The effects of parenteral fish oil on neurodevelopment in preterm infants: A narrative review.

OBJECTIVE: This narrative review aimed to summarize studies assessing the effects of parenteral fish oil on neurodevelopment in preterm infants. METHODS: PubMed was searched (July 1985 to October 2023). We reviewed randomized controlled trials, and observational studies assessing intravenous lipid emulsion with fish oil in preterm infants (born less than 37 weeks' gestation), that reported long-term neurodevelopmental outcomes. RESULTS: We identified four publications relating to three randomized controlled trials in addition to four cohort studies. Study designs and outcomes were heterogenous and precluded meta-analyses. Results of trials were null for a selection of neurodevelopmental outcomes, however possible benefits of parenteral fish oil supplementation for neurodevelopment was reported in three cohort studies. Certainty of the evidence is hindered by methodological limitations of available trials and observational studies. CONCLUSIONS: Further research is required to firmly establish the effects of parenteral fish oil on preterm neurodevelopment.

Subgroup analyses of a randomized trial of DHA supplementation for infants born preterm with assessments of cognitive development up to 7-years of age: What happens in infants born <29 weeks' gestation?

A recent trial showed that high-dose docosahexaenoic acid (high-DHA) supplementation of infants born <29 weeks' gestation improves intelligence quotient (IQ) at five years' corrected age. However, this finding has not been detected by other trials of DHA, which either did not measure IQ or included more mature infants. We analyzed the subgroup of 204 infants born <29 weeks' from our earlier randomized trial of high-DHA (∼1 % total fatty acids) or standard-DHA (∼ 0.3 % total fatty acids). Participants were assessed for cognition at 18 months, and IQ and behavior at seven years' corrected age. No group differences were detected for mean cognitive, IQ or behavior scores. At 18 months, 18.8 % of children in the high-DHA group had a cognitive score <85, compared with 31.1 % of children in the standard-DHA group, but at seven years there was no difference. Although an underpowered post-hoc subgroup analysis, this study provides limited support to recommendations that infants born <29 weeks' gestation require supplemental DHA.

ISSFAL statement number 7 - Omega-3 fatty acids during pregnancy to reduce preterm birth.

Globally, preterm birth is the leading cause of death in children under the age of 5 years and survivors may suffer life-long consequences. Following many years of investigation, there is strong evidence that a proportion of preterm births can be prevented by increasing maternal dietary omega-3 long chain polyunsaturated fatty acid (LCPUFA) intake during pregnancy. This Statement provides a synthesis of contemporary evidence on the role of omega-3 LCPUFA on prevention of preterm birth and is designed to provide fatty acid-specific knowledge and guidance for medical practitioners, midwives, health services, professional bodies and policy makers to consider for their contextual situations. The evidence synthesis, which underpins this statement, is based on the 2018 Cochrane systematic review with supplemental evidence from RCTs completed since that time as well as other systematic reviews. Heterogeneity between studies was explored to understand how the effect of omega-3 supplementation may vary in different population groups and by dose and type of omega-3 supplementation. Most trials were conducted in upper-middle or high-income countries and the evidence are most applicable in those settings. The evidence synthesis confirmed that omega-3 LCPUFA, particularly docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have an important role to play in determining gestational length in singleton pregnancies. Adequate intake of omega-3 LCPUFA in early pregnancy, consistent with existing nutritional guidelines, is associated with a lower risk of preterm and early preterm births for women with singleton pregnancies. Therefore, women with adequate omega-3 intakes in early pregnancy should maintain these intakes. Women who are low in omega-3 fatty acids will benefit most from omega-3 LCPUFA supplementation to reduce their risk of early birth. In such cases supplementation with a total of about 1000 mg of DHA plus EPA is effective at reducing risk of early birth, preferably with supplementation commencing before 20 weeks' gestation.

The epidemiology of moral bioenhancement.

In their 2008 paper, Persson and Savulescu suggest that for moral bioenhancement (MBE) to be effective at eliminating the danger of 'ultimate harm' the intervention would need to be compulsory. This is because those most in need of MBE would be least likely to undergo the intervention voluntarily. By drawing on concepts and theories from epidemiology, this paper will suggest that MBE may not need to be universal and compulsory to be effective at significantly improving the collective moral standing of a human populace and reducing the threat of ultimate harm. It will identify similarities between the mechanisms that allow biological contagions (such as a virus) and behaviours (such as those concerned with ethical and unethical actions) to develop, spread, and be reinforced within a population. It will then go onto suggest that, just as with the epidemiological principle of herd immunity, if enough people underwent MBE to reach a minimum threshold then the incidence and spread of immoral behaviours could be significantly reduced, even in those who have not received MBE.

Effect of omega-3 lcpufa supplementation on maternal fatty acid and oxylipin concentrations during pregnancy.

INTRODUCTION: Omega-3 long chain polyunsaturated fatty acids (LCPUFA) have been associated with a reduction in risk for preterm birth. However, there is limited understanding of how fatty acids and their bioactive derivatives (oxylipins) change over the course of pregnancy. Here we document the changes in concentration of fatty acids and oxylipins during pregnancy and how fatty acid status and oxylipin concentrations are affected by supplementation with omega-3 LCPUFA. We also investigate the degree to which fatty acid and oxylipin changes across pregnancy are influenced by baseline omega-3 status. MATERIALS AND METHODS: We profiled the fatty acids in all lipids in dried blood spots (total blood fatty acids) by gas chromatography and free (unesterified) fatty acids and their associated oxylipins in separate dried blood spot samples by LC-MS-MS collected from a random sample of 1263 women with a singleton pregnancy who participated in the ORIP (Omega-3 fats to Reduce the Incidence of Prematurity) trial. ORIP is a double-blind, randomized controlled trial involving 5544 participants and designed to determine the effect of supplementing the diets of pregnant women with omega-3 LCPUFA on the incidence of early preterm birth. Maternal whole blood finger prick samples were collected at baseline (~14 weeks gestation) and at completion of the study intervention period (34 weeks gestation). RESULTS: The concentration of most total and free polyunsaturated fatty acids and their associated oxylipins declined over the course of pregnancy. Omega-3 LCPUFA supplementation increased total DHA and 7-HDHA and mitigated the decline in free DHA, 4-HDHA and 14-HDHA. The intervention had minimal or no effect on free EPA, LA, AA and their associated oxylipins. Omega-3 LCPUFA supplementation in women with higher omega-3 status at baseline was associated with a significant increase in 7-HDHA and 4-HDHA between the treatment and control whereas there were no differences between groups in 7-HDHA and 4-HDHA in women with intermediate or lower baseline omega-3 status. CONCLUSION: Our data suggest a differential response with or without omega-3 supplementation for DHA and DHA-derived oxylipins, which may have an important role to play in modulating pregnancy duration. Further work is needed to understand their role, which may allow us to better tailor omega-3 supplementation for preterm birth prevention.

Clinical and advanced neurophysiology in the prognostic and diagnostic evaluation of disorders of consciousness: review of an IFCN-endorsed expert group.

The analysis of spontaneous EEG activity and evoked potentialsis a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). Thepast few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury,opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of bothconsolidated and investigational electrophysiological techniquesfor the prognostic and diagnostic assessment of DoC.We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats.The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation.

Omega-3 fatty acid supplementation in pregnancy-baseline omega-3 status and early preterm birth: exploratory analysis of a randomised controlled trial.

OBJECTIVE: To identify a polyunsaturated fatty acid (PUFA) biomarker able to detect which women with singleton pregnancies are most likely to benefit from omega-3 supplementation to reduce their risk of early preterm birth. DESIGN: Exploratory analysis of a randomised controlled trial. SETTING: Six Australian hospitals. POPULATION: Women with a singleton pregnancy enrolled in the ORIP trial. METHODS: Using maternal capillary whole blood collected ~14 weeks' gestation, the fatty acids in total blood lipids were quantified using gas chromatography. Interaction tests examined whether baseline PUFA status modified the effect of omega-3 supplementation on birth outcomes. MAIN OUTCOME MEASURE: Early preterm birth (<34 weeks' gestation). RESULTS: A low total omega-3 PUFA status in early pregnancy was associated with a higher risk of early preterm birth. Among women with a total omega-3 status ≤4.1% of total fatty acids, omega-3 supplementation substantially reduced the risk of early preterm birth compared with control (0.73 versus 3.16%; relative risk = 0.23, 95% confidence interval [CI] 0.07-0.79). Conversely, women with higher total omega-3 status in early pregnancy were at lower risk of early preterm birth. Supplementing women with a baseline status above 4.9% increased early preterm birth (2.20 versus 0.97%; relative risk = 2.27, 95% CI 1.13-4.58). CONCLUSIONS: Women with singleton pregnancies and low total omega-3 PUFA status early in pregnancy have an increased risk of early preterm birth and are most likely to benefit from omega-3 supplementation to reduce this risk. Women with higher total omega-3 status are at lower risk and additional omega-3 supplementation may increase their risk. TWEETABLE ABSTRACT: Low total omega-3 fat status helps identify which women benefit from extra omega-3 to reduce early prematurity.

Modeling Epidemics in Seed Systems and Landscapes To Guide Management Strategies: The Case of Sweet Potato in Northern Uganda.

Seed systems are critical for deployment of improved varieties but also can serve as major conduits for the spread of seedborne pathogens. As in many other epidemic systems, epidemic risk in seed systems often depends on the structure of networks of trade, social interactions, and landscape connectivity. In a case study, we evaluated the structure of an informal sweet potato seed system in the Gulu region of northern Uganda for its vulnerability to the spread of emerging epidemics and its utility for disseminating improved varieties. Seed transaction data were collected by surveying vine sellers weekly during the 2014 growing season. We combined data from these observed seed transactions with estimated dispersal risk based on village-to-village proximity to create a multilayer network or "supranetwork." Both the inverse power law function and negative exponential function, common models for dispersal kernels, were evaluated in a sensitivity analysis/uncertainty quantification across a range of parameters chosen to represent spread based on proximity in the landscape. In a set of simulation experiments, we modeled the introduction of a novel pathogen and evaluated the influence of spread parameters on the selection of villages for surveillance and management. We found that the starting position in the network was critical for epidemic progress and final epidemic outcomes, largely driven by node out-degree. The efficacy of node centrality measures was evaluated for utility in identifying villages in the network to manage and limit disease spread. Node degree often performed as well as other, more complicated centrality measures for the networks where village-to-village spread was modeled by the inverse power law, whereas betweenness centrality was often more effective for negative exponential dispersal. This analysis framework can be applied to provide recommendations for a wide variety of seed systems.[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Amitriptyline prevents CPT-11-induced early-onset diarrhea and colonic apoptosis without reducing overall gastrointestinal damage in a rat model of mucositis.

PURPOSE: Gastrointestinal mucositis (GIM) is one of the most debilitating side effects of the chemotherapy agent, irinotecan hydrochloride (CPT-11). The toll-like receptor (TLR) pathway is a key mediator implicated in the pathophysiology underlying GIM. The tricyclic antidepressant amitriptyline has been shown to inhibit TLR2 and TLR4 activity in in vitro models. The aim of this study was therefore to investigate the effect of amitriptyline on the development of GIM following CPT-11. METHODS: Male albino Wistar rats were treated with either CPT-11 (125 mg/kg, i.p., n = 18), amitriptyline (20 mg/kg, n = 18), both agents (n = 18), or vehicle control (n = 18) and killed at 6, 48, or 96 h. Differences between groups in measurements of gastrointestinal toxicity (diarrhea and weight loss), mucosal injury (apoptosis and histopathology score), colonic expression of TLRs, and pro-inflammatory cytokines were determined. RESULTS: CPT-11-induced diarrhea and colonic apoptosis were inhibited by amitriptyline at 6 h. However, rats were not protected from weight loss or mucosal injury over the time course of CPT-11-induced GIM. Interleukin-1 beta transcript expression was significantly decreased with amitriptyline treatment at 6 h, although protein expression did not differ between groups. There was no change in TLR4 or TLR2 expression in any group. CONCLUSIONS: Prophylactic amitriptyline was able to inhibit early intestinal damage in this rat model of CPT-11-induced GIM, but exacerbated late-onset injury. These findings do not support use of amitriptyline as an approach for mitigation of GIM in this setting.

Dementia among Older Persons in Jamaica: Prevalence and Policy Implications / La demencia entre las personas de edad en Jamaica: prevalencia e implicaciones para la implementación de políticas

ABSTRACT Objective: To determine the prevalence of dementia and dementia types in Jamaica. Methods: An embedded case-control design was used to investigate dementia within the ageing population. Cases (Mini-Mental State Examination [MMSE] scores of < 20) and controls (MMSE scores of > 20) were evaluated using DSM-IVprotocol and magnetic resonance imaging. Prevalences (crude and age-adjusted) were calculated and distribution of dementia by type described. Results: Dementia prevalence was 5.9%. Alzheimer's pattern dementia accounted for 61.8% and vascular dementia 32.4%. However, vascular disease was prominent in 45.5% of the Alzheimer's cases. Female gender and increasing age were associated with higher rates of dementia. Dementia was 38 times more likely in participants with MMSE scores below 20. Conclusion: This first nationally representative study indicated that dementia rates in Jamaica were comparable with regional and global estimates. Regardless of the dementia type, vascular change was pervasive and suggested that synergistic efforts should be made to address underlying contributory factors. Cardiovascular and cerebrovascular risk reduction should be deliberately pursued as integral adjuncts to dementia risk reduction.

RESUMEN Objetivo: Determinar la prevalencia de los tipos de demencia y demencia en Jamaica. Métodos: Se utilizó un diseño de caso-control incrustado para investigar la demencia dentro de la población en proceso de envejecimiento. Los casos (puntuación < 20 en el Mini Examen del Estado Mental [MEEM]) y los controles (puntuación > 20 en el MEEM) fueron evaluados usando el protocolo DSM-IVy la imagen por resonancia magnética. Se calcularon prevalencias (crudas y ajustadas por edad) y se describió la distribución de la demencia por tipo. Resultados: La prevalencia de demencia fue de 5.9%. El Alzheimer representó el 61.8% y la demencia vascular 32.4%. Sin embargo, la enfermedad vascular fue prominente en el 45.5% de los casos de Alzheimer. El género femenino y la edad creciente se asociaron con tasas más altas de demencia. La demencia fue 38 veces más probable en los participantes con puntuaciones de MEEM por debajo de 20. Conclusión: Este primer estudio nacionalmente representativo indicó que las tasas de demencia en Jamaica eran comparables con los estimados regionales y globales. Independientemente del tipo de demencia, el cambio vascular fue generalizado y sugirió que se hicieran esfuerzos sinérgicos para abordar los factores contribuyentes subyacentes. Debe buscarse deliberadamente la reducción del riesgo cardiovascular y cerebrovascular como adjuntos integrantes de la reducción del riesgo de demencia.

Exposure to maternal cafeteria diets during the suckling period has greater effects on fat deposition and Sterol Regulatory Element Binding Protein-1c (SREBP-1c) gene expression in rodent offspring compared to exposure before birth.

BACKGROUND: While the adverse metabolic effects of exposure to obesogenic diets during both the prenatal and early postnatal period are well established, the relative impact of exposure during these separate developmental windows remains unclear. This study aimed to assess the relative contribution of exposure to a maternal cafeteria diet during pregnancy and lactation on body weight, fat mass and expression of lipogenic and adipokine genes in the offspring. METHODS: Wistar rats were fed either a control chow (Control, n = 14) or obesogenic cafeteria diet (CAF, n = 12) during pregnancy and lactation. Pups were cross-fostered to another dam in either the same or different dietary group within 24 h of birth. Body weight, body fat mass and expression of lipogenic and adipokine genes in subcutaneous and visceral adipose tissues were determined in offspring at weaning and 3 weeks post-weaning. RESULTS: Offspring suckled by CAF dams had a lower body weight (P < 0.05), but ~ 2-fold higher percentage body fat at weaning than offspring suckled by Control dams (P < 0.01), independent of whether they were born to a Control or CAF dam. At 6 weeks of age, after all offspring were weaned onto standard chow, males and females suckled by CAF dams remained lighter (P < 0.05) than offspring suckled by Control dams, but the percentage fat mass was no longer different between groups. Sterol Regulatory Element Binding Protein-1c (SREBP-1c) mRNA expression was ~ 25% lower in offspring suckled by cafeteria dams in males at weaning (P < 0.05) and in females at 6 weeks of age (P < 0.05). Exposure to a cafeteria diet during the suckling period alone also resulted in increased adipocyte Peroxisome Proliferator Activated Receptor-γ (PPAR-γ) mRNA expression in females, and adiponectin and leptin mRNA expression in both sexes at weaning. CONCLUSIONS: The findings from this study point to the critical role of the suckling period for deposition of adipose tissue in rodents, and the potential role of altered adipocyte gene expression in mediating these effects.

DNA methylation in blood from neonatal screening cards and the association with BMI and insulin sensitivity in early childhood.

BACKGROUND/OBJECTIVES: There is increasing evidence that metabolic diseases originate in early life, and epigenetic changes have been implicated as key drivers of this early life programming. This led to the hypothesis that epigenetic marks present at birth may predict an individual's future risk of obesity and type 2 diabetes. In this study, we assessed whether epigenetic marks in blood of newborn children were associated with body mass index (BMI) and insulin sensitivity later in childhood. SUBJECTS/METHODS: DNA methylation was measured in neonatal blood spot samples of 438 children using the Illumina Infinium 450 k BeadChip. Associations were assessed between DNA methylation at birth and BMI z-scores, body fat mass, fasting plasma glucose, insulin and homeostatic model assessment of insulin resistance (HOMA-IR) at age 5 years, as well as birth weight, maternal BMI and smoking status. RESULTS: No individual methylation sites at birth were associated with obesity or insulin sensitivity measures at 5 years. DNA methylation in 69 genomic regions at birth was associated with BMI z-scores at age 5 years, and in 63 regions with HOMA-IR. The methylation changes were generally small (<5%), except for a region near the non-coding RNA nc886 (VTRNA2-1) where a clear link between methylation status at birth and BMI in childhood was observed (P=0.001). Associations were also found between DNA methylation, maternal smoking and birth weight. CONCLUSIONS: We identified a number of DNA methylation regions at birth that were associated with obesity or insulin sensitivity measurements in childhood. These findings support the mounting evidence on the role of epigenetics in programming of metabolic health. Whether many of these small changes in DNA methylation are causally related to the health outcomes, and of clinical relevance, remains to be determined, but the nc886 region represents a promising obesity risk marker that warrants further investigation.

The effect of maternal DHA supplementation on body fat mass in children at 7 years: follow-up of the DOMInO randomized controlled trial.

BACKGROUND: Animal studies have suggested that an increased supply of omega-3 long chain polyunsaturated fatty acids (LCPUFA), in particular docosahexaenoic acid (DHA), during the perinatal period can prevent later excess body fat mass. However, previous human studies have produced inconsistent findings, and few have assessed potential effects beyond 6 years of age. OBJECTIVE: To evaluate the effect of supplementing women in the second half of pregnancy with omega-3 LCPUFA, chiefly as DHA, on the percentage body fat of children at 7 years of age, as assessed by two methods: air displacement plethysmography (BOD POD) and bioelectrical impedance spectroscopy (BIS). DESIGN: A time-restricted follow up at 7 years of age of children born to mothers enrolled in DOMInO (DHA to Optimise Maternal Infant Outcome) randomized controlled trial, in which women took either high-DHA tuna oil (800mg/day DHA) or placebo capsules from 20 weeks' gestation to delivery, at Adelaide-based centers. Primary outcomes were the percentage body fat at 7 years of age as assessed by both BOD POD and BIS. Weight, height, waist/hip circumferences and BMI were also recorded. RESULTS: A total of 252 DOMInO children (n=135 males, n=117 females) completed the follow up study. There were no differences between the DHA and placebo groups in percentage body fat as assessed by either BOD POD [adjusted mean difference: -0.35, 95% CI: -1.46, 2.16; P=0.71] or BIS [adjusted mean difference: 0.64, 95% CI: -0.99, 2.27; P=0.44]. BMI z-scores were also similar between groups [adjusted mean difference: 0.18, 95% CI: -0.10, 0.45; P=0.21]. There were also no differences in height, weight or waist and hip circumference between the DHA and placebo groups at 7 years of age. CONCLUSION: DHA supplementation in the second half of pregnancy has no effect on childhood growth or fat mass at 7 years of age, supporting findings from follow ups of the DOMInO children at 3 and 5 years.

Longitudinal development of initial, chronic and mucoid Pseudomonas aeruginosa infection in young children with cystic fibrosis.

BACKGROUND: While the emergence of chronic and mucoid Pseudomonas aeruginosa (Pa) infection are both associated with poorer outcomes among CF patients, their relationship is poorly understood. We examined the longitudinal relationship of incident, chronic and mucoid Pa in a contemporary, young CF cohort in the current era of Pa eradication therapy. METHODS: This retrospective cohort was comprised of patients in the U.S. CF Foundation Patient Registry born 2006-2015, diagnosed before age 2, and with at least 3 respiratory cultures annually. Incidence and age-specific prevalence of Pa infection stages (initial and chronic [≥ 3Pa+cultures in prior year]) and of mucoid Pa were summarized. Transition times and the interaction between Pa stage and acquisition of mucoid Pa were examined via Cox models. RESULTS: Among the 5592 CF patients in the cohort followed to a mean age of 5.5years, 64% (n=3580) acquired Pa. Of those, 13% (n=455) developed chronic Pa and 17% (n=594) cultured mucoid Pa. Among those with mucoid Pa, 36% (211/594) had it on their first recorded Pa+culture, while mucoid Pa emerged at or after entering the chronic stage in 12% (73/594). Mucoidy was associated with significantly increased risk of transition to chronic Pa infection (HR=2.59, 95% CI 2.11, 3.19). CONCLUSIONS: Two-thirds of early-diagnosed young children with CF acquired Pa during a median 5.6years of follow up, among whom 13% developed chronic Pa and 17% acquired mucoid Pa. Contrary to our hypothesis, 87% of young children who developed mucoid Pa did so before becoming chronically infected.

Postnatal Identification of Zika Virus Peptides from Saliva.

We explored the potential to diagnose Zika virus (ZIKV) infection by analyzing peptides in saliva during a convalescent phase of infection, long after resolution of acute disease. A 25-y-old woman clinically diagnosed with Zika fever in the first trimester was enrolled with her dizygotic twins for a 3-mo postnatal sample of saliva (9-mo after maternal infection). The female baby (A) had microcephaly while the male baby (B) was born healthy. Peptidomic analysis was completed by mass spectrometry (MS/MS), and ZIKV peptides were identified using the National Institutes of Health Zika Virus Resource database, then aligned and mapped to the ZIKV polyprotein to determine proteome coverage and phylogenetic studies. A total of 423 (mother), 607 (baby A), and 183 (baby B) unique ZIKV peptides were identified in saliva by MS/MS, providing a coverage of 67%, 84%, and 45%, respectively, of the entire ZIKV polyprotein (>3,400 amino acids). All peptides were aligned to other flaviviruses that are circulating in Brazil (dengue and yellow fever) to discard false-positive matches. Nine peptides identified were highly conserved to dengue virus. Alignment of a contiguous peptide sequence for mother/babies with the 74 ZIKV sequences suggested that the virus may have entered the oral cavity through the salivary glands, leading to an infection that persists into the postnatal period (vertical transmission). Furthermore, we identified 9 sequence variations that were unique to the baby with microcephaly (not found in the mother or the twin). This sequence information could provide a template for future neuropathogenic studies. A much larger sample size is required to determine whether sequence variation in the envelope protein significantly associates with microcephaly. Finally, from a public health perspective, it will be important to determine whether viral replication is still taking place after birth and whether the virus can be transmitted through salivary contact.

Rationalizing endpoints for prospective studies of pulmonary exacerbation treatment response in cystic fibrosis.

BACKGROUND: Given the variability in pulmonary exacerbation (PEx) management within and between Cystic Fibrosis (CF) Care Centers, it is possible that some approaches may be superior to others. A challenge with comparing different PEx management approaches is lack of a community consensus with respect to treatment-response metrics. In this analysis, we assess the feasibility of using different response metrics in prospective randomized studies comparing PEx treatment protocols. METHODS: Response parameters were compiled from the recent STOP (Standardized Treatment of PEx) feasibility study. Pulmonary function responses (recovery of best prior 6-month and 12-month FEV1% predicted and absolute and relative FEV1% predicted improvement from treatment initiation) and sign and symptom recovery from treatment initiation (measured by the Chronic Respiratory Infection Symptom Score [CRISS]) were studied as categorical and continuous variables. The proportion of patients retreated within 30days after the end of initial treatment was studied as a categorical variable. Sample sizes required to adequately power prospective 1:1 randomized superiority and non-inferiority studies employing candidate endpoints were explored. RESULTS: The most sensitive endpoint was mean change in CRISS from treatment initiation, followed by mean absolute FEV1% predicted change from initiation, with the two responses only modestly correlated (R2=.157; P<0.0001). Recovery of previous best FEV1 was a problematic endpoint due to missing data and a substantial proportion of patients beginning PEx treatment with FEV1 exceeding their previous best measures (12.1% >12-month best, 19.6% >6-month best). Although mean outcome measures deteriorated approximately 2-weeks post-treatment follow-up, the effect was non-uniform: 62.7% of patients experienced an FEV1 worsening versus 49.0% who experienced a CRISS worsening. CONCLUSIONS: Results from randomized prospective superiority and non-inferiority studies employing mean CRISS and FEV1 change from treatment initiation should prove compelling to the community. They will need to be large, but appear feasible.