Spectral features of non-nutritive suck dynamics in extremely preterm infants.

Background: Non-nutritive suck (NNS) is used to promote ororhythmic patterning and assess oral feeding readiness in preterm infants in the neonatal intensive care unit (NICU). While time domain measures of NNS are available in real time at cribside, our understanding of suck pattern generation in the frequency domain is limited. The aim of this study is to model the development of NNS in the frequency domain using Fourier and machine learning (ML) techniques in extremely preterm infants (EPIs). Methods: A total of 117 EPIs were randomized to a pulsed or sham orocutaneous intervention during tube feedings 3 times/day for 4 weeks, beginning at 30 weeks post-menstrual age (PMA). Infants were assessed 3 times/week for NNS dynamics until they attained 100% oral feeding or NICU discharge. Digitized NNS signals were processed in the frequency domain using two transforms, including the Welch power spectral density (PSD) method, and the Yule-Walker PSD method. Data analysis proceeded in two stages. Stage 1: ML longitudinal cluster analysis was conducted to identify groups (classes) of infants, each showing a unique pattern of change in Welch and Yule-Walker calculations during the interventions. Stage 2: linear mixed modeling (LMM) was performed for the Welch and Yule-Walker dependent variables to examine the effects of gestationally-aged (GA), PMA, sex (male, female), patient type [respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD)], treatment (NTrainer, Sham), intervention phase [1, 2, 3], cluster class, and phase-by-class interaction. Results: ML of Welch PSD method and Yule-Walker PSD method measures revealed three membership classes of NNS growth patterns. The dependent measures peak_Hz, PSD amplitude, and area under the curve (AUC) are highly dependent on PMA, but show little relation to respiratory status (RDS, BPD) or somatosensory intervention. Thus, neural regulation of NNS in the frequency domain is significantly different for each identified cluster (classes A, B, C) during this developmental period. Conclusions: Efforts to increase our knowledge of the evolution of the suck central pattern generator (sCPG) in preterm infants, including NNS rhythmogenesis will help us better understand the observed phenotypes of NNS production in both the frequency and time domains. Knowledge of those features of the NNS which are relatively invariant vs. other features which are modifiable by experience will likewise inform more effective treatment strategies in this fragile population.

Somatosensory Modulation of Salivary Gene Expression and Oral Feeding in Preterm Infants: Randomized Controlled Trial.

BACKGROUND: Despite numerous medical advances in the care of at-risk preterm neonates, oral feeding still represents one of the first and most advanced neurological challenges facing this delicate population. Objective, quantitative, and noninvasive assessment tools, as well as neurotherapeutic strategies, are greatly needed in order to improve feeding and developmental outcomes. Pulsed pneumatic orocutaneous stimulation has been shown to improve nonnutritive sucking (NNS) skills in preterm infants who exhibit delayed or disordered nipple feeding behaviors. Separately, the study of the salivary transcriptome in neonates has helped identify biomarkers directly linked to successful neonatal oral feeding behavior. The combination of noninvasive treatment strategies and transcriptomic analysis represents an integrative approach to oral feeding in which rapid technological advances and personalized transcriptomics can safely and noninvasively be brought to the bedside to inform medical care decisions and improve care and outcomes. OBJECTIVE: The study aimed to conduct a multicenter randomized control trial (RCT) to combine molecular and behavioral methods in an experimental conceptualization approach to map the effects of PULSED somatosensory stimulation on salivary gene expression in the context of the acquisition of oral feeding habits in high-risk human neonates. The aims of this study represent the first attempt to combine noninvasive treatment strategies and transcriptomic assessments of high-risk extremely preterm infants (EPI) to (1) improve oral feeding behavior and skills, (2) further our understanding of the gene ontology of biologically diverse pathways related to oral feeding, (3) use gene expression data to personalize neonatal care and individualize treatment strategies and timing interventions, and (4) improve long-term developmental outcomes. METHODS: A total of 180 extremely preterm infants from three neonatal intensive care units (NICUs) will be randomized to receive either PULSED or SHAM (non-pulsing) orocutaneous intervention simultaneous with tube feedings 3 times per day for 4 weeks, beginning at 30 weeks postconceptional age. Infants will also be assessed 3 times per week for NNS performance, and multiple saliva samples will be obtained each week for transcriptomic analysis, until infants have achieved full oral feeding status. At 18 months corrected age (CA), infants will undergo neurodevelopmental follow-up testing, the results of which will be correlated with feeding outcomes in the neo-and post-natal period and with gene expression data and intervention status. RESULTS: The ongoing National Institutes of Health funded randomized controlled trial R01HD086088 is actively recruiting participants. The expected completion date of the study is 2021. CONCLUSIONS: Differential salivary gene expression profiles in response to orosensory entrainment intervention are expected to lead to the development of individualized interventions for the diagnosis and management of oral feeding in preterm infants. TRIAL REGISTRATION: ClinicalTrials.gov NCT02696343; https://clinicaltrials.gov/ct2/show/NCT02696343 (Archived by WebCite at http://www.webcitation.org/6r5NbJ9Ym).

Understanding the treatment of attention deficit hyperactivity disorder in newly diagnosed adult patients in general practice: a UK database study.

BACKGROUND: Adult attention deficit hyperactivity disorder (ADHD) has been largely ignored in psychiatric and general practice guidance until recently. Adult ADHD has a high social and medical burden, but health care is not well described in the UK. The main study objective was to evaluate a primary care adult ADHD population in terms of prescribing and health care contact rates. METHODS: This was a retrospective observational study using data from the Clinical Practice Research Database from January 1, 2002 to July 31, 2011. Adult patients with an incident ADHD diagnosis or ADHD medication were identified as having been free of ADHD medication or diagnoses in the previous 2 years. Patients were followed for 12-24 months after diagnosis. RESULTS: Of the 663 patients with ADHD in the cohort, 54.1% were prescribed ADHD medication during the observation period. During the first 6 months, 34.2% of patients initiated methylphenidates and 14.0% atomoxetine. In total, 36.3% patients were referred to secondary care psychiatry during observation, with the remaining population (63.7%) never having a referral. Most of the referrals were before diagnosis in primary care. At the end of the observation period, 16.2% of patients were on antipsychotics, 17.3% hypnotics, and 34.8% antidepressants or anxiolytics; however, some patients appeared to be prescribed antipsychotic or antidepressant medications even if they did not have an observable diagnosis in their records. Health care contact rates (general practitioner or hospital) increased by 39.2% post-diagnosis (incidence rate ratio: 1.39; 95% confidence interval: 1.32, 1.47), which may be related to the need for medication monitoring and titration. CONCLUSION: This study has shown in primary care that there is relatively low use of ADHD medication, low referrals into secondary care, high rates of usage of psychiatric non-ADHD medications for different indications, and an increasing burden in terms of health care contacts in adult ADHD patients post-diagnosis.

Cost-utility of exenatide once weekly compared with insulin glargine in patients with type 2 diabetes in the UK.

OBJECTIVE: To compare the cost-utility of exenatide once weekly (EQW) and insulin glargine in patients with type 2 diabetes in the United Kingdom (UK). RESEARCH DESIGN AND METHODS: The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with type 2 diabetes treated with EQW or insulin glargine. Treatment effects and patient baseline characteristics (mean age: 58 years, mean glycohaemoglobin: 8.3%) were taken from the DURATION-3 study. Unit costs and health state utility values were derived from published sources. As the price of EQW is not yet known, the prices of two currently available glucagon-like peptide-1 products were used as benchmarks. To reflect diabetes progression, patients started on EQW switched to insulin glargine after 5 years. The analysis was conducted from the perspective of the UK National Health Service over a time horizon of 50 years with costs and outcomes discounted at 3.5%. Sensitivity analyses explored the impact of changes in input data and assumptions and investigated the cost utility of EQW in specific body mass index (BMI) subgroups. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) for EQW compared with insulin glargine. RESULTS: At a price equivalent to liraglutide 1.2 mg, EQW was more effective and more costly than insulin glargine, with a base case ICER of £10,597 per quality-adjusted life-year (QALY) gained. EQW was associated with an increased time to development of any diabetes-related complication of 0.21 years, compared with insulin glargine. Three BMI subgroups investigated (<30, 30-35 and >35 kg/m(2)) reported ICERs for EQW compared with insulin glargine ranging from £9425 to £12,956 per QALY gained. CONCLUSIONS: At the prices investigated, the cost per QALY gained for EQW when compared with insulin glargine in type 2 diabetes in the UK setting, was within the range normally considered cost effective by NICE. Cost effectiveness in practice will depend on the final price of EQW and the extent to which benefits observed in short-term randomised trials are replicated in long-term use.

Analysis of costs by CD4 count category for the darunavir/r 600/100 mg bid and control protease inhibitor arms of the POWER 1 and 2 trials.

BACKGROUND: HIV-infected people with low CD4 counts are at higher risk of AIDS and incur increased health care costs from in-patient stays and medications. METHOD: In the POWER 1 and 2 trials, patients were treated with optimized nucleoside reverse transcriptase inhibitors and optional enfuvirtide (T-20), plus darunavir/ritonavir (DRV/r) or control protease inhibitor (PI). UK data on costs of care by CD4 count were combined with the data on antiretroviral treatment use and CD4 counts from the POWER trials to calculate expected health care costs. RESULTS: The mean annual UK cost of care (excluding antiretrovirals [ARVs]) was 23,780 pounds, 13,762 pounds, 7,032 pounds, and 7,032 pounds for patients with CD4 <50, 50-200, 200-350, and >350 cells/muL respectively. In the POWER trials, at week 48, the proportions of patients with CD4 counts in these categories were 7%, 36%, 29%, and 27% for the DRV/r arm versus 23%, 28%, 27%, and 22% for the control PI arm. The mean predicted annual per-patient cost of care was 11,170 pounds for DRV/r versus 12,873 pounds for control PI. CONCLUSION: By raising CD4 counts to levels where the risk of AIDS events is reduced, DRV/r treatment is predicted to lower patient care costs for ARV-experienced, HIV-infected individuals in the first year of treatment.

Extracorporeal membrane oxygenation in piglets using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201).

PURPOSE: The purpose of this study was to determine if the polymerized bovine hemoglobin-based oxygen-carrying solution HBOC-201 is an acceptable substitute for blood in a healthy porcine, extracorporeal membrane oxygenation (ECMO) model. METHODS: Ten piglets (15 to 25 kg) were placed on venoarterial ECMO. Four animals received blood-primed ECMO, and 6 animals received HBOC-201-primed ECMO. Hemodynamic variables, urine output, blood gas analyses, complete blood counts, and lactate levels were followed for 6 hours. Data were analyzed using a nonparametric sign test and repeated measures analysis of variance (ANOVA). RESULTS: All animals survived the 6-hour ECMO procedure. Heart rate, mean arterial pressure, urine output, and serum lactate levels were not significantly different between groups. Postpriming volume was 176 +/- 156 mL in the blood group. None of the animals in the HBOC-201 group required additional volume to maintain target flow during ECMO (P <.05). Arterial pH, pO2, and oxygen content between groups were not significantly different. Hematocrit for the HBOC-201 group was significantly (P <.05) lower than the blood group. CONCLUSIONS: HBOC-201-primed ECMO in a healthy porcine model showed similar hemodynamics and equivalent oxygen carrying capacity to blood-primed ECMO. Postpriming volume requirement was decreased significantly in the HBOC group. ECMO using HBOC-201 instead of blood appears promising and warrants further investigation.

A 16-year neonatal/pediatric extracorporeal membrane oxygenation transport experience.

OBJECTIVE: To characterize the population and survival of neonatal and pediatric patients transported by Wilford Hall Medical Center (WHMC) on extracorporeal membrane oxygenation (ECMO) since 1985. STUDY DESIGN: A retrospective chart, literature, and database review of pediatric and neonatal patients transported on ECMO by the WHMC ECMO transport team. In addition, a subpopulation analysis was performed comparing neonates with meconium aspiration syndrome (MAS) placed on ECMO at WHMC with those infants with MAS transported on ECMO. Characteristics of interest for this comparison included disease severity before ECMO, age at initiation of ECMO, survival, ECMO-related complications, and duration of ECMO support. RESULTS: Forty-two patients transported on ECMO were identified: 23 neonatal respiratory cases (survival 57%), 7 pediatric respiratory cases (survival 71%), 4 cardiac cases (survival 50%), and 8 extra-institutional ECMO transports (survival 63%). In the MAS subpopulation, there was significantly greater survival in the in-house group--97% (31/32)--than in the ECMO transport group--75% (9/12); there were no other significant differences between these groups. Overall, no ECMO-related complications leading to patient demise could be identified in the ECMO transport group. CONCLUSIONS: ECMO transport, although demonstrating acceptable survival, is a risk-laden modality that should not replace early referral to an ECMO center.