Improving Pneumococcal Vaccination Rates in Immunosuppressed Pediatric Patients with Rheumatic Disease.

Background: Patients with rheumatic diseases are at a high risk of invasive pneumococcal disease due to immunosuppression. We conducted a quality improvement project, and the first aim was to increase the percentage of patients with systemic lupus erythematosus and mixed connective tissue disease that is up to date on pneumococcal vaccinations from 9.6% to 80% within one year. Subsequently, the second aim was to increase the percentage of patients on immunosuppression with systemic lupus erythematosus, mixed connective tissue disease, juvenile dermatomyositis and systemic vasculitis that is up to date on pneumococcal vaccinations from 62.6% to 80% within one year. Methods: Two process measures were up-to-date vaccination status on (1) 13-valent pneumococcal conjugated vaccine (PCV13) and (2) 23-valent pneumococcal polysaccharide vaccine (PPSV23). Our outcome measure was being fully up to date on both pneumococcal vaccinations. Interventions included an immunization algorithm, reporting of eligible patients, education, reminders, and pre-visit planning. Results: There were shifts in the centerline for all quality measures in both phases of this project. The combined pneumococcal vaccination rate for Phase 1 increased from 9.6% to 91.1%, and this centerline was sustained. Pneumococcal vaccination rates also significantly increased for Phase 2: 68.8% to 93.4% for PCV13, 65.2% to 88.5% for PPSV23, and 62.6% to 86.5% for the combined pneumococcal vaccination rate. Conclusions: Quality improvement methodology significantly increased and sustained pneumococcal vaccination rates in our high-risk, immunosuppressed patients. We continue to prioritize this important initiative to mitigate the risk of invasive pneumococcal disease.

Cardiorespiratory Responses to Acute Intermittent Hypoxia in Humans With Chronic Spinal Cord Injury.

Brief exposure to repeated episodes of low inspired oxygen, or acute intermittent hypoxia (AIH), is a promising therapeutic modality to improve motor function after chronic, incomplete spinal cord injury (SCI). Although therapeutic AIH is under extensive investigation in persons with SCI, limited data are available concerning cardiorespiratory responses during and after AIH exposure despite implications for AIH safety and tolerability. Thus, we recorded immediate (during treatment) and enduring (up to 30 min post-treatment) cardiorespiratory responses to AIH in 19 participants with chronic SCI (>1 year post-injury; injury levels C1 to T6; American Spinal Injury Association Impairment Scale A to D; mean age = 33.8 ± 14.1 years; 18 males). Participants completed a single AIH (15, 60-sec episodes, inspired O2 ≈ 10%; 90-sec intervals breathing room air) and Sham (inspired O2 ≈ 21%) treatment, in random order. During hypoxic episodes: (1) arterial oxyhemoglobin saturation decreased to 82.1 ± 2.9% (p < 0.001); (2) minute ventilation increased 3.83 ± 2.29 L/min (p = 0.008); and (3) heart rate increased 4.77 ± 6.82 bpm (p = 0.010). Considerable variability in cardiorespiratory responses was found among subjects; some individuals exhibited large hypoxic ventilatory responses (≥0.20 L/min/%, n = 11), whereas others responded minimally (<0.20 L/min/%, n = 8). Apneas occurred frequently during AIH and/or Sham protocols in multiple participants. All participants completed AIH treatment without difficulty. No significant changes in ventilation, heart rate, or arterial blood pressure were found 30 min post-AIH p > 0.05). In conclusion, therapeutic AIH is well tolerated, elicits variable chemoreflex activation, and does not cause persistent changes in cardiorespiratory control/function 30 min post-treatment in persons with chronic SCI.

Visuospatial cognition predicts performance on an obstructed vision obstacle walking task in older adults.

Walking performance and cognitive function demonstrate strong associations in older adults, with both declining with advancing age. Walking requires the use of cognitive resources, particularly in complex environments like stepping over obstacles. A commonly implemented approach for measuring the cognitive control of walking is a dual-task walking assessment, in which walking is combined with a second task. However, dual-task assessments have shortcomings, including issues with scaling the task difficulty and controlling for task prioritization. Here we present a new assessment designed to be less susceptible to these shortcomings while still challenging cognitive control of walking: the Obstructed Vision Obstacle (OBVIO) task. During the task, participants hold a lightweight tray at waist level obstructing their view of upcoming foam blocks, which are intermittently spaced along a 10 m walkway. This forces the participants to use cognitive resources (e.g., attention and working memory) to remember the exact placement of upcoming obstacles to facilitate successful crossing. The results demonstrate that adding the obstructed vision board significantly slowed walking speed by an average of 0.26 m/s and increased the number of obstacle strikes by 8-fold in healthy older adults (n = 74). Additionally, OBVIO walking performance (a score based on both speed and number of obstacle strikes) significantly correlated with computer-based assessments of visuospatial working memory, attention, and verbal working memory. These results provide initial support that the OBVIO task is a feasible walking test that demands cognitive resources. This study lays the groundwork for using the OBVIO task in future assessment and intervention studies.

Smart Start - Designing Powerful Clinical Trials Using Pilot Study Data.

Using Pilot Study Data to Design Clinical TrialsDigital health interventions are often studied in a pilot trial before full evaluation in a randomized controlled trial. The authors introduce Smart Start, a framework for using pilot study data to optimize the intervention and design the subsequent randomized controlled trial to maximize the chance of success.

Improving Arterial Puncture Success in Neonatal Patients Using Transillumination.

BACKGROUND: Arterial punctures are a common procedure used to obtain blood samples for lab tests that guide treatment of neonatal patients. These punctures can be painful and have associated risks, emphasizing the importance of keeping attempts to a minimum. PURPOSE: The purpose of this quality improvement initiative was to determine whether using transillumination to visualize arteries before and while obtaining a blood sample would improve outcomes in neonatal patients. METHODS: Quantitative data were collected pre- and postimplementation of education for the use of a transillumination device for arterial punctures on neonates in a level III neonatal intensive care unit (NICU). Outcomes followed included the success rate, average time to obtain a blood sample, and the average number of sticks to obtain a blood sample. Data were collected on 47 blood draw attempts in the control group (preimplementation) and 19 blood draw attempts in the experimental group (postimplementation). RESULTS: A statistical analysis concluded that the use of the studied transillumination device does positively affect the incidence of successful blood draws, particularly for the novice NICU nurse. In addition, the average number of sticks to obtain a blood sample significantly decreased in the experimental group. Finally, the average time to obtain a blood sample using the device was not impacted in this study. IMPLICATIONS FOR PRACTICE AND RESEARCH: Use of a transillumination device does appear to result in improved outcomes for arterial punctures in neonatal patients. More research is needed to confirm these findings due to the small sample size of the study.

Sympathetic nervous system responses during complex walking tasks and community ambulation post-stroke.

Stroke survivors frequently report increased perceived challenge of walking (PCW) in complex environments, restricting their daily ambulation. PCW is conventionally measured through subjective questionnaires or, more recently, through objective quantification of sympathetic nervous system activity during walking tasks. However, how these measurements of PCW reflect daily walking activity post-stroke is unknown. We aimed to compare the subjective and objective assessments of PCW in predicting home and community ambulation. In 29 participants post-stroke, we measured PCW subjectively with the Activities-specific Balance Confidence (ABC) Scale and objectively through electrodermal activity, quantified by change in skin conductance levels (SCL) and skin conductance responses (SCR) between outdoor-complex and indoor-steady-state walking. High-PCW participants were categorized into high-change SCL (ΔSCL ≥ 1.7 µs), high-change SCR (ΔSCR ≥ 0.2 µs) and low ABC (ABC < 72%) groups, while low-PCW participants were categorized into low-change SCL (ΔSCL < 1.7 µs), low-change SCR (ΔSCR < 0.2 µs) and high-ABC (ABC ≥ 72%) groups. Number and location of daily steps were quantified with accelerometry and Global Positioning System devices. Compared to low-change SCL group, the high-change SCL group took fewer steps in home and community (p = 0.04). Neither ABC nor SCR groups differed in home or community steps/day. Objective measurement of PCW via electrodermal sensing more accurately represents home and community ambulation compared to the subjective questionnaire.

The evolving role of data & safety monitoring boards for real-world clinical trials.

Introduction: Clinical trials provide the "gold standard" evidence for advancing the practice of medicine, even as they evolve to integrate real-world data sources. Modern clinical trials are increasingly incorporating real-world data sources - data not intended for research and often collected in free-living contexts. We refer to trials that incorporate real-world data sources as real-world trials. Such trials may have the potential to enhance the generalizability of findings, facilitate pragmatic study designs, and evaluate real-world effectiveness. However, key differences in the design, conduct, and implementation of real-world vs traditional trials have ramifications in data management that can threaten their desired rigor. Methods: Three examples of real-world trials that leverage different types of data sources - wearables, medical devices, and electronic health records are described. Key insights applicable to all three trials in their relationship to Data and Safety Monitoring Boards (DSMBs) are derived. Results: Insight and recommendations are given on four topic areas: A. Charge of the DSMB; B. Composition of the DSMB; C. Pre-launch Activities; and D. Post-launch Activities. We recommend stronger and additional focus on data integrity. Conclusions: Clinical trials can benefit from incorporating real-world data sources, potentially increasing the generalizability of findings and overall trial scale and efficiency. The data, however, present a level of informatic complexity that relies heavily on a robust data science infrastructure. The nature of monitoring the data and safety must evolve to adapt to new trial scenarios to protect the rigor of clinical trials.

APOE4, Age, and Sex Regulate Respiratory Plasticity Elicited by Acute Intermittent Hypercapnic-Hypoxia.

Rationale: Acute intermittent hypoxia (AIH) shows promise for enhancing motor recovery in chronic spinal cord injuries and neurodegenerative diseases. However, human trials of AIH have reported significant variability in individual responses. Objectives: Identify individual factors (eg, genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). Methods: In 17 healthy individuals (age = 27 ± 5 yr), associations between individual factors and changes in the magnitude of AIHH (15, 1-min O2 = 9.5%, CO2 = 5% episodes) induced changes in diaphragm motor-evoked potential (MEP) amplitude and inspiratory mouth occlusion pressures (P0.1) were evaluated. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity (BDNF, HTR2A, TPH2, MAOA, NTRK2) and neuronal plasticity (apolipoprotein E, APOE) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized (h)ApoE knock-in rats were performed to test causality. Results: AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE4 (i.e., APOE3/4) compared to individuals with other APOE genotypes (P = 0.048) and the other tested SNPs. Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (P = 0.004). Additionally, age was inversely related with change in P0.1 (P = 0.007). In hApoE4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE3 controls (P < 0.05). Conclusions: APOE4 genotype, sex, and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults. Addition to Knowledge Base: AIH is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative disease. Figure 5 Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, AIHH, in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.

Interventions to prevent miscarriage.

The physical and psychological impact of miscarriage can be devastating. There are many lifestyle and therapeutic interventions that may prevent a miscarriage. In this review, we have outlined the key areas for health optimization to prevent pregnancy loss, drawing on the most up-to-date evidence available. The 3 key areas identified are lifestyle optimization in women, lifestyle optimization in men, and therapeutic interventions. The evidence demonstrates that the treatments to consider are first-trimester progesterone administration, levothyroxine in women with subclinical hypothyroidism, and the combination of aspirin and heparin in women with antiphospholipid antibodies.

The influence of backward versus forward locomotor training on gait speed and balance control post-stroke: Recovery or compensation?

Backward walking training has been reported to improve gait speed and balance post-stroke. However, it is not known if gains are achieved through recovery of the paretic limb or compensations from the nonparetic limb. The purpose of this study was to compare the influence of backward locomotor training (BLT) versus forward locomotor training (FLT) on gait speed and dynamic balance control, and to quantify the underlying mechanisms used to achieve any gains. Eighteen participants post chronic stroke were randomly assigned to receive 18 sessions of either FLT (n = 8) or BLT (n = 10). Pre- and post-intervention outcomes included gait speed (10-meter Walk Test) and forward propulsion (time integral of anterior-posterior ground-reaction-forces during late stance for each limb). Dynamic balance control was assessed using clinical (Functional Gait Assessment) and biomechanical (peak-to-peak range of whole-body angular-momentum in the frontal plane) measures. Balance confidence was assessed using the Activities-Specific Balance Confidence scale. While gait speed and balance confidence improved significantly within the BLT group, these improvements were associated with an increased nonparetic limb propulsion generation, suggesting use of compensatory mechanisms. Although there were no improvements in gait speed within the FLT group, paretic limb propulsion generation significantly improved post-FLT, suggesting recovery of the paretic limb. Neither training group improved in dynamic balance control, implying the need of balance specific training along with locomotor training to improve balance control post-stroke. Despite the within-group differences, there were no significant differences between the FLT and BLT groups in the achieved gains in any of the outcomes.

A pharmacokinetic model of antiseizure medication load to guide care in the epilepsy monitoring unit.

OBJECTIVE: Evaluating patients with drug-resistant epilepsy often requires inducing seizures by tapering antiseizure medications (ASMs) in the epilepsy monitoring unit (EMU). The relationship between ASM taper strategy, seizure timing, and severity remains unclear. In this study, we developed and validated a pharmacokinetic model of total ASM load and tested its association with seizure occurrence and severity in the EMU. METHODS: We studied 80 patients who underwent intracranial electroencephalographic recording for epilepsy surgery planning. We developed a first order pharmacokinetic model of the ASMs administered in the EMU to generate a continuous metric of overall ASM load. We then related modeled ASM load to seizure likelihood and severity. We determined the association between the rate of ASM load reduction, the length of hospital stay, and the probability of having a severe seizure. Finally, we used modeled ASM load to predict oncoming seizures. RESULTS: Seizures occurred in the bottom 50th percentile of sampled ASM loads across the cohort (p < .0001, Wilcoxon signed-rank test), and seizures requiring rescue therapy occurred at lower ASM loads than seizures that did not require rescue therapy (logistic regression mixed effects model, odds ratio = .27, p = .01). Greater ASM decrease early in the EMU was not associated with an increased likelihood of having a severe seizure, nor with a shorter length of stay. SIGNIFICANCE: A pharmacokinetic model can accurately estimate ASM levels for patients in the EMU. Lower modeled ASM levels are associated with increased seizure likelihood and seizure severity. We show that ASM load, rather than ASM taper speed, is associated with severe seizures. ASM modeling has the potential to help optimize taper strategy to minimize severe seizures while maximizing diagnostic yield.

Recovery of walking in nonambulatory children with chronic spinal cord injuries: Case series.

The immature central nervous system is recognized as having substantial neuroplastic capacity. In this study, we explored the hypothesis that rehabilitation can exploit that potential and elicit reciprocal walking in nonambulatory children with chronic, severe (i.e., lower extremity motor score < 10/50) spinal cord injuries (SCIs). Seven male subjects (3-12 years of age) who were at least 1-year post-SCI and incapable of discrete leg movements believed to be required for walking, enrolled in activity-based locomotor training (ABLT; clinicaltrials.gov NCT00488280). Six children completed the study. Following a minimum of 49 sessions of ABLT, three of the six children achieved walking with reverse rolling walkers. Stepping development, however, was not accompanied by improvement in discrete leg movements as underscored by the persistence of synergistic movements and little change in lower extremity motor scores. Interestingly, acoustic startle responses exhibited by the three responding children suggested preserved reticulospinal inputs to circuitry below the level of injury capable of mediating leg movements. On the other hand, no indication of corticospinal integrity was obtained with transcranial magnetic stimulation evoked responses in the same individuals. These findings suggest some children who are not predicted to improve motor and locomotor function may have a reserve of adaptive plasticity that can emerge in response to rehabilitative strategies such as ABLT. Further studies are warranted to determine whether a critical need exists to re-examine rehabilitation approaches for pediatric SCI with poor prognosis for any ambulatory recovery.

APOE4, Age & Sex Regulate Respiratory Plasticity Elicited By Acute Intermittent Hypercapnic-Hypoxia.

Rationale: Acute intermittent hypoxia (AIH) is a promising strategy to induce functional motor recovery following chronic spinal cord injuries and neurodegenerative diseases. Although significant results are obtained, human AIH trials report considerable inter-individual response variability. Objectives: Identify individual factors ( e.g. , genetics, age, and sex) that determine response magnitude of healthy adults to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH). Methods: Associations of individual factors with the magnitude of AIHH (15, 1-min O 2 =9.5%, CO 2 =5% episodes) induced changes in diaphragm motor-evoked potential amplitude (MEP) and inspiratory mouth occlusion pressures (P 0.1 ) were evaluated in 17 healthy individuals (age=27±5 years) compared to Sham. Single nucleotide polymorphisms (SNPs) in genes linked with mechanisms of AIH induced phrenic motor plasticity ( BDNF, HTR 2A , TPH 2 , MAOA, NTRK 2 ) and neuronal plasticity (apolipoprotein E, APOE ) were tested. Variations in AIHH induced plasticity with age and sex were also analyzed. Additional experiments in humanized ( h ) ApoE knock-in rats were performed to test causality. Results: AIHH-induced changes in diaphragm MEP amplitudes were lower in individuals heterozygous for APOE 4 ( i.e., APOE 3/4 ) allele versus other APOE genotypes (p=0.048). No significant differences were observed between any other SNPs investigated, notably BDNFval/met ( all p>0.05 ). Males exhibited a greater diaphragm MEP enhancement versus females, regardless of age (p=0.004). Age was inversely related with change in P 0.1 within the limited age range studied (p=0.007). In hApoE 4 knock-in rats, AIHH-induced phrenic motor plasticity was significantly lower than hApoE 3 controls (p<0.05). Conclusions: APOE 4 genotype, sex and age are important biological determinants of AIHH-induced respiratory motor plasticity in healthy adults. ADDITION TO KNOWLEDGE BASE: Acute intermittent hypoxia (AIH) is a novel rehabilitation strategy to induce functional recovery of respiratory and non-respiratory motor systems in people with chronic spinal cord injury and/or neurodegenerative diseases. Since most AIH trials report considerable inter-individual variability in AIH outcomes, we investigated factors that potentially undermine the response to an optimized AIH protocol, acute intermittent hypercapnic-hypoxia (AIHH), in healthy humans. We demonstrate that genetics (particularly the lipid transporter, APOE ), age and sex are important biological determinants of AIHH-induced respiratory motor plasticity.

Spatiotemporal strategies adopted to walk at fast speed in high- and low-functioning individuals post-stroke: a cross-sectional study.

BACKGROUND: Walking at fast speed is a gait training strategy post-stroke. It is unknown how faster-than-preferred pace impacts spatiotemporal gait characteristics in survivors with different functional abilities. OBJECTIVE: To test the hypothesis that compared to high-functioning individuals, low-functioning individuals will be limited in modifying spatiotemporal gait parameters for walking at faster-than-preferred speed, and these limitations are associated with fear of falling. METHODS: Forty-two adults, 17.6 ± 14.6 months post-stroke, traversed an instrumented walkway at preferred and fast speeds. Participants were categorized to a low-functioning group (LFG) (n = 20; <0.45 m/s) and high-functioning group (HFG) (n = 22; ≥0.45 m/s). Cadence, step length, stance time and spatiotemporal asymmetry measures were calculated. The Modified Falls-efficacy Scale examined fear of falling. Multivariate and correlational analysis tested hypotheses. RESULTS: Increased speed from preferred to fast pace was significantly greater for HFG (0.27 ± 0.03 m/s) than LFG (0.10 ± 0.02 m/s) (p ≤ 0.001). Cadence gain from preferred to fast pace did not differ between groups. However, HFG exhibited greater change in paretic (∆6.1 ± 1.37 cm; p < .001) and non-paretic step lengths (∆4.5 ± 1.37 cm; p = .003) than LFG. Spatiotemporal asymmetry did not change for either group. Fear of falling had moderately positive correlation with ∆paretic step length (r = 0.43; p = .004) and ∆non-paretic step length (r = 0.32; p = .035). CONCLUSIONS: While both low- and high-functioning individuals used a step-lengthening strategy to walk at faster-than-preferred speeds, the gain in step lengths was limited in low-functioning individuals and was partially explained by falls-efficacy.

An evaluation of value-based outcomes for women admitted to a dialectical behaviour therapy integrated practice unit: a follow-up study.

BACKGROUND: An earlier evaluation (Fox et al., ) highlighted reductions in risk behaviours and restrictive practices for women admitted to low secure dialectical behaviour therapy (DBT) unit. Since then, a value-based healthcare model has been adopted. AIMS: To explore changes in health, social and psychological functioning, risk, quality of life, and in incidents of violence and restrictive practices, over the initial 12-month period of admission to a specialist DBT service. METHOD: Data were extracted from electronic clinical records for 41 women with emotionally unstable personality disorder admitted to a specialist integrated practice unit (IPU) providing a comprehensive DBT programme. Secondary analysis was conducted on an anonymous dataset of routinely collected outcome measures at baseline admission, and 6 and 12 months post-admission. ANOVAs and pairwise post hoc comparisons, and non-parametric equivalents, were conducted to examine changes in outcomes. RESULTS: Findings showed statistically significant improvements in mental health scores on the ReQOL (p<.01), global, wellbeing, problems, functioning and risk scores on the COREOM (all p<.01), and severe disturbance, emotional wellbeing, socioeconomic status, risk and need scores on the HoNOS-Secure (all p<.05). Significant reductions in risk behaviours (p<.01) and restrictive practices (p<.01) were also apparent. The most substantiative improvements were largely demonstrated over a 12-month admission period. CONCLUSIONS: Admission to the DBT IPU yielded significant improvements on outcomes pertaining to quality of life, psychological distress, and risk. Importantly, these are outcomes that aligned with patients' perceptions of recovery.

The 3-Meter Backward Walk Test (3MBWT): Reliability and validity in individuals with subacute and chronic stroke.

INTRODUCTION: Backward walking (BW) is an important gait adaptation and BW speed may be an important indicator of walking function and fall risk. However, the measurement characteristics of a standardized assessment of BW post-stroke have not been fully established. OBJECTIVES: To determine intra- and interrater reliability, concurrent validity and minimal detectable change (MDC) scores for the 3-Meter Backward Walk Test (3MBWT) post-stroke. METHODS: Thirty-four individuals with subacute and 29 individuals with chronic stroke participated. Two trials of comfortable BW was measured over a total distance of 5-meters, while speed was calculated during the middle 3-meters of the walking distance. Intra and interrater reliability were determined by comparing the two trials from one rater and simultaneous assessment of two raters, respectively. Two additional trials were performed and BW speed was calculated using 3MBWT and an instrumented walkway to determine concurrent validity. Intraclass correlation coefficients (ICC) estimated reliability and validity. The MDC was calculated from the standard error of measurement. RESULTS: Excellent ICC values were obtained for the 3MBWT in the subacute (interrater: ICC2,1 = 0.99; intrarater: ICC2,1 = 0.96; validity: ICC2,1 = 0.96) and chronic (interrater: ICC2,1 = 0.99; intrarater: ICC2,1 = 0.94; validity: ICC2,1 = 0.97) groups. The MDC was 0.07 m/s (subacute) and 0.11 m/s (chronic). CONCLUSIONS: Establishment of the 3MBWT as a reliable and valid measure in assessing BW speed is an important addition to the assessment toolbox for rehabilitation post-stroke.

Risk factors and outcomes associated with persistent vancomycin resistant Enterococcal Bacteremia.

BACKGROUND: Prior studies have identified that vancomycin resistant enterococcus (VRE) bacteremia that persists for four days or more is an independent predictor of mortality. Despite this, there is no published data to identify those patients at highest risk of developing persistent VRE bacteremia. METHODS: This was a single center, retrospective, case-control study of adult patients with a VRE bloodstream infection (BSI). Case patients were those with persistent bacteremia (≥ 4 days despite VRE-directed therapy) and control patients were those with non-persistent bacteremia. Logistic regression was used to assess risk factors associated with persistent VRE BSIs. Secondary outcomes included in-hospital mortality, recurrent bacteremia, and breakthrough bacteremia. RESULTS: During the study period, 24/108 (22%) patients had persistently positive blood cultures. Risk factors for persistent bacteremia included severe neutropenia (OR 2.13), 4 out of 4 positive index blood cultures (OR 11.29) and lack of source control (OR 11.88). In an unadjusted analysis, no statistically significant differences in in-hospital mortality (58% versus 40%; p = 0.121), recurrent bacteremia (17% versus 6%; p = 0.090), or breakthrough bacteremia (13% versus 7%; p = 0.402) were observed between groups. CONCLUSION: Patients with severe neutropenia, 4 out of 4 positive index blood culture bottles, and lack of source control were more likely to develop persistent VRE bacteremia despite directed antibiotic treatment.

Propagation of Pacemaker Activity and Peristaltic Contractions in the Mouse Renal Pelvis Rely on Ca2+-activated Cl- Channels and T-Type Ca2+ Channels.

The process of urine removal from the kidney occurs via the renal pelvis (RP). The RP demarcates the beginning of the upper urinary tract and is endowed with smooth muscle cells. Along the RP, organized contraction of smooth muscle cells generates the force required to move urine boluses toward the ureters and bladder. This process is mediated by specialized pacemaker cells that are highly expressed in the proximal RP that generate spontaneous rhythmic electrical activity to drive smooth muscle depolarization. The mechanisms by which peristaltic contractions propagate from the proximal to distal RP are not fully understood. In this study, we utilized a transgenic mouse that expresses the genetically encoded Ca2+ indicator, GCaMP3, under a myosin heavy chain promotor to visualize spreading peristaltic contractions in high spatial detail. Using this approach, we discovered variable effects of L-type Ca2+ channel antagonists on contraction parameters. Inhibition of T-type Ca2+ channels reduced the frequency and propagation distance of contractions. Similarly, antagonizing Ca2+-activated Cl- channels or altering the transmembrane Cl- gradient decreased contractile frequency and significantly inhibited peristaltic propagation. These data suggest that voltage-gated Ca2+ channels are important determinants of contraction initiation and maintain the fidelity of peristalsis as the spreading contraction moves further toward the ureter. Recruitment of Ca2+-activated Cl- channels, likely Anoctamin-1, and T-type Ca2+ channels are required for efficiently conducting the depolarizing current throughout the length of the RP. These mechanisms are necessary for the efficient removal of urine from the kidney.

Age-Based Tracks: A Method to Tailor Autism Diagnostic Evaluation in Large-Scale Autism Specialty Centers.

This paper describes a proposed model of diagnostic evaluation for autism spectrum disorder (ASD) at a large-scale ASD specialty center. Our center has implemented age-based diagnostic tracks within an interdisciplinary team evaluation approach to assessing ASD. Data were collected as part of a program evaluation and included responses from provider surveys as well as patient medical record reviews. The results from 803 patients were included. The diagnostic outcomes, time for evaluation, and appropriateness of referral were analyzed in patients referred to the Younger (n = 155) and Older (n = 648) diagnostic tracks. In 92.8% of cases referred to the clinic's standard team evaluation model, the provider teams were able to make a diagnostic decision within the allotted evaluation time. The results from an additional diagnostic pathway, termed the Autism Psych Team (APT), within the older track were also presented. The intake providers had the option to triage older patients to this pathway when they anticipated that the patient might be diagnostically complex. Most patients (45.1%) triaged to the APT were referred due to psychiatric complexity. In 96% of APT cases, the APT providers felt the patient was an appropriate referral. Overall, these results suggest a method to efficiently triage patients to diagnostic models equipped to serve them within a high-volume ASD center.