Pharyngeal biorhythms during oral milk challenge in high-risk infants: Do they predict chronic tube feeding?

BACKGROUND: Eating difficulties are common in high-risk neonatal intensive care unit (NICU) infants; mechanisms remain unclear. Crib-side pharyngo-esophageal motility testing is utilized to assess contiguous swallowing physiology, and cross-system interplay with cardio-respiratory rhythms. Aims were to: (1) identify whether distinct pharyngeal rhythms exist during oral milk challenge (OMC), and (2) develop a chronic tube feeding risk prediction model in high-risk infants. METHODS: Symptomatic NICU infants (N = 56, 29.7 ± 3.7 weeks birth gestation) underwent pharyngo-esophageal manometry with OMC at 40.9 ± 2.5 weeks postmenstrual age (PMA). Exploratory cluster data analysis (partitioning around k-medoids) was performed to identify patient groups using pharyngeal contractile rhythm data (solitary swallows and swallows within bursts). Subsequently, (a) pharyngeal-esophageal, cardio-respiratory, and eating method characteristics were compared among patient groups using linear mixed models, and (b) chronic tube feeding prediction model was created using linear regression. RESULTS: Three distinct patient groups were identified with validity score of 0.6, and termed sparse (high frequency of solitary swallows), intermediate, or robust (high swallow rate within bursts). Robust group infants had: lesser pharyngeal and esophageal variability, greater deglutition apnea, pharyngeal activity, and esophageal activity (all p < 0.05), but less frequent heart rate decreases (p < 0.05) with improved clinical outcomes (milk transfer rate, p < 0.001, and independent oral feeding at discharge, p < 0.03). Chronic tube feeding risk = -11.37 + (0.22 × PMA) + (-0.73 × bronchopulmonary dysplasia) + (1.46 × intermediate group) + (2.57 × sparse group). CONCLUSIONS: Robust pharyngeal rhythm may be an ideal neurosensorimotor biomarker of independent oral feeding. Differential maturation of cranial nerve-mediated excitatory and inhibitory components involving foregut, airway, and cardiac rhythms distinguishes the physiologic and pathophysiologic basis of swallowing and cardio-respiratory adaptation.

Medical Mistrust and Adherence to Care Among a Heterogeneous Cohort of Women Living with HIV, Followed in a Large, U.S. Safety Net Clinic.

Purpose: To explore the relationship between medical mistrust, as measured by the Group-Based Medical Mistrust (GBMM) scale, and HIV care adherence among a cohort of minority women receiving care in a U.S. safety net clinic. Methods: English-, Spanish-, and Haitian Creole (Creole)-speaking patients with a recent history of nonadherence to care were surveyed. Results: English speakers endorsed the highest level of mistrust, followed by Spanish speakers and Creole speakers. Creole speakers endorsed lower mistrust, lower suspicion of providers, and lower levels of "perceived health care disparities." Higher mistrust was associated significantly with lower medication adherence, and lower rates of viral suppression (nonsignificant). Conclusion: Understanding perceptions of medical care and the relationship to HIV care adherence is an important step to addressing negative health outcomes for ethnic minority women with HIV. Clinical Trial Registration Number: NCT03738410.

Cognitive and motor deficits in older adults with HIV infection: Comparison with normal ageing and Parkinson's disease.

Despite the life-extending success of antiretroviral pharmacotherapy in HIV infection (HIV), the prevalence of mild cognitive impairment in HIV remains high. Near-normal life expectancy invokes an emerging role for age-infection interaction and a potential synergy between immunosenescence and HIV-related health factors, increasing risk of cognitive and motor impairment associated with degradation in corticostriatal circuits. These neural systems are also compromised in Parkinson's disease (PD), which could help model the cognitive deficit pattern in HIV. This cross-sectional study examined three groups, age 45-79 years: 42 HIV, 41 PD, and 37 control (CTRL) participants, tested at Stanford University Medical School and SRI International. Neuropsychological tests assessed executive function (EF), information processing speed (IPS), episodic memory (MEM), visuospatial processing (VSP), and upper motor (MOT) speed and dexterity. The HIV and PD deficit profiles were similar for EF, MEM, and VSP. Although only the PD group was impaired on MOT compared with CTRL, MOT scores were related to cognitive scores in HIV but not PD. Performance was not related to depressive symptoms, socioeconomic status, or CD4+ T-cell counts. The overlap of HIV-PD cognitive deficits implicates frontostriatal disruption in both conditions. The motor-cognitive score relation in HIV provides further support for the hypothesis that these processes share similar underlying mechanisms in HIV infection possibly expressed with or exacerbated by ageing.

Differentiating esophageal sensitivity phenotypes using pH-impedance in intensive care unit infants referred for gastroesophageal reflux symptoms.

BACKGROUND: To identify esophageal sensitivity phenotypes relative to acid (SAcid), bolus (SBolus), acid and bolus (SAcid+Bolus), and none (SNone) exposures in infants suspected with gastroesophageal reflux disease (GERD). METHODS: Symptomatic infants (N = 279) were evaluated for GERD at 42 (40-45) weeks postmenstrual age using 24-h pH-impedance. Symptom-associated probability (SAP) for acid and bolus components defined esophageal sensitivity: (1) SAcid as SAP ≥ 95% for acid (pH < 4), (2) SBolus as SAP ≥ 95% for bolus, (3) SAcid+Bolus as SAP ≥ 95% for acid and bolus, or (4) SNone as SAP < 95% for acid and bolus. RESULTS: Esophageal sensitivity prevalence (SAcid, SBolus, SAcid+Bolus, SNone) was 28 (10%), 94 (34%), 65 (23%), and 92 (33%), respectively. Emesis occurred more in SBolus and SAcid+Bolus vs SNone (p < 0.05). Magnitude (#/day) of cough and emesis events increased with SBolus and SAcid+Bolus vs SNone (p < 0.05). SAcid+Bolus had increased acid exposure vs SNone (p < 0.05). Distributions of feeding and breathing methods were distinct in infants with SBolus vs SNone (both, p < 0.05). Multivariate analysis revealed that arching and irritability events/day were lesser at higher PMAs (p < 0.001) and greater for infants on NCPAP (p < 0.01) with SBolus and SAcid+Bolus (p < 0.05). Coughs/day was greater at higher PMAs (p < 0.001) for infants with gavage and transitional feeding methods (p < 0.02) with SBolus and SAcid+Bolus (p < 0.05) but lesser with Trach (p < 0.001). Number of emesis events/day were greater with SBolus and SAcid+Bolus (p < 0.001). Sneezes/day decreased for infants on Trach (p = 0.02). CONCLUSIONS: Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. We differentiated esophageal sensitivity phenotypes in NICU infants referred for GERD symptoms using pH-impedance. Acid sensitivity alone was rare, which may explain poor response to acid suppressives; aerodigestive symptoms were predominantly linked with bolus spread. Magnitude of esophageal acid exposure and esophageal sensitivity to bolus spread may explain the pathophysiological basis for symptoms. IMPACT: Objective GERD diagnosis and reasons for symptoms in NICU infants remains unclear. Differentiation of esophageal sensitivities by acid and bolus components of GER reveal distinct symptom profiles, specifically the bolus component of GER significantly contributes to symptom occurrence. Acid only sensitivity to GER is rare, and acid-suppressive therapy alone may not improve symptoms in a majority of NICU infants. Magnitude of esophageal acid exposure and esophageal sensitivity to any bolus spread may explain the pathophysiological basis for symptoms. Feeding and breathing methods can influence the frequency and type of aerodigestive symptoms. GERD treatments should be individualized to the patient's GERD phenotype and likely also target the bolus component of GER.

Quantitative Digitography Measures Fine Motor Disturbances in Chronically Treated HIV Similar to Parkinson's Disease.

Introduction: Motor and cognitive deficits were compared in aging, chronically treated human immunodeficiency virus (HIV) people, people with mild-to-moderate stage Parkinson's disease (PD), and healthy controls. Methods: Groups consisted of 36 people with PD, 28 with HIV infection, and 28 healthy controls. Motor function was assessed with the Unified Parkinson's Disease Rating Scale (MDS-UPDRS-III) and a rapid alternating finger tapping (RAFT) task on an engineered keyboard known as Quantitative Digitography (QDG). Executive function, verbal memory, and visuospatial processing were assessed using standard neuropsychological tests. Results: HIV demonstrated RAFT deficits similar to PD such as reduced amplitude (P = 0.023) and greater amplitude variability (P = 0.019) in the index finger when compared to controls. This fine motor disturbance correlated with HIV's immune health, measured by their CD4+ T cell count (P < 0.01). The UPDRS did not yield motor differences between HIV and controls. Executive function and verbal memory were impaired in HIV (P = 0.006, P = 0.016, respectively), but not in PD; visuospatial processing was similarly impaired in HIV and PD (P < 0.05) although motor deficits predominated in PD. Conclusions: Fine motor bradykinesia measured quantitatively by QDG RAFT holds promise as a marker of motor decline related to current immune health in aging HIV patients and may be useful in longitudinal studies regarding mechanisms of immunosenescence vs. potential toxicity of combination antiretroviral therapy (cART) in this population. Additionally, motor and cognitive networks in HIV may be affected differently as the disease progresses as observed in the differential patterns of impairment between HIV and PD, providing insight into the mechanisms of brain deterioration in HIV.

Mechanisms of bradycardia in premature infants: Aerodigestive-cardiac regulatory-rhythm interactions.

OBJECTIVE: Eating difficulties coupled with cardiorespiratory spells delay acquisition of feeding milestones in convalescing neonates, and the mechanisms are unclear. Aims were to examine and compare the pharyngoesophageal-cardiorespiratory (PECR) response characteristics: (a) in control neonates and those with recurrent bradycardia spells; and (b) during pharyngeal stimulation when bradycardia occurs versus when no bradycardia occurs. METHODS: Preterm infants (N = 40, 27 ± 3 weeks gestation), underwent concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor to evaluate pharyngoesophageal motility, heart rate (HR), and respiration during graded abrupt pharyngeal sterile water stimuli. Infants with recurrent bradycardia (N = 28) and controls (N = 12) were evaluated at 38 (38-40) and 39 (38-40) weeks postmenstrual age, respectively. Comparisons were performed (a) between study and control groups; and (b) among HR responses of <80 BPM, 80-100 BPM, and >100 BPM. RESULTS: Overall, characteristics of PECR responses in infants with a history of recurrent bradycardia (vs. controls) did not differ (p > .05). However, when pharyngeal stimulus induced severe bradycardia (<80 BPM): prolonged respiratory rhythm change, increased pharyngeal activity, increased esophageal dysmotility (as evidenced by prolonged esophageal inhibition and motor activity), and prolonged lower esophageal sphincter relaxation were noted (all p < .05). CONCLUSIONS: In control infants and those with recurrent bradycardia, pharyngeal stimulation results in similar PECR response characteristics. However, when severe bradycardia occurs, PECR response characteristics are distinct. The mechanisms of severe bradycardia spells are related to abnormal prolongation of vagal inhibitory effects on cardiorespiratory rhythms in conjunction with prolonged esophageal inhibition and delays with terminal swallow.

Safety of Plasma Infusions in Parkinson's Disease.

BACKGROUND: Young plasma infusions have emerged as a potential treatment for neurodegenerative disease, and convalescent plasma therapy has been used safely in the management of viral pandemics. However, the effect of plasma therapy in Parkinson's disease (PD) is unknown. OBJECTIVES: The objective of this study was to determine the safety, tolerability, and feasibility of plasma infusions in people with PD. METHODS: A total of 15 people with clinically established PD, at least 1 cognitive complaint, and on stable therapy received 1 unit of young fresh frozen plasma twice a week for 4 weeks. Assessments and adverse effects were performed/reported on and off therapy at baseline, immediately after, and 4 weeks after the infusions ended. Adverse effects were also assessed during infusions. The primary outcomes were safety, tolerability, and feasibility. Exploratory outcomes included Unified Parkinson's Disease Rating Scale Part III off medication, neuropsychological battery, Parkinson's Disease Questionnaire-39, inflammatory markers (tumor necrosis factor-α, interleukin-6), uric acid, and quantitative kinematics. RESULTS: Adherence rate was 100% with no serious adverse effects. There was evidence of improvement in phonemic fluency (P = 0.002) and in the Parkinson's Disease Questionnaire-39 stigma subscore (P = 0.013) that were maintained at the delayed evaluation. Elevated baseline tumor necrosis factor-α levels decreased 4 weeks after the infusions ended. CONCLUSIONS: Young fresh frozen plasma was safe, feasible, and well tolerated in people with PD, without serious adverse effects and with preliminary evidence for improvements in phonemic fluency and stigma. The results of this study warrant further therapeutic investigations in PD and provide safety and feasibility data for plasma therapy in people with PD who may be at higher risk for severe complications of COVID-19. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Pharyngeal contractile and regulatory characteristics are distinct during nutritive oral stimulus in preterm-born infants: Implications for clinical and research applications.

BACKGROUND: Maturation of pharyngeal swallowing during neonatal oral feeding is unknown. Our objective was to evaluate pharyngeal functioning using high-resolution manometry (HRM) during nutritive oral stimulus and test the hypothesis that pharyngeal contractility and regulation are distinct in preterm-born infants. METHODS: High-resolution manometry data during oral milk feeding were analyzed for pharyngeal contractile (PhCI, mm Hg cm s) and regulatory (number and frequency of pharyngeal contractions and bursts, pharyngeal activity-to-quiescence ratio, upper esophageal sphincter nadir pressure) characteristics in 23 preterm (<38 weeks' gestation) and 18 full-term-born infants at term maturation. Mixed linear models and stepwise regression methods were used. RESULTS: Despite more oral feeding experiences (P < 0.05), preterm infants (vs full-term), consumed less milk volume (P < 0.001), had lesser pharyngeal contractions within bursts (P = 0.04), lower pharyngeal contraction frequency (P < 0.01), and lower pharyngeal activity (P = 0.03), but higher PhCI per individual contraction (P = 0.01). PhCI is higher for longer PMA (P < 0.05), higher UES nadir pressures (P < 0.05), and lower pharyngeal contraction frequency (P < 0.05). CONCLUSIONS: Nutritive oral milk stimulus provoked pharyngeal contractility characteristics is distinct in preterm-born. Despite more oral nutritive experiences, preterm infants had underdeveloped excitatory and inhibitory rhythmic activity. Cranial nerve IX and X effects on sensory-motor responses and feedback (excitation-inhibitory rhythm regulation) remain immature among preterm-born even at full-term maturational status. We speculate the relationship between PhCI and UES regulatory activity contributes to the observed differences in preterm and full-term infants.

Information processing deficit in older adults with HIV infection: A comparison with Parkinson's disease.

OBJECTIVE: Individuals with HIV treated with antiretroviral therapy can expect to reach average life span, making them susceptible to combined disease and aging effects on cognitive and motor functions. Slowed processing speed in HIV is a concern for cognitive and everyday functioning and is sensitive to declines in aging. We hypothesized that information processing (IP) deficits, over and above that expected with normal aging, would occur in older HIV patients similar to those observed in Parkinson's disease (PD) patients, with both conditions affecting frontostriatal pathways. METHOD: Groups comprised 26 individuals with HIV infection, 29 with mild-to-moderate PD, and 21 healthy controls (C). Speed of IP was assessed with the oral version of the Symbol Digit Modalities Test and the color naming condition of the Golden Stroop Task. RESULTS: The HIV group was impaired on speed of IP tasks compared with both the C and PD groups. Even after controlling for normal aging effects, older age in the HIV group correlated with IP slowing. Slower IP speed was associated with poorer general cognitive ability and more extrapyramidal motor signs in older HIV-infected individuals. CONCLUSIONS: The notable effects of impaired IP speed, over and above neurotypical age-related declines, indicate that older HIV-infected individuals may have an enhanced vulnerability for developing nonmotor and motor symptoms despite antiretroviral therapy. Assessing for oral IP speed may provide the unique opportunity to identify early signs of progressive clinical declines in HIV. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Defining pharyngeal contractile integral during high-resolution manometry in neonates: a neuromotor marker of pharyngeal vigor.

BACKGROUND: Pharyngeal contractility is critical for safe bolus propulsion. Pharyngeal contractile vigor can be measured by Pharyngeal Contractile Integral (PhCI): product of mean pharyngeal contractile amplitude, length, and duration. We characterized PhCI in neonates and examined the hypothesis that PhCI differs with mode of stimulation. METHODS: Nineteen neonates born at 38.6 (34-41) weeks gestation were evaluated at 42.9 (40.4-44.0) weeks postmenstrual age using high-resolution manometry (HRM). PhCI was calculated using: (a) Conventional and (b) Automated Swallow Detection algorithm (ASDA) methods. Contractility metrics of all pharyngeal regions were examined using mixed statistical models during spontaneous and adaptive state (pharyngeal and oral stimulus) swallowing. RESULTS: PhCI of oral stimuli swallows were distinct from pharyngeal stimuli and spontaneous swallows (P < 0.05). Correlation between conventional and ASDA methods was high (P < 0.001). PhCI increased with swallows for pharyngeal stimulation (P < 0.05) but remained stable for swallows with oral stimulation. PhCI differed between proximal and distal pharynx (P < 0.001). CONCLUSIONS: PhCI is a novel reliable metric capable of distinguishing (1) proximal and distal pharyngeal activity, (2) effects of oral and pharyngeal stimulation, and (3) effects of prolonged stimulation. Changes in pharyngeal contractility with maturation, disease, and therapies can be examined with PhCI.