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ABSTRACTPertussis vaccination of parents and household contacts (‘cocooning’) to protect newborn infants is an established strategy in many countries, although uptake may be low. Many aspects may influence such decision-making. We conducted a cross-sectional survey (NCT01890447) of households and other close contacts of newborns aged ≤6 months (or of expectant mothers in their last trimester) in Spain and Italy, using an adaptive discrete-choice experiment questionnaire. Aims were to assess the relative importance of attributes influencing vaccine adoption, and to estimate variation in vaccine adoption rates and the impact of cost on vaccination rates. Six hundred and fifteen participants (Spain, n = 313; Italy, n = 302) completed the survey. Of 144 available questionnaire scenarios, the most frequently selected (14% of respondents in both countries) were infant protection by household vaccination at vaccination center, recommendation by family physician and health authorities, with information available on leaflets and websites. The attribute with highest median relative importance was ‘reduction in source of infection’ in Spain (23.1%) and ‘vaccination location’ in Italy (18.8%). Differences between other attributes were low in both countries, with media attributes showing low importance. Over 80% of respondents indicated a definite or probable response to vaccine adoption (at no-cost) with estimated probability of adoption of 89–98%; applying vaccine costs (25€ per person) would reduce the probability of uptake by 7–20% in definite/probable respondents. Awareness of these determinants is helpful in informing Health Authorities and healthcare practitioners implementing a cocooning strategy for those populations where maternal immunization is not a preferred option.

Supplemental digital content is available in the text.To assess the primary metabolite of norepinephrine, 3,4-dihydroxyphenylglycol (DHPG), as a sensitive biomarker for norepinephrine transporter (NET) function and the relationship of DHPG measured peripherally and centrally, NET was antagonized with 80 mg/d atomoxetine for 18 days. Twelve healthy subjects were treated with atomoxetine in an open-label, multiple-dose exploratory study. Plasma atomoxetine reached steady state by day 6, and the pharmacokinetic results demonstrated availability of atomoxetine to the central nervous system. The cerebrospinal fluid (CSF)/plasma ratios of atomoxetine based on area under concentration-time curve from 0 to 12 hours postdose (AUC0–12), maximum concentration (Cmax), and predose were 0.3%, 0.2%, and 11%, respectively. Plasma from atomoxetine-treated subjects (ex vivo) significantly inhibited radioligand binding to human NET (P< 0.001) only 1 hour after dosing. Plasma DHPG and DHPG/norepinephrine (ratio) during repeated posture tests were reduced significantly (P< 0.001) on day 5 and stayed significantly reduced up to 1 day after treatment. In CSF, both DHPG and the ratio were significantly reduced (P< 0.001) on day 18. Urine results showed significant decreases for both DHPG and the ratio (P= 0.010 to P< 0.001). Brain-derived neurotrophic factor in CSF was lesser than the limits of detection. The findings suggest that NET blockade can be assessed with DHPG concentration or with the ratio in plasma, CSF, and urine. The data suggest that DHPG is a useful biomarker to proactively assess the pharmacological activity of compounds intended to inhibit NET activity within the brain. The study shows that CSF is a medium for early identification and quantification of biomarkers useful in assessing novel neuroscience targets.