More beads, more peristaltic reserve, better outcomes: factors predicting postoperative dysphagia after magnetic sphincter augmentation.

INTRODUCTION: Magnetic sphincter augmentation (MSA) offers a minimally invasive anti-reflux alternative to fundoplication for gastroesophageal reflux disease. The most common side effect of MSA is dysphagia, which may require dilation or even device removal. The incidence of dysphagia may be reduced by MSA sizing and preoperative motility studies. Multiple rapid swallows (MRS) is a provocative maneuver during high-resolution esophageal manometry (HRM) that assesses peristaltic reserve. We evaluated factors predicting development of dysphagia following MSA. MATERIALS AND METHODS: A retrospective review of a prospectively maintained database identified patients undergoing MSA. Preoperative work-up included barium swallow, esophagogastroduodenoscopy, and esophageal manometry. Peristaltic augmentation was defined as a ratio > 1 of the distal contractile integral (DCI) following MRS and the mean DCI of the 10 baseline wet swallows during manometry. Demographics, MSA implant size, and postoperative symptom data were gathered on all patients. RESULTS: Sixty-eight patients underwent MSA. Mean age was 51.7 years, average BMI was 25.8 kg/m2. 15 (22.1%) of patients had severe dysphagia requiring endoscopic dilation. Peristaltic augmentation with MRS was significantly higher in patients without dysphagia (46.1% vs 6.3% p = 0.026). 33.3% of patients requiring dilatation exhibited complete absence of smooth muscle contraction following MRS (DCI = 0). The ratio of the DCI of MRS/wet swallows predicting dysphagia following MSA was 0.56. Patients with a small (12-14 beads) versus a larger MSA implant (15-17 beads) had a significantly higher rate of postoperative dysphagia (58.5% vs 30.0% p = 0.026). CONCLUSION: Adequate peristaltic reserve and larger device size correlate with decreased incidence of dysphagia following MSA implantation without compromising the anti-reflux barrier. Routine assessment of peristaltic reserve during preoperative HRM should be considered prior to MSA placement.

Pre-Existing Maternal Antibodies Cause Rapid Prenatal Rejection of Allotransplants in the Mouse Model of In Utero Hematopoietic Cell Transplantation.

In utero hematopoietic cell transplantation (IUHCT) is a nonmyeloablative nonimmunosuppressive alternative to postnatal hematopoietic stem cell transplantation for the treatment of congenital hemoglobinopathies. Anti-HLA donor-specific Abs (DSA) are associated with a high incidence of graft rejection following postnatal hematopoietic stem cell transplantation. We determine if DSA present in the mother can similarly cause graft rejection in the fetus following IUHCT. Ten million C57BL/6 (B6, H2kb) bone marrow cells were transplanted in utero into gestational day 14 BALB/c (H2kd) fetuses. The pregnant BALB/c dams carrying these fetuses either had been previously sensitized to B6 Ag or were injected on gestational days 13-15 with serum from B6-sensitized BALB/c females. Maternal-fetal Ab transmission, Ab opsonization of donor cells, chimerism, and frequency of macrochimeric engraftment (chimerism >1%) were assessed by flow cytometry. Maternal IgG was transmitted to the fetus and rapidly opsonized donor cells following IUHCT. Donor cell rejection was observed as early as 4 h after IUHCT in B6-sensitized dams and 24 h after IUHCT in dams injected with B6-sensitized serum. Efficient opsonization was strongly correlated with decreased chimerism. No IUHCT recipients born to B6-sensitized dams or dams injected with B6-sensitized serum demonstrated macrochimeric engraftment at birth compared with 100% of IUHCT recipients born to naive dams or dams injected with naive serum (p < 0.001). In summary, maternal donor-specific IgG causes rapid, complete graft rejection in the fetus following IUHCT. When a third-party donor must be used for clinical IUHCT, the maternal serum should be screened for DSA to optimize the chance for successful engraftment.

Amniotic Fluid Concentrations of Glial Fibrillary Acidic Protein Do Not Correlate with Prenatal Metrics in Fetuses with Myelomeningocele.

INTRODUCTION: We investigated the correlation of amniotic fluid (AF) concentrations of glial fibrillary acidic protein (GFAP) with prenatal features of myelomeningocele (MMC) and neurodevelopmental outcome after fetal MMC (fMMC) surgery. MATERIALS AND METHODS: AF was collected during fMMC surgery between December 2012 and November 2015. AF-GFAP concentration was determined by ELISA. Retrospective chart review identified the characteristics of the defect. Data regarding delivery and 1-year neurodevelopmental outcome was collected from The Children's Hospital of Philadelphia fMMC Registry. RESULTS: Eighty-two AF samples were collected from fMMC surgeries. Perinatal data were obtained from 77 subjects, and 1-year follow-up data from 65 subjects. GFAP concentrations were significantly elevated in MMC compared to myeloschisis (24.1 ± 2.9 and 10.3 ± 1.5 ng/mL; p < 0.0001). A larger percentage of subjects with myeloschisis defects delivered before their scheduled due date (myeloschisis 88.5%; MMC 55.0%; p = 0.003) and delivered at an earlier mean gestational age (34.6 ± 0.4 weeks, n = 26) compared to those with MMC defects (35.2 ± 0.4 weeks, n = 51) (p = 0.04). DISCUSSION: AF-GFAP levels differentiate between MMC and myeloschisis, and raise interesting questions regarding the clinical significance between the 2 types of defects.

Patient-Specific Classification of ICU Sedation Levels From Heart Rate Variability.

OBJECTIVE: To develop a personalizable algorithm to discriminate between sedation levels in ICU patients based on heart rate variability. DESIGN: Multicenter, pilot study. SETTING: Several ICUs at Massachusetts General Hospital, Boston, MA. PATIENTS: We gathered 21,912 hours of routine electrocardiogram recordings from a heterogenous group of 70 adult ICU patients. All patients included in the study were mechanically ventilated and were receiving sedatives. MEASUREMENTS AND MAIN RESULTS: As "ground truth" for developing our method, we used Richmond Agitation Sedation Scale scores grouped into four levels denoted "comatose" (-5), "deeply sedated" (-4 to -3), "lightly sedated" (-2 to 0), and "agitated" (+1 to +4). We trained a support vector machine learning algorithm to calculate the probability of each sedation level from heart rate variability measures derived from the electrocardiogram. To estimate algorithm performance, we calculated leave-one-subject out cross-validated accuracy. The patient-independent version of the proposed system discriminated between the four sedation levels with an overall accuracy of 59%. Upon personalizing the system supplementing the training data with patient-specific calibration data, consisting of an individual's labeled heart rate variability epochs from the preceding 24 hours, accuracy improved to 67%. The personalized system discriminated between light- and deep-sedation states with an average accuracy of 75%. CONCLUSIONS: With further refinement, the methodology reported herein could lead to a fully automated system for depth of sedation monitoring. By enabling monitoring to be continuous, such technology may help clinical staff to monitor sedation levels more effectively and to reduce complications related to over- and under sedation.

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele.

BACKGROUND: Cell-free RNA in amniotic fluid supernatant reflects developmental changes in gene expression in the living fetus, which includes genes that are specific to the central nervous system. Although it has been previously shown that central nervous system-specific transcripts are present in amniotic fluid supernatant, it is not known whether changes in the amniotic fluid supernatant transcriptome reflect the specific pathophysiologic condition of fetal central nervous system disorders. In myelomeningocele, there is open communication between the central nervous system and amniotic fluid. OBJECTIVES: The purpose of this study was to identify molecular pathophysiologic changes and novel disease mechanisms that are specific to myelomeningocele by the analysis of amniotic fluid supernatant cell-free RNA in fetuses with open myelomeningocele. STUDY DESIGN: Amniotic fluid supernatant was collected from 10 pregnant women at the time of the open myelomeningocele repair in the second trimester (24.5±1.0 weeks); 10 archived amniotic fluid supernatant from sex and gestational age-matched euploid fetuses without myelomeningocele were used as controls (20.9±0.9 weeks). Differentially regulated gene expression patterns were analyzed with the use of human genome expression arrays. RESULTS: Fetuses with myelomeningocele had 284 differentially regulated genes (176 up- and 108 down-regulated) in amniotic fluid supernatant. Known genes that were associated with myelomeningocele (PRICKLE2, GLI3, RAB23, HES1, FOLR1) and novel dysregulated genes were identified in association with neurodevelopment and neuronal regeneration (up-regulated, GAP43 and ZEB1) or axonal growth and guidance (down-regulated, ACAP1). Pathway analysis demonstrated a significant contribution of inflammation to disease and a broad influence of Wnt signaling pathways (Wnt1, Wnt5A, ITPR1). CONCLUSION: Transcriptomic analyses of living fetuses with myelomeningocele with the use of amniotic fluid supernatant cell-free RNA demonstrated differential regulation of specific genes and molecular pathways relevant to this central nervous system disorder, which resulted in a new understanding of pathophysiologic changes. The data also suggested the importance of pathways that involve secondary disease, such as inflammation, in myelomeningocele. These newly identified pathways may lead to hypotheses that can test novel therapeutic targets as adjuncts to fetal surgical repair.

The Intravenous Route of Injection Optimizes Engraftment and Survival in the Murine Model of In Utero Hematopoietic Cell Transplantation.

In utero hematopoietic cell transplantation (IUHCT) has the potential to treat a number of congenital hematologic disorders. Clinical application is limited by low levels of donor engraftment. Techniques that optimize donor cell delivery to the fetal liver (FL), the hematopoietic organ at the time of IUHCT, have the potential to enhance engraftment and the clinical success of IUHCT. We compared the 3 clinically applicable routes of injection (intravenous [i.v.], intraperitoneal [i.p.], and intrahepatic [i.h.]) and assessed short- and long-term donor cell engraftment and fetal survival in the murine model of IUHCT. We hypothesized that the i.v. route would promote direct donor cell homing to the FL, resulting in increased engraftment and allowing for larger injectate volumes without increased fetal mortality. We demonstrate that the i.v. route results in (1) rapid diffuse donor cell population of the FL compared with delayed diffuse engraftment after the i.p. and i.h. routes; (2) higher FL and spleen engraftment at early prenatal time points; (3) enhanced stable long-term peripheral blood donor cell engraftment; and (4) improved survival at higher injectate volumes, allowing for higher donor cell doses and increased long-term engraftment. These findings support the use of an i.v. route for clinical protocols of IUHCT.

Automatic Classification of Sedation Levels in ICU Patients Using Heart Rate Variability.

OBJECTIVE: To explore the potential value of heart rate variability features for automated monitoring of sedation levels in mechanically ventilated ICU patients. DESIGN: Multicenter, pilot study. SETTING: Several ICUs at Massachusetts General Hospital, Boston, MA. PATIENTS: Electrocardiogram recordings from 40 mechanically ventilated adult patients receiving sedatives in an ICU setting were used to develop and test the proposed automated system. MEASUREMENTS AND MAIN RESULTS: Richmond Agitation-Sedation Scale scores were acquired prospectively to assess patient sedation levels and were used as ground truth. Richmond Agitation-Sedation Scale scores were grouped into four levels, denoted "unarousable" (Richmond Agitation- Sedation Scale = -5, -4), "sedated" (-3, -2, -1), "awake" (0), "agitated" (+1, +2, +3, +4). A multiclass support vector machine algorithm was used for classification. Classifier training and performance evaluations were carried out using leave-oneout cross validation. An overall accuracy of 69% was achieved for discriminating between the four levels of sedation. The proposed system was able to reliably discriminate (accuracy = 79%) between sedated (Richmond Agitation-Sedation Scale < 0) and nonsedated states (Richmond Agitation-Sedation Scale > 0). CONCLUSIONS: With further refinement, the methodology reported herein could lead to a fully automated system for depth of sedation monitoring. By enabling monitoring to be continuous, such technology may help clinical staff to monitor sedation levels more effectively and to reduce complications related to over- and undersedation.

Response Rates to Anticonvulsant Trials in Patients with Triphasic-Wave EEG Patterns of Uncertain Significance.

BACKGROUND: Generalized triphasic waves (TPWs) occur in both metabolic encephalopathies and non-convulsive status epilepticus (NCSE). Empiric trials of benzodiazepines (BZDs) or non-sedating AED (NSAEDs) are commonly used to differentiate the two, but the utility of such trials is debated. The goal of this study was to assess response rates of such trials and investigate whether metabolic profile differences affect the likelihood of a response. METHODS: Three institutions within the Critical Care EEG Monitoring Research Consortium retrospectively identified patients with unexplained encephalopathy and TPWs who had undergone a trial of BZD and/or NSAEDs to differentiate between ictal and non-ictal patterns. We assessed responder rates and compared metabolic profiles of responders and non-responders. Response was defined as resolution of the EEG pattern and either unequivocal improvement in encephalopathy or appearance of previously absent normal EEG patterns, and further categorized as immediate (within <2 h of trial initiation) or delayed (>2 h from trial initiation). RESULTS: We identified 64 patients with TPWs who had an empiric trial of BZD and/or NSAED. Most patients (71.9%) were admitted with metabolic derangements and/or infection. Positive clinical responses occurred in 10/53 (18.9%) treated with BZDs. Responses to NSAEDs occurred in 19/45 (42.2%), being immediate in 6.7%, delayed but definite in 20.0%, and delayed but equivocal in 15.6%. Overall, 22/64 (34.4%) showed a definite response to either BZDs or NSAEDs, and 7/64 (10.9%) showed a possible response. Metabolic differences of responders versus non-responders were statistically insignificant, except that the 48-h low value of albumin in the BZD responder group was lower than in the non-responder group. CONCLUSIONS: Similar metabolic profiles in patients with encephalopathy and TPWs between responders and non-responders to anticonvulsants suggest that predicting responders a priori is difficult. The high responder rate suggests that empiric trials of anticonvulsants indeed provide useful clinical information. The more than twofold higher response rate to NSAEDs suggests that this strategy may be preferable to BZDs. Further prospective investigation is warranted.

Laparoscopic needle-assisted inguinal hernia repair in 495 children.

Minimally invasive surgery for inguinal hernia repair in children has been a controversial topic for pediatric surgeons. Our method for inguinal hernia repair using laparoscopic techniques has comparable outcomes to the standard open technique. We describe our technique and experience with the laparoscopic needle-assisted repair of inguinal hernia (LNAR). We report 502 cases (710 hernias) from 2009 to 2013 by 3 surgeons. We reviewed our prospectively collected outcomes database of all patients receiving LNAR from 1/2009 to 3/2013. 502 cases in 495 patients <13 years old with 710 inguinal hernias were identified for analysis and review. Hernia repair is accomplished with a single-port needle-assisted technique. After identification of a patent processus vaginalis, the internal ring is encircled in an extraperitoneal plane using a 22G-Touhy needle for placement of a purse-string suture, tied extracorporally, and buried beneath the skin. The technique was standardized for all cases. 710 inguinal hernias were laparoscopically repaired in 495 patients (408 boys and 87 girls) age range 11 days to 12.8 years (mean 29.2 months; median 15.5 months). 294 patients had unilateral repair (199R and 95L) and 208 had bilateral repair. Mean operating time for unilateral was 20.5 min, and bilateral was 26.4 min. 21 minor complications were identified (9 superficial wound infections, 8 suture granulomas, and 4 recurrent hydroceles) and 4 recurrences. Mean time since surgery is 30 months (3-54 months). Mean follow-up was 10.7 months (0.3-38.4 months). Post-operative data show our technique is safe with a 4 % rate of minor complication. Recurrence rate was 0.56 % for the total number of hernias (4/710). This recurrence rate is comparable and in many cases less than open technique. Furthermore, laparoscopy objectively identifies asymptomatic or occult contralateral defect, uses a smaller incision, and eliminates dissection of the cord structures potentially reducing the risk of cord injury.

Dental Care Among Adults Age 65 and Older: United States, 2022.

Oral health is associated with overall health, especially in older adults (age 65 and older). Chronic conditions in older adults may affect oral health, and poor oral health may increase the risk of certain chronic conditions (1-3). Poor oral health has also been associated with increased cardiovascular disease risk (4). Several factors, including chronic conditions, health status, race, and income have been associated with reduced dental care use among older adults (5-9). This report describes the percentage of older adults who had a dental visit in the past 12 months by selected sociodemographic characteristics and chronic conditions using the 2022 National Health Interview Survey (NHIS). .

Fetal allotransplant recipients are resistant to graft-versus-host disease.

In utero hematopoietic cell transplantation (IUHCT) is an experimental treatment for congenital hemoglobinopathies, including Sickle cell disease and thalassemias. One of the principal advantages of IUHCT is the predisposition of the developing fetus toward immunologic tolerance. This allows for engraftment across immune barriers without immunosuppression and, potentially, decreased susceptibility to graft-versus-host disease (GVHD). We demonstrate fetal resistance to GVHD following T cell-replete allogeneic hematopoietic cell transplantation compared with the neonate. We show that this resistance is associated with elevated fetal serum interleukin-10 conducive to the induction of regulatory T cells (Tregs). Finally, we demonstrate that the adoptive transfer of Tregs from IUHCT recipients to neonates uniformly prevents GVHD, recapitulating the predisposition to tolerance observed after fetal allotransplantation. These findings demonstrate fetal resistance to GVHD following hematopoietic cell transplantation and elucidate Tregs as important contributors.

Emotion-based decision-making as a predictor of alcohol-related consequences in college students.

Student drinking during the college years can result in many adverse outcomes. Emotion-based decision-making (EBDM), or the use of emotional information to influence future plans and behavior, may lead to increased harmful consequences of alcohol. The current study examined both the number of types and total frequency of alcohol consequences as a function of EBDM. Undergraduate students from three large universities (n = 814) were assessed on EBDM and typical weekly drinking during their 2nd year of college, and alcohol-related consequences during their 2nd, 3rd, and 4th years. Alcohol-related consequences were operationalized both as unique types of consequences and total consequences experienced in the previous year. Latent growth modeling used EBDM in year 2 to predict unique and total alcohol consequences in years 2, 3, and 4. Students who endorsed higher levels of EBDM experienced a significantly increased total frequency of consequences over the three years, without differences in trajectory between students high and low on this construct. Participants with higher levels of EBDM experienced a significantly greater number of unique consequences at all time points, but these consequences increased at a significantly lower rate than individuals lower on this construct. Findings of this study indicate Emotion-Based Decision-Making may be a useful predictor of harmful consequences of student drinking over time.

A pilot randomized controlled trial of smartphone-assisted mindfulness-based intervention with contingency management for smokers with mood disorders.

Cigarette smoking disproportionately affects individuals with mood disorders, but smoking cessation interventions have modest effects in this population. Home mindfulness practice during abstinence incentivized via contingency management (CM) may help those in affective distress quit smoking. METHOD: Adult smokers receiving outpatient psychiatric treatment for mood disorders were randomized to receive a smartphone-assisted mindfulness-based smoking cessation intervention with contingency management (SMI-CM, n = 25) or enhanced standard treatment (EST, n = 24) with noncontingent rewards. Participants in SMI-CM were prompted to practice audio-guided mindfulness five times per day for 38 days (vs. no comparison intervention in EST), and received monetary incentives for carbon monoxide (CO) ≤ 6 ppm. The primary outcome was biochemically verified 7-day point prevalence abstinence rates 2, 4, and 13 weeks after a target quit day. RESULTS: Of the 49 participants, 63.3% were Latinx and 30.6% Black; 75.5% reported household incomes < $25,000. Abstinence rates for SMI-CM were 40.0%, 36.0%, and 16.0% versus 4.2%, 8.3%, and 4.2% in EST at weeks 2, 4, and 13. A generalized estimating equations (GEE) model showed significant overall differences in abstinence rates in SMI-CM versus EST (adjusted odds ratio [AOR] = 8.12, 95% CI = 1.42-46.6, p = .019). Those who received SMI-CM reported significantly greater reduction in smoking-specific experiential avoidance from baseline to 3 days prior to quit date (ß = -7.21, 95% CI = -12.1-2.33, p = .006). CONCLUSIONS: SMI-CM may increase cessation rates among smokers with mood disorders, potentially through reduced smoking-specific experiential avoidance. SMI-CM is a promising intervention, and warrants investigation in a fully powered randomized controlled trial (RCT). (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ICU delirium burden predicts functional neurologic outcomes.

BACKGROUND: We investigated the effect of delirium burden in mechanically ventilated patients, beginning in the ICU and continuing throughout hospitalization, on functional neurologic outcomes up to 2.5 years following critical illness. METHODS: Prospective cohort study of enrolling 178 consecutive mechanically ventilated adult medical and surgical ICU patients between October 2013 and May 2016. Altogether, patients were assessed daily for delirium 2941days using the Confusion Assessment Method for the ICU (CAM-ICU). Hospitalization delirium burden (DB) was quantified as number of hospital days with delirium divided by total days at risk. Survival status up to 2.5 years and neurologic outcomes using the Glasgow Outcome Scale were recorded at discharge 3, 6, and 12 months post-discharge. RESULTS: Of 178 patients, 19 (10.7%) were excluded from outcome analyses due to persistent coma. Among the remaining 159, 123 (77.4%) experienced delirium. DB was independently associated with >4-fold increased mortality at 2.5 years following ICU admission (adjusted hazard ratio [aHR], 4.77; 95% CI, 2.10-10.83; P < .001), and worse neurologic outcome at discharge (adjusted odds ratio [aOR], 0.02; 0.01-0.09; P < .001), 3 (aOR, 0.11; 0.04-0.31; P < .001), 6 (aOR, 0.10; 0.04-0.29; P < .001), and 12 months (aOR, 0.19; 0.07-0.52; P = .001). DB in the ICU alone was not associated with mortality (HR, 1.79; 0.93-3.44; P = .082) and predicted neurologic outcome less strongly than entire hospital stay DB. Similarly, the number of delirium days in the ICU and for whole hospitalization were not associated with mortality (HR, 1.00; 0.93-1.08; P = .917 and HR, 0.98; 0.94-1.03, P = .535) nor with neurological outcomes, except for the association between ICU delirium days and neurological outcome at discharge (OR, 0.90; 0.81-0.99, P = .038). CONCLUSIONS: Delirium burden throughout hospitalization independently predicts long term neurologic outcomes and death up to 2.5 years after critical illness, and is more predictive than delirium burden in the ICU alone and number of delirium days.

Associations between mindfulness and mental health outcomes: A systematic review of ecological momentary assessment research.

Objectives: Psychological science has taken up investigations of the effectiveness of mindfulness-based programs (MBPs) and mechanisms through which people benefit from mindfulness. Reliable and valid psychometric tools are essential components of psychological science, and efforts have been made to produce tools for the accurate measurement of mindfulness as a construct. However, trait measurement methods, which are commonly used, may not adequately assess mindfulness and mental health outcomes in a way that allows for mechanisms to be adequately tested. Intensive longitudinal assessment methods sample behavior and experience multiple times over a brief period of several days or weeks, and may be more appropriate methods for testing mechanisms of action. We provide a systematic review of published, peer-reviewed studies that used intensive longitudinal methods to investigate the effects of mindfulness on mental health outcomes. Methods: Articles were included in the systematic review if mindfulness measures and/or mindfulness interventions were a part of the study design and if intensive longitudinal methods were used to assess mindfulness or mental health outcomes. Results: Findings consistently demonstrated a positive association between mindfulness and mental health. Only two studies collected both trait and state measurements of either mindfulness or mental health outcomes, and results indicated that EMA produced larger effect sizes between mindfulness and mental health outcomes. Conclusions: Theorized associations between mindfulness and mental health are supported by the current EMA literature. Intensive longitudinal methods may produce more consistent and reliable results through increased sensitivity and ecological validity in that they examine the momentary relationships between mindfulness and mental health outcomes. Thus, intensive longitudinal assessment may be a more appropriate method for investigating hypothesized mechanisms of action in MBPs.

No pain is gain: A prospective evaluation of strict non-opioid pain control after pediatric appendectomy.

INTRODUCTION: Opiates are often prescribed after pediatric operations despite safety concerns and lack of evidence confirming superiority compared to other pain control modalities. In this study, we use daily parental surveys to prospectively evaluate a strict non-opioid pain control strategy after laparoscopic appendectomy. METHODS: After IRB approval, children who underwent laparoscopic appendectomy for nonperforated acute appendicitis were recruited to the study. For these patients, our standard practice is to provide instructions to administer alternating acetaminophen and ibuprofen over-the-counter (OTC) postoperatively, and no opiate prescriptions are written. Parents of enrolled children received a daily RedCap survey via text message or e-mail on postoperative days (POD) 1 through 5 to prospectively assess pain control and medication usage. Trends were compared across postoperative days. RESULTS: One hundred twenty patients were enrolled in the study, and none received opiate prescriptions. Postoperative pain survey response rates were 54% on POD1, 47% on POD2, 35% on POD3, 34% on POD4, and 29% on POD5. Pain level was 4.7 ±â€¯2.3 (out of 10) on POD1, and down-trended significantly each postoperative day to reach 0.7 ±â€¯1.2 by POD5. On POD1, 85% of parents administered OTC medications, which reduced significantly to 14% by POD5. Parent-reported success rates to manage pain by OTC regimen were 85% on POD1, 94% on POD2, 91% on POD3, and 100% on POD4 and POD5. CONCLUSION: Strict non-opioid pain control after appendectomy exhibits high performance based upon prospective parental surveys. This strategy should be implemented as standard of care and tested for application to other surgical conditions. LEVEL OF EVIDENCE: Level II.

Regulatory T cells promote alloengraftment in a model of late-gestation in utero hematopoietic cell transplantation.

In utero hematopoietic cell transplantation (IUHCT) has the potential to cure congenital hematologic disorders including sickle cell disease. However, the window of opportunity for IUHCT closes with the acquisition of T-cell immunity, beginning at approximately 14 weeks gestation, posing significant technical challenges and excluding from treatment fetuses evaluated after the first trimester. Here we report that regulatory T cells can promote alloengraftment and preserve allograft tolerance after the acquisition of T-cell immunity in a mouse model of late-gestation IUHCT. We show that allografts enriched with regulatory T cells harvested from either IUHCT-tolerant or naive mice engraft at 20 days post coitum (DPC) with equal frequency to unenriched allografts transplanted at 14 DPC. Long-term, multilineage donor cell chimerism was achieved in the absence of graft-versus-host disease or mortality. Decreased alloreactivity among recipient T cells was observed consistent with donor-specific tolerance. These findings suggest that donor graft enrichment with regulatory T cells could be used to successfully perform IUHCT later in gestation.

Automated tracking of level of consciousness and delirium in critical illness using deep learning.

Over- and under-sedation are common in the ICU, and contribute to poor ICU outcomes including delirium. Behavioral assessments, such as Richmond Agitation-Sedation Scale (RASS) for monitoring levels of sedation and Confusion Assessment Method for the ICU (CAM-ICU) for detecting signs of delirium, are often used. As an alternative, brain monitoring with electroencephalography (EEG) has been proposed in the operating room, but is challenging to implement in ICU due to the differences between critical illness and elective surgery, as well as the duration of sedation. Here we present a deep learning model based on a combination of convolutional and recurrent neural networks that automatically tracks both the level of consciousness and delirium using frontal EEG signals in the ICU. For level of consciousness, the system achieves a median accuracy of 70% when allowing prediction to be within one RASS level difference across all patients, which is comparable or higher than the median technician-nurse agreement at 59%. For delirium, the system achieves an AUC of 0.80 with 69% sensitivity and 83% specificity at the optimal operating point. The results show it is feasible to continuously track level of consciousness and delirium in the ICU.

Electroencephalogram Based Detection of Deep Sedation in ICU Patients Using Atomic Decomposition.

OBJECTIVE: This study was performed to evaluate how well states of deep sedation in ICU patients can be detected from the frontal electroencephalogram (EEG) using features based on the method of atomic decomposition (AD). METHODS: We analyzed a clinical dataset of 20 min of EEG recordings per patient from 44 mechanically ventilated adult patients receiving sedatives in an intensive care unit (ICU) setting. Several features derived from AD of the EEG signal were used to discriminate between awake and sedated states. We trained support vector machine (SVM) classifiers using AD features and compared the classification performance with SVM classifiers trained using standard spectral and entropy features using leave-one-subject-out validation. The potential of each feature to discriminate between awake and sedated states was quantified using area under the receiver operating characteristic curve (AUC). RESULTS: The sedation level classification system using AD was able to reliably discriminate between sedated and awake states achieving an average AUC of 0.90, which was significantly better () than performance achieved using spectral (AUC = 0.86) and entropy (AUC = 0.81) domain features. A combined feature set consisting of AD, entropy, and spectral features provided better discrimination (AUC = 0.91, ) than any individual feature set. CONCLUSIONS: Features derived from the atomic decomposition of EEG signals provide useful discriminative information about the depth of sedation in ICU patients. SIGNIFICANCE: With further refinement and external validation, the proposed system may be able to assist clinical staff with continuous surveillance of sedation levels in mechanically ventilated critically ill ICU patients.

Rationale, design and pilot feasibility results of a smartphone-assisted, mindfulness-based intervention for smokers with mood disorders: Project mSMART MIND.

BACKGROUND: Although individuals with psychiatric disorders are disproportionately affected by cigarette smoking, few outpatient mental health treatment facilities offer smoking cessation services. In this paper, we describe the development of a smartphone-assisted mindfulness smoking cessation intervention with contingency management (SMI-CM), as well as the design and methods of an ongoing pilot randomized controlled trial (RCT) targeting smokers receiving outpatient psychiatric treatment. We also report the results of an open-label pilot feasibility study. METHODS: In phase 1, we developed and pilot-tested SMI-CM, which includes a smartphone intervention app that prompts participants to practice mindfulness, complete ecological momentary assessment (EMA) reports 5 times per day, and submit carbon monoxide (CO) videos twice per day. Participants earned incentives if submitted videos showed CO≤6ppm. In phase 2, smokers receiving outpatient treatment for mood disorders are randomized to receive SMI-CM or enhanced standard treatment plus non-contingent CM (EST). RESULTS: The results from the pilot feasibility study (N=8) showed that participants practiced mindfulness an average of 3.4times/day (≥3min), completed 72.3% of prompted EMA reports, and submitted 68.0% of requested CO videos. Participants reported that the program was helpful overall (M=4.85/5) and that daily mindfulness practice was helpful for both managing mood and quitting smoking (Ms=4.50/5). CONCLUSIONS: The results from the feasibility study indicated high levels of acceptability and satisfaction with SMI-CM. The ongoing RCT will allow evaluation of the efficacy and mechanisms of action underlying SMI-CM for improving cessation rates among smokers with mood disorders.