The influence of video-based social modelling on the nocebo effect.

OBJECTIVE: Seeing someone else experience side effects (i.e., social modelling) can increase negative expectations and subsequent nocebo effects. In face-to-face contexts, this effect appears stronger in female participants. Less is known about the influence of gender on negative expectations and nocebo effects generated via video-based social modelling. METHODS: One hundred and seven undergraduate participants recruited from a participant pool at an Australian university took part in a study ostensibly investigating the influence of beta-blocker medications (actually a sham treatment) on physiological and psychological aspects of anxiety. Participants were randomly assigned to either a no-treatment control group, a standard treatment group, or a video modelling group, in which participants viewed video-recorded confederates (one male, one female) report experiencing four side effects (two each) after taking the study treatment. Symptoms were assessed 15-min following pill ingestion, and at follow-up 24 h later. RESULTS: Video modelling of side effects, compared to standard treatment, interacted with gender and was associated with increased reporting of modelled symptoms in female compared to male participants, p = .01, ηp2=0.06. Video modelling also increased negative expectations in female compared to male participants, p = .03, ηp2=0.07, and expectations mediated the influence of modelling on modelled symptoms in female participants. CONCLUSIONS: Social modelling of side effects via video increased negative expectations, and nocebo symptoms, to a greater extent in female participants. These findings suggest that males and females are differentially impacted by video-based side effect modelling. Results have implications for social modelling of side effects via social media and patient-support websites.

Association of Single-blind Placebo Run-in Periods With the Placebo Response in Randomized Clinical Trials of Antidepressants: A Systematic Review and Meta-analysis.

Importance: Single-blind placebo run-in (PRI) periods are common in randomized clinical trials (RCTs) of treatment for depression. They aim to increase sensitivity to detect drug effects; however, the association of PRI periods with study outcomes remains unclear. This is concerning given the costs of PRI periods to patients and investigators. Objective: To examine the association of the use of PRI periods with the placebo response, drug response, and drug-placebo difference among RCTs of antidepressants. Data Sources: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and PsycINFO, as well as repositories of unpublished studies, were systematically searched up to July 2021. Study Selection: Included studies were double-blind, placebo-controlled RCTs of antidepressant medication among adults with depressive disorders. Data Extraction and Synthesis: Data were extracted into a coding sheet, including the characteristics of studies, the characteristics of PRI periods, and the outcomes of studies. Main Outcomes and Measures: Study outcomes were the primary depression symptom measure reported by the RCT. These outcomes were used to calculate effect sizes (Hedges g) of the within-group drug response and placebo response as well as the drug-placebo difference. Random-effects meta-analysis was used to calculate effect sizes, and subgroup analyses were used to compare outcomes depending on use of PRI periods. Results: A total of 347 trials (representing 89 183 participants) were included; 174 studies (50%) reported using a single-blind PRI period. Response outcome data were available for 189 studies. Studies using PRI periods reported a smaller placebo response (g = 1.05 [95% CI, 0.98-1.11]; I2 = 82%) than studies that did not use a PRI period (g = 1.15 [95% CI, 1.09-1.21]; I2 = 81%; P = .02). Subgroup analysis showed a larger drug response size among studies that did not use a PRI period (g = 1.55 [95% CI, 1.49-1.61]; I2 = 85%) than those that did use a PRI period (g = 1.42 [95% CI, 1.36-1.48]; I2 = 81%; P = .001). The drug-placebo difference did not differ by use of PRI periods (g = 0.33 [95% CI, 0.29-0.38]; I2 = 47% for use of a PRI period vs g = 0.34 [95% CI, 0.30-0.38]; I2 = 54% for no use of PRI periods; P = .92). The likelihood of response to drug vs placebo also did not differ between studies that used a PRI period (odds ratio, 1.89 [95% CI, 1.76-2.03]) and those that did not use a PRI period (odds ratio, 1.77 [95% CI, 1.65-1.89]; P = .18). Conclusions and Relevance: This study suggests that RCTs using PRI periods yield smaller within-group changes across both placebo and drug groups compared with RCTs without PRI periods. The reduction in effect size across groups was equivalent in magnitude. Consequently, PRI studies do not observe larger drug-placebo differences, suggesting that they do not increase trial sensitivity. As such, given the resources and probable deception required and risk to external validity, the practice of using PRI periods in RCTs of antidepressants should be ended.

Protocol for the avatar acceptability study: a multiperspective cross-sectional study evaluating the acceptability of using patient-derived xenografts to guide personalised cancer care in Australia and New Zealand.

INTRODUCTION: Patient-derived xenografts (PDXs) have the potential to transform personalised cancer care, however, little is known about the acceptability of using PDXs to guide treatment decision-making. Given that patient and community preferences can influence satisfaction with care as well as the success of new technologies, we will evaluate the acceptability of PDXs in individuals affected by cancer and community comparisons. METHODS AND ANALYSIS: This comparative cross-sectional study will recruit 323 individuals affected by cancer (cancer survivors (of childhood or adult cancer) and parents of childhood cancer survivors) and 323 community comparisons (adults and parents). We will collect data via structured interviews and questionnaires. To determine the acceptability of PDXs, we will assess five domains: willingness to use PDXs when/if diagnosed with cancer, perceived advantages and disadvantages of PDXs, maximum acceptable out-of-pocket costs per patient, maximum acceptable turnaround time to receive results and maximum acceptable number of mice sacrificed per patient. The primary endpoint will be participants' decisional balance ratio (calculated as participants' advantages ratings divided by perceived disadvantages ratings). ETHICS AND DISSEMINATION: The study protocol has been approved by the South Eastern Sydney Local Health District Human Research Ethics Committee (HREC:12/173) and UNSW Sydney (HC15773). The results will be disseminated in peer-reviewed journals and at scientific conferences. A lay summary will be published on the Behavioural Sciences Unit website.

Using Learning Strategies to Inhibit the Nocebo Effect.

Learning is a key mechanism underpinning the development of the nocebo effect. The learning literature has cataloged and explored numerous ways in which the environment can be manipulated to prevent, reduce, or eradicate learning. Knowledge of these processes could be used to both inhibit the development of nocebo effects and reduce already established nocebo learning. This review describes the available evidence on how such learning strategies have, or could be, applied to reduce the nocebo effect in both healthy participants and patients to date. These learning strategies include overshadowing, latent inhibition, extinction, and contingency degradation. These strategies represent important new avenues for investigation and should be used by researchers to design and test interventions to reduce nocebo effects.

Psychological outcomes and surgical decisions after genetic testing in women newly diagnosed with breast cancer with and without a family history.

In patients with early breast cancer, personal and tumour characteristics other than family history are increasingly used to prompt genetic testing to guide women's cancer management (treatment-focused genetic testing, 'TFGT'). Women without a known strong family history of breast and/or ovarian may be more vulnerable to psychological sequelae arising from TFGT. We compared the impact of TFGT in women with (FH+) and without (FH-) a strong family history on psychological adjustment and surgical decisions. Women aged <50 years with high-risk features were offered TFGT before definitive breast cancer surgery and completed self-report questionnaires at four time points over 12 months. All 128 women opted for TFGT. TFGT identified 18 carriers of a disease-causing variant (50.0% FH+) and 110 non-carriers (59.1% FH+). There were no differences based on family history in bilateral mastectomy (BM) uptake, p = .190, or uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO), p = .093. FH- women had lower decreases in anxiety a year after diagnosis, p = .011, and regret regarding their decision whether to undergo BM, p = .022, or RRBSO, p = .016 than FH + women. FH- carriers reported significantly higher regret regarding their TFGT choice (p = .024) and test-related distress (p = .012) than FH + carriers, but this regret/distress could not be attributed to a concern regarding a possible worse prognosis. These findings indicate that FH- women may require additional counselling to facilitate informed decisions. Carriers without a family history may require additional follow-up counselling to facilitate psychological adjustment to their positive variant results, extra support in making surgical decisions, and counselling about how best to communicate results to family members.

Parent-targeted home-based interventions for increasing fruit and vegetable intake in children: a systematic review and meta-analysis.

Context: Parent interventions delivered in the home represent a valuable approach to improving children's diets. Objective: This review aims to examine the effectiveness of parent-targeted in-home interventions in increasing fruit and vegetable intake in children. Data Sources: Five electronic databases were searched: MEDLINE, Embase, PubMed, CINAHL, and PsycINFO. Study Selection: Randomized and nonrandomized trials conducted in children aged 2 to 12 years and published in English from 2000 to 2016 were eligible. Data Extraction: Eighteen publications were reviewed, and 12 randomized trials were analyzed. Studies were pooled on the basis of outcome measure and type of intervention, resulting in 3 separate meta-analyses. Results: Nutrition education interventions resulted in a small but significant increase in fruit intake (Hedges' g = 0.112; P = 0.028). Taste exposure interventions led to a significant increase in vegetable intake, with a moderate effect (Hedges' g = 0.438; P < 0.001). Interventions involving daily or weekly sessions reported positive outcomes more frequently than those using monthly sessions. Conclusions: Future interventions should incorporate regular taste exposure to maximize increases in vegetable intake in children. This is particularly important because fewer children meet national recommendations for vegetable intake than for fruit intake.

Autonomic Arousal as a Mechanism of the Persistence of Nocebo Hyperalgesia.

Placebo and nocebo mechanisms can lead to clinically significant modulation of pain. Although learning is considered to be the broad mechanism underlying placebo analgesia as well as nocebo hyperalgesia, critical differences have emerged in their specific mechanisms. One of the most interesting of these is that whereas placebo analgesia seems to be relatively short-lived, nocebo hyperalgesia appears more resistant to extinction, often persisting indefinitely. The current study examined why nocebo hyperalgesia persists longer than placebo analgesia. Sixty healthy volunteers were randomized to receive placebo conditioning, nocebo conditioning, or no conditioning using an experimental pain model with surreptitious decreases (placebo group) and increases (nocebo group) in pain stimulation paired with sham treatment during training. Pain was then assessed in a test phase with and without the sham treatment at equal pain stimulation. The conditioning procedure successfully induced placebo analgesia as well as nocebo hyperalgesia in the relevant groups, with nocebo hyperalgesia outlasting placebo analgesia, confirming nocebo hyperalgesia's resistance to extinction. Most interestingly, nocebo treatment led to heightened anticipatory anxiety ratings and autonomic arousal. Further, autonomic arousal completely mediated the effect of nocebo versus placebo training on extinction, suggesting that heightened autonomic arousal may be an important mechanism in the persistence of nocebo hyperalgesia. PERSPECTIVE: Heightened anticipatory anxiety in the form of elevated autonomic arousal may explain why nocebo hyperalgesia persists relative to placebo analgesia. As such, interventions that reduce anticipatory anxiety could reduce the burden of persistent nocebo hyperalgesia.

Family history-taking practices and genetic confidence in primary and tertiary care providers for childhood cancer survivors.

BACKGROUND: There is growing impetus for increased genetic screening in childhood cancer survivors. Family history-taking is a critical first step in determining survivors' suitability. However, the family history-taking practices of providers of pediatric oncology survivorship care and the confidence of these providers to discuss cancer risks to relatives are unknown. PROCEDURE: Fifty-four providers completed semistructured interviews in total, which included eight tertiary providers representing nine hospitals across two countries (63% male, 63% oncologists, 37% nurses) and 46 primary care providers (PCPs) nominated by a survivor (59% male, 35% regional practice). We used content analysis and descriptive statistics/regression to analyze the data. RESULTS: Few tertiary (38%) or primary (35%) providers regularly collected survivors' family histories, often relying on survivors/parents to initiate discussions. Providers mostly took two-generation pedigrees (63% tertiary and 81% primary). Primary providers focused on adult cancers. Lack of time, alternative priorities, and perceived lack of relevance were common barriers. Half of all tertiary providers felt moderately comfortable discussing genetic cancer risk to children of survivors (88% felt similarly discussing risks to other relatives). Most primary providers lacked confidence: 41% felt confident regarding risks to survivors' children and 48% regarding risks to other relatives. CONCLUSIONS: While family history-taking will not identify all survivors suitable for genetics assessment, recommendations for regular history-taking are not being implemented in tertiary or primary care. Additional PCP-targeted genetic education is warranted given that they are well placed to review family histories of pediatric cancer survivors.

Distance-delivered physical activity interventions for childhood cancer survivors: A systematic review and meta-analysis.

This review aimed to determine the feasibility of distance-delivered physical activity (PA) interventions in childhood cancer survivors (CCS), and assess the effect on PA levels, and physical, physiological and psychological outcomes. We searched electronic databases until May 2016, including studies following intensive treatment. Meta-analyses were conducted on randomized controlled trials. We calculated the effect of interventions on PA levels and physical, physiological and psychological health outcomes. Thirteen studies (n=270 participants) were included in the systematic review and four (n=102 participants) in the meta-analysis. Most studies used telephone to deliver interventions with contact (1/day-1/month), duration (2 weeks-1year) and timing (maintenance therapy->20years following intensive treatment) varying between interventions. Interventions yielded a mean recruitment rate=64%, retention rate=85% and adherence rate=88%. Interventions did not increase PA levels (p=0.092), but had a positive effect on physical function (p=0.008) and psychological outcomes (p=0.006). Distance-delivered PA interventions are feasible in CCS. Despite not increasing PA levels, participation may improve physical and psychological health; however, larger randomized controlled trials are warranted.

Family Communication, Risk Perception and Cancer Knowledge of Young Adults from BRCA1/2 Families: a Systematic Review.

Understanding challenges in familial communication of cancer risk has informed genetic service delivery. Parent-child interactions have received considerable attention, but few studies focus on young adulthood experiences within BRCA1/2 families. Young adults are approaching, or at a life stage where awareness of hereditary cancer risk is vital for informed choice of risk management options. This review assesses family communication, risk perception and cancer knowledge held by 18-40 year old individuals who have a parent with a BRCA1/2 gene mutation or carry the gene mutation themselves. Thirteen papers met the inclusion criteria. One utilized a 'mixed methods' methodology and the remaining used a qualitative approach. Findings were synthesized into themes and reported narratively. In general, parents are communicating openly about genetic risk with young adult offspring, but there is evidence that some young adults are withholding information from their parents about their own test results. Risk perception is influenced by a family history of cancer, childbearing plans and health providers' advice. Misconceptions about genetic risk appear to be common and gaps in hereditary cancer knowledge are evident. It is unclear whether incorrect knowledge was passed from parents to offspring. Health providers need to provide developmentally appropriate services for emerging adults (18-25 years old), with particular support in navigating through risk management options.

Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial.

PURPOSE: Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. METHODS: In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. RESULTS: A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). CONCLUSION: A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456.

Sources of Placebo-Induced Relief From Nausea: The Role of Instruction and Conditioning.

OBJECTIVES: It is well documented that expectancies alter the nauseous response. However, the lack of integration in research examining sources of expectancy has limited our understanding of how expectancies are formed and, consequently, our ability to intervene. The present study explored the role of both instructions and conditioning in placebo-induced relief from nausea. METHODS: The study used a 2 × 2 between-subjects design with instruction and conditioning as factors with 56 healthy volunteers. The instruction manipulation involved randomizing participants to receive information that a sham treatment (a peppermint essence vapor) would reduce nausea or no such instructions. The conditioning manipulation involved further randomizing participants to have the first administration of this sham treatment paired with a surreptitious reduction in galvanic vestibular stimulation (GVS) intensity or no prior pairing. Nausea was induced through GVS. On test, all groups received the same level of GVS with the sham treatment present. RESULTS: On test, participants who received instruction had significantly lower nauseous response scores than those who did not (F(1,46) = 6.71, p = .013), and those who received conditioning also reported less nausea than those who did not (F(1,46) = 5.20, p = .027), with the interaction between the two not reaching statistical significance (F(1,46) = 2.33, p = .13). CONCLUSIONS: These findings indicate that placebo responding in nausea can be induced both through positive instructions and as little as one pairing of a treatment with a reduction in nausea, as well as their combination. This suggests that using placebo effects to complement antiemetic therapy may offer an important method of further reducing nausea in the clinic.

Acceptability of, and Information Needs Regarding, Next-Generation Sequencing in People Tested for Hereditary Cancer: A Qualitative Study.

Next generation sequencing (NGS) for patients at risk of hereditary cancer syndromes can also identify non-cancer related mutations, as well as variants of unknown significance. This study aimed to determine what benefits and shortcomings patients perceive in relation to NGS, as well as their interest and information preferences in regards to such testing. Eligible patients had previously received inconclusive results from clinical mutation testing for cancer susceptibility. Semi-structured telephone interviews were subjected to qualitative analysis guided by the approach developed by Miles and Huberman. The majority of the 19 participants reported they would be interested in panel/genomic testing. Advantages identified included that it would enable better preparation and allow implementation of individualized preventative strategies, with few disadvantages mentioned. Almost all participants said they would want all results, not just those related to their previous diagnosis. Participants felt that a face-to-face discussion supplemented by an information booklet would be the best way to convey information and achieve informed consent. All participants wanted their information stored and reviewed in accordance with new developments. Although the findings indicate strong interest among these individuals, it seems that the consent process, and the interpretation and communication of results will be areas that will require revision to meet the needs of patients.

Nocebo Hyperalgesia, Partial Reinforcement, and Extinction.

UNLABELLED: Many studies have found evidence of conditioning-induced nocebo hyperalgesia. However, these studies have exclusively involved continuous reinforcement (CRF) schedules. Thus, it is currently unknown whether nocebo hyperalgesia can result after partial reinforcement (PRF). We tested this using electrodermal pain stimulation in healthy volunteers. Undergraduates (N = 135) received nocebo treatment under the guise of a hyperalgesic. Participants were randomly allocated to CRF, PRF, or control (no conditioning). Conditioning involved surreptitiously increasing pain stimulation on nocebo trials relative to control trials. During training, the CRF group always had the nocebo paired with the surreptitious pain increase, whereas the PRF group experienced the increase on only 62.5% of nocebo trials. In the test phase, pain stimulation was equivalent across nocebo and control trials. PRF was sufficient to induce nocebo hyperalgesia; however, this was weaker than CRF. Nocebo hyperalgesia failed to extinguish irrespective of the training schedule. Additional assessment of expectancies indicated strong concordance between expectancy and nocebo hyperalgesia. Overall, these findings suggest that once established, nocebo hyperalgesia may be difficult to disrupt. PRF may be a novel method of reducing the intensity of nocebo hyperalgesia in the clinic, which may be particularly important given its persistence. PERSPECTIVE: This study provides novel evidence that partial reinforcement results in weaker nocebo hyperalgesia than continuous reinforcement and that nocebo hyperalgesia fails to extinguish, irrespective of the training schedule. As a result, partial reinforcement may serve as a method for reducing the intensity of nocebo hyperalgesia in the clinic.

Placebo interventions for nausea: a systematic review.

BACKGROUND: Expectancy often predicts nausea, but the extent to which placebo interventions can alter nausea is less clear. PURPOSE: We conducted a systematic review to determine 1) if placebo interventions can affect nausea and 2) which features of these interventions are effective. METHODS: Articles were identified via PsychInfo, Medline, and PubMed databases. We targeted instructional and conditioning interventions aimed at altering nausea via the placebo effect. RESULTS: Fourteen studies were identified, nine instructional and five conditioning. Many found evidence suggesting that placebo interventions could alter nausea, but a few found no evidence or 'reverse' effects. Effective interventions tended to be those that were aimed at participants with high initial expectancies, with evidence that combined or conditioning manipulations were more effective than instructions. CONCLUSIONS: These findings suggest that placebo interventions can alter nausea and that these may serve as a useful way of reducing the burden of nausea in practice.

Preferences regarding targeted education and risk assessment in people with a family history of major depressive disorder.

Genetic testing for susceptibility to major depressive disorder (MDD) is not available for clinical use at present. Given this, family history remains the best predictor for development of MDD, and family-history-based risk assessment and information about familial aspects of MDD may be useful to clients at increased risk for MDD attending for genetic counseling. This study uses a mixed-methods design to assess the information needs and preferences of people at increased familial risk for MDD. Telephone interviews were conducted with 23 individuals, who had at least one first-degree relative with MDD and were recruited through advertisements placed on depression education websites. The most preferred way to access depression information was via the internet (87 % of participants), although this preference may have been due to the internet-based recruitment method. The second most preferred dissemination strategy (56 %) was face-to-face delivery through a health professional, including genetic counselors. Individuals reported a need for information about etiology and development of MDD, reproductive decision-making, early detection of symptoms and risk-reducing strategies. Nearly all participants expressed an interest in risk assessment. The present study found evidence of a high level of interest for information targeted to people at increased familial risk for MDD. Genetic counselors are likely to be called upon increasingly to provide supportive counseling to assist clients at increased familial risk in interpreting and contextualizing such information once it becomes available.