Enhancing drug checking services for supply monitoring: perspectives on implementation in syringe service programs in the USA.

BACKGROUND: Shifts in the US drug supply, including the proliferation of synthetic opioids and emergence of xylazine, have contributed to the worsening toll of the overdose epidemic. Drug checking services offer a critical intervention to promote agency among people who use drugs (PWUD) to reduce overdose risk. Current drug checking methods can be enhanced to contribute to supply-level monitoring in the USA, overcoming the selection bias associated with existing supply monitoring efforts and informing public health interventions. METHODS: As a group of analytical chemists, public health researchers, evaluators, and harm reductionists, we used a semi-structured guide to facilitate discussion of four different approaches for syringe service programs (SSPs) to offer drug checking services for supply-level monitoring. Using thematic analysis, we identified four key principles that SSPs should consider when implementing drug checking programs. RESULTS: A number of analytical methods exist for drug checking to contribute to supply-level monitoring. While there is likely not a one-size-fits-all approach, SSPs should prioritize methods that can (1) provide immediate utility to PWUD, (2) integrate seamlessly into existing workflows, (3) balance individual- and population-level data needs, and (4) attend to legal concerns for implementation and dissemination. CONCLUSIONS: Enhancing drug checking methods for supply-level monitoring has the potential to detect emerging threats in the drug supply and reduce the toll of the worsening overdose epidemic.

Differential risks of syringe service program participants in Central Ohio: a latent class analysis.

BACKGROUND: Significant heterogeneity exists among people who use drugs (PWUD). We identify distinct profiles of syringe service program (SSP) clients to (a) evaluate differential risk factors across subgroups and (b) inform harm reduction programming. METHODS: Latent class analysis (LCA) was applied to identify subgroups of participants (N = 3418) in a SSP in Columbus, Ohio, from 2019 to 2021. Demographics (age, sex, race/ethnicity, sexual orientation, housing status) and drug use characteristics (substance[s] used, syringe gauge, needle length, using alone, mixing drugs, sharing supplies, reducing use, self-reported perceptions on the impact of use, and treatment/support resources) were used as indicators to define latent classes. A five-class LCA model was developed, and logistic regression was then employed to compare risk factors at program initiation and at follow-up visits between latent classes. RESULTS: Five latent classes were identified: (1) heterosexual males using opioids/stimulants with housing instability and limited resources for treatment/support (16.1%), (2) heterosexual individuals using opioids with stable housing and resources for treatment/support (33.1%), (3) individuals using methamphetamine (12.4%), (4) young white individuals using opioids/methamphetamine (20.5%), and (5) females using opioids/cocaine (17.9%). Class 2 served as the reference group for logistic regression models, and at the time of entry, class 1 was more likely to report history of substance use treatment, overdose, HCV, sharing supplies, and mixing drugs, with persistently higher odds of sharing supplies and mixing drugs at follow-up. Class 3 was more likely to report history of overdose, sharing supplies, and mixing drugs, but outcomes at follow-up were comparable. Class 4 was the least likely to report history of overdose, HCV, and mixing drugs, but the most likely to report HIV. Class 5 was more likely to report history of substance use treatment, overdose, HCV, sharing supplies, and mixing drugs at entry, and higher reports of accessing substance use treatment and testing positive for HCV persisted at follow-up. CONCLUSIONS: Considerable heterogeneity exists among PWUD, leading to differential risk factors that may persist throughout engagement in harm reduction services. LCA can identify distinct profiles of PWUD accessing services to tailor interventions that address risks, improve outcomes, and mitigate disparities.

Characterization of Esophageal and Sphincter Reflexes across Maturation in Dysphagic Infants with Oral Feeding Success vs Infants requiring Gastrostomy.

To test the hypothesis that esophageal and sphincteric sensory-motor reflexes are distinct across maturation in infants with dysphagia receiving gastrostomy-tube (G-tube). This is a retrospective review of 29 dysphagic infants (N = 15 study requiring gastrostomy, N = 14 age matched control achieving oral feeds) that underwent longitudinal pharyngeal-esophageal manometry at 42.3 (37-50.2) weeks postmenstrual age (PMA) and 48.9 (43.3-57.9) weeks PMA. Graded stimuli (0.1-5 mL) of varying media (air, water, and apple juice) tested esophageal peristaltic reflex, upper esophageal sphincter contractile reflex (UESCR), and lower esophageal sphincter relaxation reflex (LESRR). Comparisons were performed between study and controls and across maturation (time-1 vs time-2). Data represented as mean ± SE or OR (95% CI). Across maturation (time-1 vs time-2): Study infants did not exhibit significant differences across in peristaltic, UES, or LES reflexes (all p > 0.05). In contrast, controls exhibited increased UES resting pressure (13 ± 3 vs 17 ± 3 mmHg, p = 0.001), LES resting pressure (22 ± 3 vs 25 ± 3 mmHg, p < 0.009), LES nadir pressure (0.5 ± 1 vs 4.3 ± 1 mmHg, p = 0.001), and esophago-deglutition responses [2.5 (1.23-4.88), p = 0.04], and decreased secondary peristalsis [0.44 (0.31-0.61), p = 0.001], UESCR [0.4 (0.25-0.65), p = 0.001], LESRR [0.4 (0.24-0.75), p = 0.01], and symptoms [0.6 (0.45-0.83), p = 0.005]. Among infants with dysphagia, esophageal provocation induced peristaltic reflex, UESCR, and LESRR advance with longitudinal maturation when infants are oral-fed successfully, but not in those who received gastrostomy. Underlying mechanisms may be related to esophageal sensitivity, afferent or efferent transmission, and coordination of upstream excitation and downstream inhibition, which can be potential therapeutic targets for improving feeding capabilities after gastrostomy placement in infants with dysphagia.

Pharyngoesophageal motility reflex mechanisms in the human neonate: importance of integrative cross-systems physiology.

Swallowing is a critical function for survival and development in human neonates and requires cross-system coordination between neurological, airway, and digestive motility systems. Development of pharyngoesophageal motility is influenced by intra- and extrauterine development, pregnancy complications, and neonatal comorbidities. The primary role of these motility reflex mechanisms is to maintain aerodigestive homeostasis under basal and adaptive biological conditions including oral feeding, gastroesophageal reflux, and sleep. Failure may result in feeding difficulties, airway compromise, dysphagia, aspiration syndromes, and chronic eating difficulties requiring prolonged tube feeding. We review the integration of cross-systems physiology to describe the basis for physiological and pathophysiological neonatal aerodigestive functions.

Role of feeding strategy bundle with acid-suppressive therapy in infants with esophageal acid reflux exposure: a randomized controlled trial.

OBJECTIVE: To test the hypothesis that a feeding bundle concurrent with acid suppression is superior to acid suppression alone in improving gastroesophageal reflux disease (GERD) attributed-symptom scores and feeding outcomes in neonatal ICU infants. METHODS: Infants (N = 76) between 34 and 60 weeks' postmenstrual age with acid reflux index > 3% were randomly allocated to study (acid-suppressive therapy + feeding bundle) or conventional (acid-suppressive therapy only) arms for 4 weeks. Feeding bundle included: total fluid volume < 140 mL/kg/day, fed over 30 min in right lateral position, and supine postprandial position. Primary outcome was independent oral feeding and/or ≥6-point decrease in symptom score (I-GERQ-R). Secondary outcomes included growth (weight, length, head circumference), length of hospital stay (LOHS, days), airway (oxygen at discharge), and developmental (Bayley scores) milestones. RESULTS: Of 688 screened: 76 infants were randomized and used for the primary outcome as intent-to-treat, and secondary outcomes analyzed for 72 infants (N = 35 conventional, N = 37 study). For study vs. conventional groups, respectively: (a) 33% (95% CI, 19-49%) vs. 44% (95% CI, 28-62%), P = 0.28 achieved primary outcome success, and (b) secondary outcomes did not significantly differ (P > 0.05). CONCLUSIONS: Feeding strategy modifications concurrent with acid suppression are not superior to PPI alone in improving GERD symptoms or discharge feeding, short-term and long-term outcomes. IMPACT: Conservative feeding therapies are thought to modify GERD symptoms and its consequences. However, in this randomized controlled trial in convalescing neonatal ICU infants with GERD symptoms, when controlling for preterm or full-term birth and severity of esophageal acid reflux index, the effectiveness of acid suppression plus a feeding modification bundle (volume restriction, intra- and postprandial body positions, and prolonged feeding periods) vs. acid suppression alone, administered over a 4-week period was not superior in improving symptom scores or feeding outcomes. Restrictive feeding strategies are of no impact in modifying GERD symptoms or clinically meaningful outcomes. Further studies are needed to define true GERD and to identify effective therapies in modifying pathophysiology and outcomes. The improvement in symptoms and feeding outcomes over time irrespective of feeding modifications may suggest a maturational effect. This study justifies the use of placebo-controlled randomized clinical trial among NICU infants with objectively defined GERD.

Pharyngoesophageal and cardiorespiratory interactions: potential implications for premature infants at risk of clinically significant cardiorespiratory events.

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

Mechanisms of Aerodigestive Symptoms in Infants with Varying Acid Reflux Index Determined by Esophageal Manometry.

OBJECTIVE: To test whether symptom generation in infants is related to the severity of gastroesophageal reflux disease (GERD) symptoms as determined by the Acid Reflux Index (ARI), stimulus media, and stimulus volume during provocative esophageal manometry. STUDY DESIGN: Symptomatic neonates (n = 74) born at a median of 28.9 weeks gestation (range, 23.4-39.4 weeks) were studied at a median of 41.0 weeks (range, 34.6-48.0 weeks) postmenstrual age using 24-hour pH-impedance methods to determine ARI severity, followed by provocative esophageal manometry with graded mid-esophageal infusions (0.1-5.0 mL) of air, water, and apple juice. Peristaltic reflexes and symptom characteristics were compared among ARI severity categories using linear mixed models and generalized estimating equations. RESULTS: The effects of 2635 separate esophageal stimuli on reflexes and symptoms were analyzed. Peristaltic reflexes occurred in 1880 infusions (71%), and physical, cardiorespiratory, sensory symptoms were seen in 439 infusions (17%). Symptom prevalence did not differ across the ARI severity categories (ARI <3, 18%; ARI 3-7, 17%; ARI >7, 16%; P = 1.0). Symptom and peristaltic responses increased with incremental stimulus volumes (all media, P < .001). CONCLUSIONS: Symptoms and peristaltic reflexes are manifestations of the recruitment of several neurosensory and neuromotor pathways evoked by mid-esophageal infusions. ARI severity grade plays no role in symptom generation, indicating that GERD should not be diagnosed and severity should not be assigned based on symptoms alone. An increase in symptom occurrence was noted with increasing stimulus volumes, which provided increased activation of receptors, afferents, and efferents in evoking peristaltic clearance reflexes.

Differentiation of esophageal pH-impedance characteristics classified by the mucosal integrity marker in human neonates.

BACKGROUND: In adults, distal baseline impedance (BI) is a determinant of esophageal mucosal integrity with values <900 Ω indicating inflammation. Relationships between acid gastroesophageal reflux (GER) and BI in neonates are unclear. METHODS: NICU infants (N = 198, 30.4 ± 0.3 weeks gestation) were evaluated at 43 ± 0.4 weeks postmenstrual age using 24-h pH-impedance. Ten randomly selected 1-min windows during rest from the distal impedance channel (Z6) were averaged. Chi-square, t-tests, and ANOVA were used to compare pH-impedance and symptom characteristics by BI severity (BI < 900 Ω, BI 900-2000 Ω, BI > 2000 Ω). Regression analysis was used to identify potential contributing factors of BI. RESULTS: In BI < 900 Ω: (1) pH-impedance characteristics were increased (acid reflux event frequency, duration, and severity, all P < 0.05 vs. BI > 2000 Ω), and (2) positive symptom correlations were noted with bolus (73%) and acid events (55%). Significant predictors of BI included chronological age, acid reflux index, and BPD diagnosis (all P < 0.05). CONCLUSIONS: Low BI is associated with prolonged acid exposure, delayed clearance, and greater aerodigestive symptom prevalence, likely associated with inflammation and or increased mucosal permeability. BI > 2000 Ω likely involves little or no inflammation because acid exposure is minimal. Combination of SAP, pH-impedance metrics, and BI along with the clarification of dysmotility mechanisms provides the rationale for personalized anti-reflux therapies as needed.

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.

Maturation Modulates Pharyngeal-Stimulus Provoked Pharyngeal and Respiratory Rhythms in Human Infants.

Pharyngeal-provocation induced aerodigestive symptoms in infants remain an enigma. Sources of pharyngeal provocation can be anterograde as with feeding, and retrograde as in gastroesophageal reflux. We determined maturational and dose-response effects of targeted pharyngeal-stimulus on frequency, stability, and magnitude of pharyngeal and respiratory waveforms during multiple pharyngeal swallowing responses in preterm-born infants when they were of full-term postmenstrual age (PMA). Eighteen infants (11 male) were studied longitudinally at 39.8 ± 4.8 weeks PMA (time-1) and 44.1 ± 5.8 weeks PMA (time-2). Infants underwent concurrent pharyngo-esophageal manometry, respiratory inductance plethysmography, and nasal airflow thermistor methods to test sensory-motor interactions between the pharynx, esophagus, and airway. Linear mixed models were used and data presented as mean ± SEM or %. Overall, responses to 250 stimuli were analyzed. Of the multiple pharyngeal swallowing responses (n = 160), with maturation (a) deglutition apnea duration decreases (p < 0.01), (b) number of pharyngeal waveform peaks and duration decreases for initial responses (p < 0.01), and subsequent responses have lesser variation and greater stability (p < 0.01). With increment in stimulus volumes we noted (a) increased prevalence (%) of pharyngeal responses (p < 0.05), (b) increased number of pharyngeal peaks (p < 0.05), yet pharyngeal frequency (Hz), variability, and stability remain unaffected (p > 0.05), and (c) respiratory changes were unaffected (p > 0.05). Initial and subsequent pharyngeal responses and respiratory rhythm interactions become more distinct with maturation. Interval oromotor experiences and volume-dependent increase in adaptive responses may be contributory. These mechanisms may be important in modulating and restoring respiratory rhythm normalcy.

Effects of Esophageal Acidification on Troublesome Symptoms: An Approach to Characterize True Acid GERD in Dysphagic Neonates.

To quantify and compare maximal extent (height) of acid reflux events (AREs) on symptom generation in dysphagic neonates. Dysphagic neonates (N = 53), born at 30 ± 5.3 weeks gestation, underwent 24-hour pH-impedance study for the evaluation of troublesome symptoms purported to be due to gastroesophageal reflux disease (GERD). AREs (pH < 4 for >4 s) detected by impedance (Z) were categorized by maximal extent as refluxate reaching distal (Z6, Z5), middle (Z4, Z3), or proximal (Z2, Z1) impedance channels. AREs reaching the pH sensor only were categorized as distal. Symptom correlation (%, symptom index, symptom sensitivity index, and symptom associated probability) and temporal characteristics (clearance times) of AREs were analyzed using linear mixed and GEE models comparing height categories presented as mean ± SEM, median (IQR), and OR (95% CI). Of the 2003 AREs, 1) distal extent AREs (n = 1642) had increased frequency (p < 0.05), decreased ACT (p < 0.05), and decreased acidity (p < 0.05); 2) in middle and proximal AREs, acid clearance was longer than bolus clearance, (p < 0.01); and 3) the odds of having cardiorespiratory (cough or sneeze) symptoms are increased with proximal and middle AREs (p < 0.05). Most proximal ascent of AREs into middle or proximal esophagus likely activates protective aerodigestive reflexes (peristalsis) or vigilant states to facilitate bolus and chemical clearance. Heightened esophageal sensitivity, acid neutralization delays, or clearance mechanism delays may accentuate multi-systemic troublesome symptoms.

Effect of nasal noninvasive respiratory support methods on pharyngeal provocation-induced aerodigestive reflexes in infants.

The pharynx is a locus of provocation among infants with aerodigestive morbidities manifesting as dysphagia, life-threatening events, aspiration-pneumonia, atelectasis, and reflux, and such infants often receive nasal respiratory support. We determined the impact of different oxygen delivery methods on pharyngeal stimulation-induced aerodigestive reflexes [room air (RA), nasal cannula (NC), and nasal continuous positive airway pressure (nCPAP)] while hypothesizing that the sensory motor characteristics of putative reflexes are distinct. Thirty eight infants (28.0 ± 0.7 wk gestation) underwent pharyngoesophageal manometry and respiratory inductance plethysmography to determine the effects of graded pharyngeal stimuli (n = 271) on upper and lower esophageal sphincters (UES, LES), swallowing, and deglutition-apnea. Comparisons were made between NC (n = 19), nCPAP (n = 9), and RA (n = 10) groups. Importantly, NC or nCPAP (vs. RA) had: 1) delayed feeding milestones (P < 0.05), 2) increased pharyngeal waveform recruitment and duration, greater UES nadir pressure, decreased esophageal contraction duration, decreased distal esophageal contraction amplitude, and decreased completely propagated esophageal peristalsis (all P < 0.05), and 3) similarly developed UES contractile and LES relaxation reflexes (P > 0.05). We conclude that aerodigestive reflexes were similarly developed in infants using noninvasive respiratory support with adequate upper and lower aerodigestive protection. Increased concern for GERD is unfounded in this population. These infants may benefit from targeted oromotor feeding therapies and safe pharyngeal bolus transit to accelerate feeding milestones.

The physiologic coupling of sucking and swallowing coordination provides a unique process for neonatal survival.

AIM: Although the coordination of sucking and swallowing is critical for successful oral intake in neonates, the mechanisms that facilitate this coordination are not well understood. This investigation sought to clarify the mechanisms that facilitate this coordination, by comparing sucks that were coordinated with swallows and sucks that were completed in isolation. METHODS: Ten neonates with a median gestational age of 28.2 weeks, ranging from 27.0 to 35.0 weeks, were recruited from the neonatal nurseries at Nationwide Children's Hospital, Columbus, Ohio, USA. They were evaluated while bottle-feeding at term gestation for differences in characteristics between sucks that were coupled and not coupled with swallows. Suction was evaluated using an intra-oral pressure transducer, and swallows were identified using a micromanometry pharyngeal catheter. Linear mixed models were applied to distinguish sucking characteristics. RESULTS: Suction exhibited an antiphase relationship with the generation and release of positive pharyngeal pressure during the swallow. Coupled sucks had lower suction generation and release rates (p < 0.0001), lower suction amplitude (p = 0.004), longer suction duration (p < 0.0001) and higher milk ejection pressure (p < 0.0001). CONCLUSION: The coordination of unique sucking and swallowing movement patterns may be achieved by the infant adapting sucking kinematics around the lingual patterns that facilitate the pharyngeal swallow.

Mechanisms of cough provocation and cough resolution in neonates with bronchopulmonary dysplasia.

BACKGROUND: Cough and deglutition are protective mechanisms that defend against aspiration. We identified mechanisms associated with cough provocation as well as those associated with cough resolution in infants with bronchopulmonary dysplasia (BPD). METHODS: Manometry signatures of cough were recognized in 16 premature infants with BPD undergoing concurrent esophageal manometry, respiratory inductance plethysmography, and nasal air flow measurements. Pretussive and post-tussive pharyngo-esophageal motility changes were analyzed. Mechanisms associated with cough and mechanisms that restored respiratory and esophageal normalcy were analyzed. RESULTS: We analyzed 312 cough events during 88 cough clusters; 97% were associated with recognizable manometric patterns. Initial mechanisms related with coughing included nonpropagating swallow (59%), upper esophageal sphincter (UES) reflex contraction (18%), and lower esophageal sphincter (LES) relaxation (14%). UES and LES dysfunction was present in 69% of nonpropagating swallow-associated cough clusters. Mechanisms restoring post-tussive normalcy included primary peristalsis (84%), secondary peristalsis (8%), and none recognized (8%). UES contraction reflex was associated with cough clusters more frequently in infants on nasal continuous positive airway pressure (NCPAP) (OR = 9.13, 95% CI = 1.88-44.24). CONCLUSION: Cough clusters in infants with BPD had identifiable etiologies associated with esophageal events; common initial mechanisms were of upper aerodigestive origin, while common clearing mechanisms were peristaltic reflexes.

Esophageal reflexes modulate frontoparietal response in neonates: Novel application of concurrent NIRS and provocative esophageal manometry.

Central and peripheral neural regulation of swallowing and aerodigestive reflexes is unclear in human neonates. Functional near infrared spectroscopy (NIRS) is a noninvasive method to measure changes in oxyhemoglobin (HbO) and deoxyhemoglobin (HbD). Pharyngoesophageal manometry permits evaluation of aerodigestive reflexes. Modalities were combined to investigate feasibility and to test neonatal frontoparietal cortical changes during pharyngoesophageal (visceral) stimulation and/or swallowing. Ten neonates (45.6 ± 3.0 wk postmenstrual age, 4.1 ± 0.5 kg) underwent novel pharyngoesophageal manometry concurrent with NIRS. To examine esophagus-brain interactions, we analyzed cortical hemodynamic response (HDR) latency and durations during aerodigestive provocation and esophageal reflexes. Data are presented as means ± SE or percent. HDR rates were 8.84 times more likely with basal spontaneous deglutition compared with sham stimuli (P = 0.004). Of 182 visceral stimuli, 95% were analyzable for esophageal responses, 38% for HDR, and 36% for both. Of analyzable HDR (n = 70): 1) HbO concentration (µmol/l) baseline 1.5 ± 0.7 vs. 3.7 ± 0.7 poststimulus was significant (P = 0.02), 2) HbD concentration (µmol/l) between baseline 0.1 ± 0.4 vs. poststimulus -0.5 ± 0.4 was not significant (P = 0.73), and 3) hemispheric lateralization was 21% left only, 29% right only, and 50% bilateral. During concurrent esophageal and NIRS responses (n = 66): 1) peristaltic reflexes were present in 74% and HDR in 61% and 2) HDR was 4.75 times more likely with deglutition reflex vs. secondary peristaltic reflex (P = 0.016). Concurrent NIRS with visceral stimulation is feasible in neonates, and frontoparietal cortical activation is recognized. Deglutition contrasting with secondary peristalsis is related to cortical activation, thus implicating higher hierarchical aerodigestive protective functional neural networks.

Respiratory events in infants presenting with apparent life threatening events: is there an explanation from esophageal motility?

OBJECTIVE: To test the hypothesis that proximal aerodigestive clearance mechanisms mediated by pharyngoesophageal motility during spontaneous respiratory events (SREs) are distinct in infants with apparent life threatening events (ALTEs). STUDY DESIGN: Twenty infants (10 with proven ALTE, 10 healthy controls) had pharyngoesophageal manometry to investigate motility changes concurrent with respiratory events detected by respiratory inductance plethysmography and nasal thermistor methods. We measured changes in resting upper esophageal and lower esophageal sphincter pressures, esophageal peristalsis characteristics, and gastroesophageal reflux. Statistical analysis included mixed models; data presented as mean±SD, median (range), or percentage. RESULTS: Infants with ALTE (vs controls) had: (1) delays in restoring aerodigestive normalcy as indicated by more frequent (P=.03) and prolonged SREs (P<.01); (2) a lower magnitude of protective upper esophageal sphincter contractile reflexes (P=.01); (3) swallowing as the most frequent esophageal event associated with SREs (84%), with primary peristalsis as the most prominent aerodigestive clearance mechanism (64% vs 38%, P<.01); (4) a higher proportion of failed esophageal propagation (10% vs 0%, P=.02); and (5) more frequent mixed apneic mechanisms (P<.01) and more gasping breaths (P=.04). CONCLUSIONS: In infants with ALTE, prolonged SREs are associated with ineffective esophageal motility characterized by frequent primary peristalsis and significant propagation failure, thus suggestive of dysfunctional regulation of swallow-respiratory junction interactions. Hence, treatment should not target gastroesophageal reflux, but rather the proximal aerodigestive tract.

Association of Medicaid Reimbursement Policies with Provision of Long-Acting Reversible Contraception in the Postpartum Period, 2012-2018.

Background: To address reimbursement challenges associated with long-acting reversible contraception (LARC) in the postpartum period, state Medicaid programs have provided additional payments ("carve-outs"). Implementation has been heterogeneous, with states providing separate payments for the device only, procedure only, or both the device and procedure. Methods: Claims data were drawn from 210,994 deliveries in the United States between 2012 and 2018. Using generalized estimating equations, we assess the relationship between Medicaid carve-out policies and the likelihood of LARC placement at (1) 3 days postpartum, (2) 60 days postpartum, and (3) 1 year postpartum, in Medicaid and commercially insured populations. Results: Among Medicaid beneficiaries, the likelihood of receiving LARC was higher in states with any carve-out, compared with states without carve-outs, at 3 days (adjusted odds ratio [aOR] 1.49 [95% confidence interval: 1.33-1.67], p < 0.001), 60 days (aOR: 1.40 [95% CI: 1.35-1.46], p < 0.001), and 1 year postpartum (aOR: 1.15 [95% CI: 1.11-1.20], p < 0.001). Adjustments were made for geographic region, seasonality, and patient age. Heterogeneity was observed by carve-out type; device carve-outs were consistently associated with greater likelihood of postpartum LARC placement, compared with states with no carve-outs. Similar trends were observed among commercially insured patients. Conclusion: Findings support the effectiveness of Medicaid carve-outs on postpartum LARC provision, particularly for device carve-outs, which were associated with increased postpartum LARC placement at 3 days, 60 days, and 1 year postpartum. This outcome suggests that policies to address cost-related barriers associated with LARC devices may prove most useful in overcoming barriers to immediate postpartum LARC placement, with the overarching aim of promoting reproductive autonomy.

Policy Complexities in Financing First Episode Psychosis Services: Implementation Realities from a Home Rule State.

Over the past decade, significant investments have been made in coordinated specialty care (CSC) models for first episode psychosis (FEP), with the goal of promoting recovery and preventing disability. CSC programs have proliferated as a result, but financing challenges imperil their growth and sustainability. In this commentary, the authors discuss (1) entrenched and emergent challenges in behavioral health policy of consequence for CSC financing; (2) implementation realities in the home rule context of Ohio, where significant variability exists across counties; and (3) recommendations to improve both care quality and access for individuals with FEP. The authors aim to provoke careful thought about policy interventions to bridge science-to-service gaps, and in this way, advance behavioral health equity.

Proton pump inhibitor therapy may alter the sensory motor characteristics of pharyngoesophageal motility in infants with suspected GERD.

BACKGROUND: Acid reflux index (ARI) is a biomarker for gastroesophageal reflux disease (GERD). The effects of short-term proton pump inhibitor (PPI) therapy on pharyngoesophageal motility and clearance mechanisms in infants remain unknown. We hypothesized that pharyngoesophageal reflexes and response to PPI are distinct between infants with 3%-7% and >7% ARI. METHODS: Secondary analysis was performed from a subset of infants who participated in a randomized controlled trial (NCT: 02486263). Infants (N = 36, 29.9 ± 4.3 weeks gestation) underwent 4 weeks of PPI therapy, 1 week of washout, and longitudinal testing to assess: (a) clinical outcomes; (b) pH-impedance and symptom metrics including ARI, distal baseline impedance, clearance time, refluxate height, symptoms, I-GERQ-R scores, symptom association probability; (c) pharyngoesophageal motility reflexes and sensory motor characteristics. Comparisons were performed between infants with 3%-7% versus >7% ARI. KEY RESULTS: From the 36 hospitalized infants treated: Pharyngoesophageal reflex latencies were prolonged (p > 0.05) and duration in ARI 3%-7% group only (p = 0.01); GER frequency, proximal ascent and clearance increased (ARI 3%-7%); weight gain velocity, oral feeding success, and fine motor score decreased while length of hospital stays increased in the ARI >7% group despite the decrease in symptoms and I-GERQ-R scores. CONCLUSIONS & INFERENCES: Distinct changes in pharyngoesophageal sensory motor aspects of motility and reflex mechanisms exist after using PPI therapy in infants. Contributory factors may include the effects of maturation and aerodigestive comorbidities (GERD and BPD). Controlled studies incorporating placebo are needed to delineate the effects of PPI on causal and adaptive GERD mechanisms in infants with aerodigestive and feeding-related comorbidities.

Costs of Coordinated Specialty Care for First-Episode Psychosis: A Microcosting Analysis.

In this study, the authors measured and described the costs of coordinated specialty care (CSC) for first-episode psychosis in Ohio. A microcosting tool was used to estimate personnel and nonpersonnel costs of service delivery at seven CSC programs. Average annual cost per participant (N=511 participants) was estimated as $17,810 (95% CI=$9,141-$26,479). On average, 61% (95% CI=53%-69%) of annual program costs were nonbillable. Key cost drivers included facility costs, administrative tasks, and social services. Novel financing models may redress reimbursement gaps incurred by CSC programs.