Although critical for informed consent, side effect warnings can contribute directly to poorer patient outcomes because they often induce negative expectations that trigger nocebo side effects. Communication strategies that reduce the development of nocebo side effects whilst maintaining informed consent are therefore of considerable interest. We reviewed theoretical and empirical evidence for the use of framing strategies to achieve this. Framing refers to the way in which information about the likelihood or significance of side effects is presented (e.g., negative frame: 30% will experience headache vs. positive frame: 70% will not experience headache), with the rationale that positively framing such information could diminish nocebo side effects. Relatively few empirical studies (k = 6) have tested whether framing strategies can reduce nocebo side effects. Of these, four used attribute framing and two message framing. All but one of the studies found a significant framing effect on at least one aspect of side effects (e.g., experience, attribution, threat), suggesting that framing is a promising strategy for reducing nocebo effects. However, our review also revealed some important open questions regarding these types of framing effects, including, the best method of communicating side effects (written, oral, pictorial), optimal statistical presentation (e.g., frequencies vs. percentages), whether framing affects perceived absolute risk of side effects, and what psychological mechanisms underlie framing effects. Future research that addresses these open questions will be vital for understanding the circumstances in which framing are most likely to be effective.

Positive framing has been proposed as an intervention to increase COVID-19 vaccination intentions. However, available research has examined fictitious or unfamiliar treatments. This pre-registered study (aspredicted#78369) compared the effect of standard negatively framed EU patient information leaflets (PILs), with new positively framed PILs, on booster intentions (measured pre- and post-intervention) for AstraZeneca, Pfizer, and Moderna COVID-19 vaccines. A representative sample of 1222 UK-based adults was randomised to one of six groups in a factorial design with framing (Positive vs. Negative) and vaccine familiarity (same (as previous), familiar, unfamiliar) as factors. The benefit of positive framing was hypothesised to be strongest for the least familiar vaccine (Moderna). Framing was moderated by familiarity, where only the unfamiliar vaccine showed a benefit of positive relative to negative Framing. Framing and familiarity also interacted with baseline Intention with the effect of framing on the unfamiliar vaccine especially pronounced at low baseline Intent. Conversely, standard negative framing appeared to increase intentions for familiar vaccines at low baseline intent. Findings provide important evidence that positive framing could improve vaccine uptake globally when switches or new developments require individuals to receive less familiar vaccines. Positive framing of familiar vaccines, however, should be treated with caution until better understood.

To evaluate the effect of presenting positively attribute-framed side effect information on COVID-19 booster vaccine intention relative to standard negatively-framed wording and a no-intervention control. A representative sample of Australian adults (N = 1204) were randomised to one of six conditions within a factorial design: Framing (Positive; Negative; Control) × Vaccine (Familiar (Pfizer); Unfamiliar (Moderna)). Negative Framing involved presenting the likelihood of experiencing side effects (e.g., heart inflammation is very rare, 1 in every 80,000 will be affected), whereas Positive Framing involved presenting the same information but as the likelihood of not experiencing side effects (e.g., 79,999 in every 80,000 will not be affected). Booster vaccine intention measured pre- and post-intervention. Participants were more familiar with the Pfizer vaccine (t(1203) = 28.63, p <.001, Cohen's d_z = 0.83). Positive Framing (M = 75.7, SE = 0.9, 95% CI = [73.9, 77.4]) increased vaccine intention relative to Negative Framing (M = 70.7, SE = 0.9, 95% CI = [68.9, 72.4]) overall (F(1, 1192) = 4.68, p =.031, η_p² = 0.004). Framing interacted with Vaccine and Baseline Intention (F(2, 1192) = 6.18, p =.002, η_p² = 0.01). Positive Framing was superior, or at least equal, to Negative Framing and Control at increasing Booster Intention, irrespective of participants' pre-intervention level of intent and vaccine type. Side effect worry and perceived severity mediated the effect of Positive vs. Negative Framing across vaccines. Positive framing of side effect information appears superior for increasing vaccine intent relative to the standard negative wording currently used. See: aspredicted.org/LDX_2ZL.

Topical application of local anesthetics provides safe analgesia following abdominal surgery in people. Conservative doses have been utilized to avoid toxicity. Toxic effects are proportional to amount of drug administered and the plasma concentration of the drug, allowing predictions of safety following pharmacokinetic studies. The maximum plasma level, the pharmacokinetics and the safety of lidocaine hydrochloride when administered by the combined intraperitoneal (8 mg/kg i.p. with epinephrine 1:400 000) and incisional (2 mg/kg with epinephrine 1:200 000) routes were studied in six mixed breed dogs following ovariohysterectomy. Rapid uptake of lidocaine produced a peak concentration of 1.45 ± 0.36 μg/mL (mean ± SD, range 0.80–1.86 μg/mL) by 0.37 ± 0.26 h (range 0.11–0.81) after administration. The absorption half‐life was 0.13 ± 0.1 h. Plasma concentrations decreased rapidly and the elimination half‐life was 1.17 ± 0.11 h. No signs of toxicity were observed in these dogs in the 18 h following drug administration. The dose studied generated levels of lidocaine well below toxic.

Individuals frequently update their beliefs and behaviours based on observation of others' experience. While often adaptive, social learning can contribute to the development of negative health expectations, leading to worsened health outcomes, a phenomenon known as the nocebo effect. This systematic review and meta-analysis examined: whether social learning is sufficient to induce the nocebo effect, how it compares to other forms of induction (classical conditioning and explicit instruction), and factors that influence these effects. The meta-analysis included twenty studies (n = 1388). Social learning showed a medium-large effect size (Hedges' g = .74) relative to no treatment and a to small-medium effect (g = .42) when compared to neutral modelling. The effect of social learning was similar in magnitude to classical conditioning but greater than explicit instruction with a small-medium effect (g = .46). Face-to-face social modelling, longer exposure, higher proportions of female participants and models, and greater observer empathy led to stronger socially-induced nocebo effects. However, further research is essential as only a minority of studies measured important constructs like negative expectancies and state anxiety. Nonetheless, the study highlights social learning as a key pathway for nocebo effects, suggesting it as a target for interventions to reduce the substantial personal and societal burden caused by nocebo effects.