with those who underwent non-aortic arch interventions after stage 1 palliation and those who underwent no intervention. Median post-operative days to full enteral feeds and weight for age z-scores were compared. Predictors of post-operative days to full feeds were identified. Among patients who underwent arch reintervention, post-operative days to full enteral feeds were greater than for those who underwent non-aortic arch interventions (25 versus 16, p = 0.003) or no intervention (median days 25 versus 12, p < 0.001). Arch intervention, multiple interventions, gestational age, and the presence of a gastrointestinal anomaly were predictors of days to full feeds. Repeat arch intervention is associated with a longer time to achieve full enteral feeding in patients with hypoplastic left heart syndrome after stage 1 palliation. Further investigation of this association is needed to understand the role of arch obstruction in feeding problems in these patients.

Validation of the simplified modified Rankin scale for stroke trials: Experience from the ENCHANTED alteplase-dose arm.

The structured, simplified modified Rankin scale questionnaire (smRSq) may increase reliability over the interrogative approach to scoring the modified Rankin scale (mRS) in acute stroke research and practice. During the conduct of the alteplase-dose arm of the international ENhanced Control of Hypertension ANd Thrombolysis StrokE stuDy (ENCHANTED), we had an opportunity to compare each of these approaches to outcome measurement. Baseline demographic data were recorded together with the National Institutes of Health Stroke Scale (NIHSS). Follow-up measures obtained at 90 days included mRS, smRSq, and the 5-Dimension European Quality of life scale (EQ-5D). Agreements between smRSq and mRS were assessed with the Kappa statistic. Multiple logistic regression was used to identify baseline predictors of Day 90 smRSq and mRS scores. Treatment effects, based on Day 90 smRSq/mRS scores, were tested in logistic and ordinal logistic regression models. SmRSq and mRS scores had good agreement (weighted Kappa 0.79, 95% confidence interval (CI) 0.78-0.81), while variables of age, atrial fibrillation, diabetes mellitus, pre-morbid mRS (1 vs. 0), baseline NIHSS scores, and imaging signs of cerebral ischemia, similarly predicted their scores. Odds ratios for death or disability, and ordinal shift, 90-day mRS scores using smRSq were 1.05 (95% CI 0.91-1.20; one-sided P = 0.23 for non-inferiority) and 0.98 (95% CI 0.87-1.11; P = 0.02 for non-inferiority), similar to those using mRS. This study demonstrates the utility of the smRSq in a large, ethnically diverse clinical trial population. Scoring of the smRSq shows adequate agreement with the standard mRS, thus confirming it is a reliable, valid, and useful alternative measure of functional status after acute ischemic stroke. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.

Outcomes and Predictors of Response in Steroid-Refractory Acute Graft-versus-Host Disease.

The prognosis of steroid-refractory acute graft-versus-host disease (aGVHD) is poor, and predictors of response and survival are unclear. In an exploratory analysis of 203 steroid-refractory aGVHD patients with prospectively collected GVHD data who received antithymocyte globulin, etanercept, or mycophenolate mofetil (MMF) as second-line treatment, we determined the predictors of day 28 response, 2-year overall survival, and 2-year nonrelapse mortality (NRM). To minimize the risk of finding false-positive results, we used least absolute shrinkage and selection operator regression, aggressively eliminating variables that are unlikely to be associated with outcome. Day 28 response to second-line therapy was 38% (complete response, 23%), with a 2-year overall survival of 25% and a 2-year NRM of 62%. Factors associated with response were GVHD prophylaxis, organ involvement, and initial aGVHD to steroid-refractory aGVHD interval. Specifically, compared with cyclosporine/MMF as GVHD prophylaxis, the odds ratio (OR) for calcineurin inhibitor/methotrexate was .8 and for cyclosporine/prednisone .6. The OR for aGVHD to steroid-refractory aGVHD interval ≥ 14 versus <14 days was 1.3. The ORs for skin only involvement and gut or liver only involvement when compared with multiorgan involvement were 1.4 and 1.2, respectively. The only variable associated with worse survival was age, with a hazard ratio (HR) per decade of 1.04 for overall mortality. Similarly, age was the only variable associated with NRM (HR per decade, 1.02). When compared with complete response, no response at day 28 increased the risk of death (HR, 2.4; 95% confidence interval, 1.5 to 3.7). In conclusion, by means of an underused statistical technique in the field of transplantation, we identified predictors of response and survival in steroid-refractory aGVHD. Our results highlight the importance of developing novel treatment strategies because current treatments yield poor outcomes.

Diarrhea, Dehydration, and the Associated Mortality in Children with Complicated Severe Acute Malnutrition: A Prospective Cohort Study in Uganda

To assess predictors of diarrhea and dehydration and to investigate the role of diarrhea in mortality among children with complicated severe acute malnutrition. A prospective cohort study, nested in a probiotic trial, was conducted in children with complicated severe acute malnutrition. Children were treated according to World Health Organization and national guidelines, and diarrhea and dehydration were assessed daily. Multiple linear and log-linear Poisson regression models were used to identify predictors of days with diarrhea and dehydration, respectively, and multiple logistic regression was used to assess their role in mortality. Among 400 children enrolled, the median (IQR) age was 15.0months (11.2-19.2months), 58% were boys, and 61% had caregiver-reported diarrhea at admission. During hospitalization, the median (range) number of days with diarrhea was 5 (0-31), the median duration of hospitalization was 17days (1-69days), and 39 (10%) died. Of 592 diarrhea episodes monitored, 237 were admission episodes and 355 were hospital acquired. During hospitalization, young age was associated with days with diarrhea, and young age and HIV infection were associated with dehydration. Both days with diarrhea and dehydration predicted duration of hospitalization as well as mortality. The odds of mortality increased by a factor of 1.4 (95% CI, 1.2-1.6) per day of diarrhea and 3.5(95% CI, 2.2-6.0) per unit increase in dehydration score. Diarrhea is a strong predictor of mortality among children with complicated severe acute malnutrition. Improved management of diarrhea and prevention of hospital-acquired diarrhea may be critical to decreasing mortality.

Days at Home in the Last 6 Months of Life: A Patient-Determined Quality Indicator for Cancer Care.

Quality end-of-life care (EoLC) is a key aspect of oncology. Days at home in the last 6 months of life represents a novel, patient-driven quality indicator of EoLC. We measured days at home in a large population of patients with cancer in Ontario, Canada. Trends over time and predictors of more or less time at home were also determined. We conducted a population-based retrospective study using health administrative data linked by unique, encoded identifiers and analyzed at the ICES. Quantile regression was used to determine significant predictors of more or less time at home. Of 72,987 patients who died of cancer in Ontario, Canada and met our inclusion criteria, the median number of days spent at home in the last 6 months of life was 164 (interquartile range [IQR], 144 to 175 days) of a possible 180 days. Patients with hematologic cancers spent significantly fewer days at home (156; IQR, 134 to 170 days). The strongest predictors of more time at home were male sex (+2.87 days relative to female sex; CI, 2.43 to 3.31 days) and receipt of palliative care before the last 6 months of life (+2.38 days; CI, 1.95 to 2.08 days). Additional predictors included income, age, cancer type, comorbidity burden, and health region. The majority of patients (69.7%) did not die at home. Days at home in the last 6 months of life, obtained from administrative data, can be used as a measure of quality EoLC. Predictors of days at home may prove valuable targets for future policy intervention.

INCREASING VALUE: CAN MIDSHAFT CLAVICLE FRACTURES BE SURGICALLY TREATED AS AN OUTPATIENT?

Purpose In the US, ambulatory surgical centers (ASCs) are an increasingly popular approach to lowering costs by managing patients in an outpatient setting. There is also a trend towards operative management of clavicle fractures, one of the most commonly fractured bones in children. Here, we evaluate the safety and success of open reduction and internal fixation (ORIF) of the clavicle, still an understudied procedure in the pediatric population. Furthermore, we appraise the feasibility of performing clavicle ORIF at ASCs, with an eye toward improving the value of an increasingly commonplace operation. Methods We reviewed the records of 82 consecutive pediatric patients who underwent clavicle ORIF from 2011 to 2015. 6 patients had proximal third fractures and were excluded. Data from the remaining 76 patients were analyzed. Patients discharged the day of surgery were defined as feasible for ASC management. Other factors relevant to the feasibility of ASC management were examined including: length of admission, surgical admission directly from the emergency department (ED), complications, patient controlled analgesia (PCA) use, and recovery. Results The 76 patients had a mean age of 15.3 ± 2.0 years. 29 (38.2%) were discharged the day of surgery, and 73 (96.1%) were discharged after one night or less. 13 (17.1%) patients received PCA. 21 (27.6%) patients were admitted for surgery directly from the ED. 17 (22.4%) experienced postoperative complications, including anesthesia/parasthesia near the operative site, constipation, 5 cases of hardware problems, and 1 nonunion. In 54 patients for whom active range of motion was described at final follow-up (mean time to follow-up 17.0 ± 12.0 weeks), 49 (90.7%) regained full range of motion, including all 40 patients followed 8 or more weeks postoperatively. 2 patients successfully underwent ORIF at an ASC without incident. Univariate analysis revealed that PCA use (p=0.024) was positively correlated with day of surgery discharge. Both univariate (p=0.025) and multivariate analysis (p=0.019) revealed a negative correlation between admission directly from the ED and day of surgery discharge. Conclusion Given the lack of serious complications, and the strong clinical outcomes seen in our large patient group, our data suggest that clavicle fixation is a safe and effective procedure in the pediatric population. Furthermore, over a third of patients were discharged the same day, suggesting that a significant proportion of our patients could have been managed in an ASC. Importantly, ED admission is a strong negative predictor of day of surgery discharge, and thus feasibility for ASC management. The increasingly operative management of clavicle fractures, a common injury, constitutes a unique opportunity to improve value. Future studies should explore how delays in surgical treatment, analgesic regimens like PCA, and other factors may affect length of postoperative stay, which in turn may further define a subpopulation well-suited for ASC management.