SleepWell24, a Smartphone Application to Promote Adherence to Positive Airway Pressure Therapy: Feasibility and Acceptability in a Randomized Controlled Trial.

OBJECTIVE: To investigate the feasibility and acceptability of SleepWell24, a multicomponent, evidence-based smartphone application, to improve positive airway pressure therapy (PAP) adherence, among patients with obstructive sleep apnea (OSA) naive to PAP. METHODS: In a single-blind randomized controlled trial, SleepWell24, with a companion activity monitor was compared to usual care plus the activity monitor and its associated app. SleepWell24 provides objective feedback on PAP usage and sleep/physical activity patterns, and chronic disease management. Patients were recruited from two sleep medicine centers and followed over the first 60 days of PAP. Feasibility and acceptability were measured by recruitment/retention rates, app usage, differences in post-trial Treatment Evaluation Questionnaire (TEQ) scores, and patient interviews. Exploratory, intent-to-treat logistic and linear mixed models estimated PAP adherence and clinical outcomes. RESULTS: Of 103 eligible participants, 87 were enrolled (SleepWell24 n = 40, control n = 47; mean 57.6y [SD = 12.3], 44.8% female). Retention was ≥95% across arms. There were no significant differences in TEQ scores. SleepWell24 participants engaged with the app on 62.9% of trial days. PAP use was high across both arms (SleepWell24 vs. Control: mean hours 5.98 vs. 5.86). There were no differences in PAP adherence or clinical outcomes. CONCLUSIONS: SleepWell24 was feasible and acceptable among PAP-naive patients with OSA. CLINICAL TRIAL REGISTRATION: NCT03156283https://www.clinicaltrials.gov/study/NCT03156283.

History of obstructive sleep apnea associated with incident cognitive impairment in white but not black individuals in a US national cohort study.

BACKGROUND: We sought to determine if risk for obstructive sleep apnea (OSA), a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals. METHODS: To determine whether the risk for OSA, a history of OSA, and/or treatment of OSA has a different association with incident cognitive impairment or cognitive decline in Black individuals and White individuals; data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) was used. Participants that completed the sleep questionnaire module, had baseline cognitive assessment, and at least one cognitive assessment during follow-up were included. Risk of OSA was determined based on Berlin Sleep Questionnaire. History of sleep apnea was determined based on structured interview questions. Optimally treated OSA was defined as treated sleep apnea as at least 4 h of continuous positive airway pressure use per night for ≥5 nights per week. RESULTS: In 19,017 participants stratified by race, White participants with history of OSA were 1.62 times more likely to have incident cognitive impairment compared to White participants without history of OSA after adjusting for demographic characteristics, history, and lifestyle factors (OR = 1.62, 95% CI = 1.05-2.50, p-value = 0.03). This relationship was not seen in Black participants (OR = 0.92, 95% CI = 0.60-1.43, p-value = 0.72). DISCUSSION: A previous diagnosis of OSA is associated with incident cognitive impairment in White Americans but not Black Americans. Further investigations are required to determine the mechanism for this difference.

Isolation, characterization, and experimental infection of Streptococcus gallolyticus subspecies pasteurianus from commercial turkeys with acute septicemia: a pilot study.

Streptococcus gallolyticus (SG) is a Gram-positive cocci found as commensal gut flora in animals and humans. SG has emerged as a cause of disease in young poults between 1 and 3 wk of age. SG is associated with septicemia resulting in acute mortality with no premonitory signs in turkeys. Three SG isolates were obtained from clinical field cases of acute septicemia of commercial turkeys and used in three independent experiments. In Experiment 1, embryos were inoculated 25 d of embryogenesis with varying concentrations of SG1, SG2, or SG3. In Experiment 2, day of hatch, poults were inoculated with varying concentrations using different routes of administration of SG1, SG2, or SG3. In Experiment 3, day of hatch, poults were inoculated with only isolate SG1 using different paths. Poults were randomly selected for necropsy on d 8 and d 15 and sampled to collect spleen, heart, and liver for SG on d 21, the remaining poults were necropsied and cultured. Samples were plated on Columbia nalidixic acid and colistin agar (CNA) (40°C, 18-24 h). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed suspect colonies. Data were analyzed using the chi-square test of independence, testing all possible combinations to determine significance (P < 0.05). Weight data were subjected to ANOVA using JMP with significance (P < 0.05). No differences were found in BW or BWG on d 0, 8, 15, or 22. Splenomegaly, focal heart necrosis, and pericarditis were observed in all groups in experiments 1 through 3. In Experiment 3, only airsacculitis was observed in a negative control in separate isolation (P > 0.05). On d 21 of Experiment 3, increased (P < 0.05) recovery of SG from spleens were observed in co-housed negative controls, as well as poults challenged by oral gavage (P > 0.05 for d 7 and d 14). These results confirm numerous previous studies indicating that SG subsp. pasteurianus is a primary infectious microorganism that causes septicemia in young poults.

Evaluation of the impact of formaldehyde fumigation during the hatching phase on contamination in the hatch cabinet and early performance in broiler chickens.

Commercial hatch cabinet environments promote replication of microorganisms. These pathogenic or apathogenic microorganisms may serve as pioneer colonizers of the gastrointestinal tract (GIT) of poultry. Some of these pioneer colonizers, such as Escherichia coli and Enterococcus spp., are opportunistic pathogens that lead to reduced performance in commercial poultry. Effective hatchery sanitation is imperative to limit contamination of naïve neonatal chicks and poults. Formaldehyde fumigation has been traditionally used to reduce the pathogen load in commercial hatch cabinets. To investigate potential alternatives to formaldehyde fumigation, models to mimic the microbial bloom in a laboratory setting must be utilized. The purpose of the present study was to evaluate the impact of a multispecies environmental challenge model (PM challenge) with and without formaldehyde fumigation during the hatching phase on early performance in broiler chicks. Three experiments were conducted to evaluate microbial contamination in the hatch cabinet environment (air samples, fluff samples), enteric colonization at day-of-hatch (DOH), and 7-day performance. In all experiments, significantly (P < 0.05) more gram-negative bacteria were recovered from the GIT at DOH in the PM challenge control group as compared to the nonchallenged control (NC) group and the formaldehyde-treated group (PM + F). There were no statistical differences in 7-day body weight gain or feed conversion ratio between the PM challenge control group, the NC group or the PM + F group. These data suggest this model could be utilized to evaluate alternatives to formaldehyde fumigation for controlling the microbial load during the hatching phase in a laboratory setting.

Importance of Accounting for Regional Differences in Modifiable Risk Factors for Alzheimer's Disease and Related Dementias: The Case for Tailored Interventions.

BACKGROUND: We recently estimated that 36.9% of Alzheimer's disease and related dementias (ADRD) cases in the US may be attributable to modifiable risk factors, but it is not known whether national estimates generalize to specific states or regions. OBJECTIVE: To compare national estimates of modifiable risk factors of ADRD to California, overall and by sex and race/ethnicity, and to estimate number of cases potentially preventable by reducing the prevalence of key risk factors by 25%. METHODS: Adults ≥18 years who participated in the Behavioral Risk Factor Surveillance Survey in California (n = 9,836) and the US (n = 378,615). We calculated population attributable risks (PARs) for eight risk factors (physical inactivity, current smoking, depression, low education, diabetes mellitus, midlife obesity, midlife hypertension, and hearing loss) and compared estimates in California and the U.S. RESULTS: In California, overall, 28.9% of ADRD cases were potentially attributable to the combination of risk factors, compared to 36.9% in the U.S. The top three risk factors were the same in California and the U.S., although their relative importance differed (low education [CA:14.9%; U.S.:11.7% ], midlife obesity [CA:14.9%; U.S.:17.7% ], and physical inactivity [CA:10.3%; U.S.:11.8% ]). The number of ADRD cases attributable to the combined risk factors was 199,246 in California and 2,287,683 in the U.S. If the combined risk factors were reduced by 25%, we could potentially prevent more than 40,000 cases in California and 445,000 cases in the U.S. CONCLUSION: Our findings highlight the importance of examining risk factors of ADRD regionally, and within sex and race/ethnic groups to tailor dementia risk reduction strategies.

Risk Factors Associated With Alzheimer Disease and Related Dementias by Sex and Race and Ethnicity in the US.

Importance: Previous estimates suggested that 1 in 3 cases of Alzheimer disease and related dementia (ADRDs) in the US are associated with modifiable risk factors, the most prominent being physical inactivity, depression, and smoking. However, these estimates do not account for changes in risk factor prevalence over the past decade and do not consider potential differences by sex or race and ethnicity. Objective: To update estimates of the proportion of ADRDs in the US that are associated with modifiable risk factors and to assess for differences by sex and race and ethnicity. Design, Setting, and Participants: For this cross-sectional study, risk factor prevalence and communality were obtained from the nationally representative US Behavioral Risk Factor Surveillance Survey data from January 2018 to December 2018, and relative risks for each risk factor were extracted from meta-analyses. Data were analyzed from December 2020 to August 2021. Respondents included 378 615 noninstitutionalized adults older than 18 years. The number before exclusion was 402 410. Approximately 23 795 (~6%) had missing values on at least 1 of the variables of interest. Exposures: Physical inactivity, current smoking, depression, low education, diabetes, midlife obesity, midlife hypertension, and hearing loss. Main Outcomes and Measures: Individual and combined population-attributable risks (PARs) associated with ADRDs, accounting for nonindependence between risk factors. Results: Among 378 615 individuals, 171 161 (weighted 48.7%) were male, and 134 693 (weighted 21.1%) were 65 years and older. Race and ethnicity data were self-reported and defined by the US Behavioral Risk Factor Surveillance System Data; 6671 participants (weighted 0.9%) were American Indian and Alaska Native, 8043 (weighted 5.1%) were Asian, 29 956 (weighted 11.7%) were Black, 28 042 (weighted 16.0%) were Hispanic (any race), and 294 394 (weighted 64.3%) were White. Approximately 1 in 3 of ADRD cases (36.9%) in the US were associated with 8 modifiable risk factors, the most prominent of which were midlife obesity (17.7%; 95% CI, 17.5-18.0), physical inactivity (11.8%; 95% CI, 11.7-11.9), and low educational attainment (11.7%; 95% CI, 11.5-12.0). Combined PARs were higher in men (35.9%) than women (30.1%) and differed by race and ethnicity: American Indian and Alaska Native individuals, 39%; Asian individuals, 16%; Black individuals, 40%; Hispanic individuals (any race), 34%; and White individuals, 29%. The most prominent modifiable risk factors regardless of sex were midlife obesity for American Indian and Alaska Native individuals, Black individuals, and White individuals; low education for Hispanic individuals; and physical inactivity for Asian individuals. Conclusions and Relevance: The findings suggest that risk factors associated with ADRDs have changed over the past decade and differ based on sex and race and ethnicity. Alzheimer risk reduction strategies may be more effective if they target higher-risk groups and consider current risk factor profiles.

Development of an environmental contamination model to simulate the microbial bloom that occurs in commercial hatch cabinets.

Microbial blooms that emerge in commercial hatch cabinets consist of apathogenic and pathogenic microorganisms, including Escherichia coli, Enterococcus faecalis, and Aspergillus fumigatus. Objectives of the present study included the development of a multipathogen contamination model to mimic commercial conditions and optimization of sampling methods to quantify bacterial or fungal presence within the hatch cabinet. The pathogen challenge mix (PM) was recreated from select bacterial or fungal isolates recovered from an egg homogenate (EH) derived from the contents of infertile eggs and late embryonic mortalities. Isolates selected for PM included Enterococcus faecalis (∼108 CFU/egg), Staphylococcus aureus (∼107 CFU/egg), Staphylococcus chromogenes (∼107 CFU/egg), Aspergillus fumigatus (∼106 spores/egg), and 2 Escherichia coli (∼108 CFU/egg) isolates. Challenge (100 µL of PM or EH) was administered using a sterile loop to a 28 mm area on the blunt end of the eggshell at day 19 of embryogenesis (DOE). In 3 experiments, microbiological data were collected from environmental hatcher samples (open-agar plate method), fluff samples, postmortem whole-body chick rinse samples, and gastrointestinal tract (GIT) samples to evaluate select bacteria and fungi circulating within the hatch cabinet and colonization of GIT. Cumulative bacterial and fungal recovery from the PM hatching environment from DOE20 to hatch was higher than the nonchallenged group (NC) and EH group at ∼860 and ∼1,730 CFU, respectively. Bacterial recovery from GIT, fluff, and chick rinse samples were similar for the PM and EH group in Exp. 1. However, Aspergillus fumigatus recovery from fluff and chick rinse samples for the PM group was significantly (P < 0.001) higher than the NC and EH group. In Exp. 2 and 3, PM challenge significantly (P < 0.05) increased Gram-negative bacterial recovery from the GIT, fluff and chick rinse samples compared to both the NC and EH group. These data suggest this innovative multispecies environmental contamination model using PM could be utilized to evaluate strategies to mitigate microbial contamination in commercial hatch cabinets in a laboratory setting.

Aerobic physical activity to improve memory and executive function in sedentary adults without cognitive impairment: A systematic review and meta-analysis.

The worldwide population of adults ages 50 and older continues to increase and is projected to reach over 2.3 billion by 2030. Aging is the biggest risk factor for cognitive impairment and dementia. Aerobic physical activity may improve cognitive functioning, thus delaying aging-related cognitive decline. The purpose of this review was to examine the effect of aerobic physical activity on memory and executive function in sedentary adults with no known cognitive impairment. PubMed, CINAHL, Psycinfo, and Cochrane Library databases were systematically searched for peer-reviewed articles up to July 2019. Randomized controlled trials of sedentary adults, aged 50 and older, that compared an aerobic physical activity intervention to either no treatment or alternative active comparator and reported outcome measures of memory and/or executive function were included. A random effects meta-analysis was performed to examine the separate effect sizes for memory and executive function. Nine studies met inclusion criteria and contributed either memory and/or executive function effect sizes (n = 547). Results from the random effects meta-analysis suggested, by post-intervention, a large effect size for the aerobic physical activity interventions on memory (g = 0.80, 95%CI: 0.14-1.47; n = 7; p = 0.02) and a small effect on executive function (g = 0.37, 95%CI: 0.04-0.69; n = 6; p = 0.03). Aerobic physical activity may improve memory and executive function in sedentary adults without cognitive impairment. Policymakers and providers should promote aerobic physical activity in this population, and further research should investigate the most effective ways to promote aerobic physical activity in mid-life to older adults.

Research Note: Fate and dissemination of Salmonella enterica serovar reading in turkeys at processing using an oral gavage challenge model.

This study aimed to evaluate the fate and dissemination of Salmonella Reading (SR) in turkeys using an oral gavage challenge model. One hundred twenty-eight-week-old commercial turkey hens were moved from commercial production to research facilities. Upon arrival, a combination of enrofloxacin, 10 mg/kg, and florfenicol, 20 mg/kg, were orally administered sequentially before comingled placement on fresh pine shavings. Turkeys were challenged with 108 cfu SR by oral gavage on d 4 and 7 postplacement. Subsets were subjected to simulated commercial processing on d 14 (n = 40), 21 (n = 40) and 28 (n = 32) postplacement (corresponding to 10, 11, and 12 wk of age). Stifle joint, skin, trachea, crop, lung, liver + spleen (LS), and ceca were aseptically sampled and cultured for Salmonella recovery and serotyping. SR could not be recovered from stifle joint 14 d post inoculation (PI). However, at 14 d PI, recovery of SR were: Skin 80%; crop 75%; LS 67.5%; lungs 60%; and ceca 57.5%. (P < 0.01). Interestingly, the lowest recovery of SR was observed from trachea (40%). At 21 d PI, the highest rate of positive samples to SR were observed in ceca (87.5%) and crop (67.5%). By 28 d PI, SR was only recovered from ceca (75%); crop (43.8%); lung (34.4%); and LS (21.9%). The results of this study confirms that SR is an emerging problem for the turkey industry and immediate measurements to reduce foodborne pathogens such as Salmonella should target all parts of the supply chain and consumer education about food safety.

Racial differences in sleep duration intersect with sex, socioeconomic status, and U.S. geographic region: The REGARDS study.

OBJECTIVES: Short and long sleep duration are associated with poor health outcomes and are most prevalent among racial/ethnic minorities. Few studies have investigated the intersection of other sociodemographic characteristics with race/ethnicity on sleep duration prevalence. DESIGN: Longitudinal retrospective analysis of continental U.S. cohort, the REasons for Geographic And Racial Differences in Stroke (REGARDS) PARTICIPANTS: Black (n = 7,547) and white (n = 12,341) adults, 56% women, ≥45 years MEASUREMENTS: At baseline (2003-07), participants reported age, sex, race, education, income, marital status, U.S. region, and employment status. The weighted average of reported sleep duration on weekdays and weekends, assessed at follow-up (2008-10), was categorized as <6, 6.0-6.99, 7.0-7.99 [reference], 8.0-8.99, and ≥9 h. Multinomial logistic regression models examined the independent and multivariable associations of sociodemographic factors with sleep duration. Interactions terms between race with education, income, region, and sex were examined. RESULTS: Average sleep duration was 7.0 h (SD=1.3). Prevalence of short (<6 h) and long (≥9 h) sleep duration was 11.4% (n = 2,260) and 7.0% (n = 1,395), respectively. In the multivariable model, interactions terms race*income, race*sex, and race*region were significant (P < .05). Relative to white adults, black adults, were most likely to have short sleep duration. The magnitude of that likelihood increased across greater levels of household income, but with greatest odds among black adults living outside of the Southeast and Appalachian United States, particularly for men (≥$75k; black men OR = 5.47, 95%CI: 3.94,7.54; black women OR = 4.28, 95%CI: 3.08, 5.96). CONCLUSIONS: Race in the context of socioeconomic, sex, and regional factors should be examined as key modifiers of sleep duration.

Sleep duration and timing in obsessive-compulsive disorder (OCD): evidence for circadian phase delay.

OBJECTIVES: To investigate potential delays in endogenous melatonin in individuals with obsessive-compulsive disorder (OCD). METHODS: First, data are presented for 15 individuals with OCD and matched healthy controls. Next, nine additional participants with OCD who did not have matched controls were added, resulting in a sample of 24 individuals with OCD. All participants were assessed for sleep and circadian rhythm disturbance. Dim light melatonin onset (DLMO) was derived from salivary melatonin and was used in conjunction with sleep diaries, interview measures, and questionnaires. A subset of the OCD group (n = 16) also used actigraphy. RESULTS: In sum, 42% percent (10/24) of the patients with OCD met the criteria for delayed sleep-wake phase disorder (DSWPD) in comparison to 0% in the control sample. DLMO was significantly later in individuals with OCD compared to controls. DLMO and bedtime were not significantly associated with the severity of obsessive-compulsive symptoms or negative affect. CONCLUSIONS: Replication of the findings presented herein, particularly the DLMO results, is warranted. Further, there are now three studies showing that nearly ½ of individuals with OCD meet criteria for a DSWPD. Future studies can explore the mechanisms underlying these connections and the implications of this comorbidity. These findings may increase our understanding of OCD and inform future interventions.

Rationale, design, and development of SleepWell24: A smartphone application to promote adherence to positive airway pressure therapy among patients with obstructive sleep apnea.

BACKGROUND: Positive airway pressure (PAP) therapy is the gold standard treatment for obstructive sleep apnea (OSA), a chronic disorder that affects 6-13% of the adult population. However, adherence to PAP therapy is challenging, and current approaches to improve adherence have limited efficacy and scalability. METHODS/DESIGN: To promote PAP adherence, we developed SleepWell24, a multicomponent, evidence-based smartphone application that delivers objective biofeedback concerning PAP use and sleep/physical activity patterns via cloud-based PAP machine and wearable sensor data, and behavior change strategies and troubleshooting of PAP therapy interface use. This randomized controlled trial will evaluate the feasibility, acceptability, and initial efficacy of SleepWell24 compared to a usual care control condition during the first 60 days of PAP therapy among patients newly diagnosed with OSA. DISCUSSION: SleepWell24 is an innovative, multi-component behavior change intervention, designed as a self-management approach to addressing the psychosocial determinants of adherence to PAP therapy among new users. The results will guide lengthier future trials that assess numerous patient-centered and clinical outcomes.

Applications of mechanistic modelling to clinical and experimental immunology: an emerging technology to accelerate immunotherapeutic discovery and development.

The application of in-silico modelling is beginning to emerge as a key methodology to advance our understanding of mechanisms of disease pathophysiology and related drug action, and in the design of experimental medicine and clinical studies. From this perspective, we will present a non-technical discussion of a small number of recent and historical applications of mathematical, statistical and computational modelling to clinical and experimental immunology. We focus specifically upon mechanistic questions relating to human viral infection, tumour growth and metastasis and T cell activation. These exemplar applications highlight the potential of this approach to impact upon human immunology informed by ever-expanding experimental, clinical and 'omics' data. Despite the capacity of mechanistic modelling to accelerate therapeutic discovery and development and to de-risk clinical trial design, it is not utilized widely across the field. We outline ongoing challenges facing the integration of mechanistic modelling with experimental and clinical immunology, and suggest how these may be overcome. Advances in key technologies, including multi-scale modelling, machine learning and the wealth of 'omics' data sets, coupled with advancements in computational capacity, are providing the basis for mechanistic modelling to impact on immunotherapeutic discovery and development during the next decade.

Catalytic oxidative coupling promoted by bismuth TEMPOxide complexes.

Bismuth(iii) TEMPOxide compounds have been synthesized from the coupling of Bi(ii) species with the TEMPO˙ radical. The steric profile of the supporting bis(amido)disiloxane ligand promotes different fluxional behaviour in solution, and DFT calculations suggest variation in the Bi-O bond character. These compounds are active catalysts for oxidative coupling of TEMPO and silane substrates, believed to proceed via metathesis of Bi-O and Si-H bonds followed by decomposition of bismuth-hydride intermediate species.

Neutral and cationic bismuth compounds supported by bis(amidodimethyl)disiloxane ligands.

Bis(amidodimethyl)disiloxane ligands derived from O{SiMe2N(H)R}2 (abbreviated as (NONR)H2) are a stable support for neutral and cationic bismuth compounds. Attempts to extend the series Bi(NONR)Cl (R = Ar = 2,6-iPr2C6H3; R = tBu) to include compounds where R = Ar' = 2,6-Me2C6H3 were complicated by concomitant formation of the bimetallic compound {Bi(NONAr')}2(µ-NONAr'). Compounds containing [Bi(NONR)]+ cations were obtained from reactions with group 13 chlorides MCl3 (M = Al, Ga). X-ray crystallographic analysis showed intermolecular interactions with the [MnCl(3n+1)] anion.

Hydrophosphination-type reactivity promoted by bismuth phosphanides: scope and limitations.

Phenyl isocyanate inserts into the Bi-P bond of the terminal phosphanide Bi(NONAr)(PCy2) (NONAr = [O(SiMe2NAr)2]2- Ar = 2,6-iPr2C6H3) to afford the κ2N,O-phosphanylcarboxamidate complex. Liberation of the hydrophosphination product from the metal is achieved by reaction with HPPh2. The diphenylphosphanide product, Bi(NONAr)(PPh2), is however unstable and decomposes to generate reduced species, preventing catalytic turnover.

Building confidence in quantitative systems pharmacology models: An engineer's guide to exploring the rationale in model design and development.

This tutorial promotes good practice for exploring the rationale of systems pharmacology models. A safety systems engineering inspired notation approach provides much needed rigor and transparency in development and application of models for therapeutic discovery and design of intervention strategies. Structured arguments over a model's development, underpinning biological knowledge, and analyses of model behaviors are constructed to determine the confidence that a model is fit for the purpose for which it will be applied.

Agent-Based Modeling in Systems Pharmacology.

Modeling and simulation (M&S) techniques provide a platform for knowledge integration and hypothesis testing to gain insights into biological systems that would not be possible a priori. Agent-based modeling (ABM) is an M&S technique that focuses on describing individual components rather than homogenous populations. This tutorial introduces ABM to systems pharmacologists, using relevant case studies to highlight how ABM-specific strengths have yielded success in the area of preclinical mechanistic modeling.

Short-term corneal endothelial response to wear of silicone-hydrogel contact lenses in East Asian eyes.

OBJECTIVE: To evaluate corneal endothelial bleb response to wear of silicone-hydrogel contact lenses in eyes of East Asian subjects. METHODS: A total of 24 subjects of East Asian origin, attended 3 separate sessions for a prospective, single-centre, trial. The following contact lenses were used: ACUVUE ADVANCE with HYDRACLEAR (ADVANCE, -3 dioptres), ACUVUE OASYS with HYDRACLEAR Plus (OASYS, -3 dioptres), Focus NIGHT & DAY (NIGHT & DAY, -3 dioptres) and SofLens 38 (+3 dioptres). A modified Balaam's crossover design was used to randomize presentation of sessions and contact lenses within sessions. Session 1 was a comparison between OASYS and SofLens 38 under closed eye conditions, session 2 was a comparison between ADVANCE and NIGHT & DAY under open eye conditions, and session 3 was a comparison between OASYS and NIGHT & DAY worn under closed eye conditions. Corneal endothelial images were captured with the Topcon SP-3000P noncontact Specular Microscope before lens wear, after 20 mins of wear with lenses on and 5 and 10 mins later after lens removal. Blebs were manually identified on these digital images by a masked observer. The area of blebs and total area under consideration were derived using ImageNet software and used to calculate percentage area of blebs. A boundary of equivalence of 1% was used as a clinically significant bleb area difference, and two-sided 95% confidence intervals were utilized to evaluate differences between lenses within each session. RESULTS: In session 1, SofLens 38 produced a mean percentage area of blebs of 8.0% under closed eye conditions, which was significantly different to that produced by OASYS (1.6%). In session 2, both Advance and Night & Day produced a mean percentage bleb area of 0.4% under open eye conditions. In session 3, OASYS and NIGHT & DAY produced statistically similar mean percentage bleb areas of 1.7% and 2.0%, respectively. CONCLUSIONS: The similarity of bleb responses induced by the silicone-hydrogel lenses under the tested wearing conditions is consistent with the proposition that increases in Dk/t above a certain level will produce minimal change in corneal physiologic conditions compared with that when no lens is worn.