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Funding | The Molecular Screening and Therapeutics (MoST) Program is funded by the Commonwealth, as well as the NSW governments via the Office of Health and Medical Research, NSW. Open Access funding enabled and organized by CAUL and its Member Institutions. | PMC10403555 | ||
Data availability | The molecular data that forms the basis for MTB recommendations are available upon reasonable request. The authors declare that the data supporting the findings of this study are available within the paper and its supplementary appendix. | PMC10403555 | ||
Competing interests | ONCOLOGY | DT as CEO of Omico, a non-profit organisation has received grants, consultancies or research support from Roche, Astra Zeneca, Pfizer, Eisai, Illumina, Beigene, Elevation Oncology, RedX Pharmaceuticals, Sun-Pharma, Bayer, Abbvie, George Clinical, Janssen, Merck, Kinnate, Microba, BioTessellate, Australian Unity, Foundation Medicine, Guardant, Intervenn, Amgen, Seattle Genetics and Eli Lilly. DT also serves on the advisory boards or committees for Canteen, UNSW SPHERE and NSW government in respect to genomics and translational medicine. | PMC10403555 | |
Ethics approval and consent to participate | Not applicable. | PMC10403555 | ||
Consent for publication | Not applicable. | PMC10403555 | ||
References | PMC10403555 | |||
Introduction | depression | Perinatal depression is common among women living with HIV, but depression care is limited in low-resource settings. We examined (1) characteristics of women receiving Problem Solving Therapy (PST) versus antidepressant therapy (ADT), (2) treatment response by modality, and (3) correlates of treatment response. | PMC10564822 | |
Methods | depression | REGRESSION | This analysis used data from 191 Ugandan women in the intervention arm of a cluster randomized controlled trial of task-shifted, stepped-care depression treatment for pregnant women living with HIV (PWLWH). Treatment response was defined as scoring < 5 on the nine-item Patient Health Questionnaire (PHQ-9). Bivariate analysis and multivariable logistic regression were used to examine characteristics of women by treatment group and correlates of treatment response. | PMC10564822 |
Results | depression, congenital defects | MINOR | Of 134 participants with depression, 129 (96%) were treated: 84 (65%) received PST and 45 (35%) received ADT. Severe depression at treatment initiation was more common in those receiving ADT (28.9% versus 4.8%, Fischer’s Exact Test < 0.001). Treatment response was higher for PST (70/84; 83.3%) than ADT (30/45; 66.7%; p = .03). ADT side effects were rare and minor; no infants had serious congenital defects. Of 22 participants (19%) who did not respond to treatment, only five received intensified management. Social support and interpersonal violence were associated with treatment response (adjusted odds ratio, [aOR] = 3.06, 95% CI = 1.08–8.66 and aOR = 0.64, 95% CI = 0.44–0.93). | PMC10564822 |
Discussion | depression | Both depression treatment modalities yielded high response rates in Ugandan PWLWH; ADT was well-tolerated. Our results highlight a need to build capacity to implement the stepped-care protocol for non-responders and screen for social support and interpersonal violence. | PMC10564822 | |
Supplementary Information | The online version contains supplementary material available at 10.1007/s10995-023-03741-1. | PMC10564822 | ||
Supplementary Information | The online version contains supplementary material available at 10.1007/s10995-023-03741-1. | PMC10564822 | ||
Keywords | Open access funding provided by SCELC, Statewide California Electronic Library Consortium | PMC10564822 | ||
Introduction | depression, Depression | Perinatal depression is common among pregnant women living with HIV (PWLWH), with approximately one in three meeting criteria for clinical depression in sub-Saharan Africa (SSA) (Sowa, et al., While evidence-based treatments for perinatal depression exist (Yonkers, et al., To contribute to this body of evidence, we are conducting a cluster randomized controlled trial (Maternal Depression Treatment in HIV, M-DEPTH). Drawing on evidence-based collaborative care models for depression in low-resource settings (Patel, et al., | PMC10564822 | |
Methods | PMC10564822 | |||
Study Design | Details of this prospective, multi-site cluster randomized controlled trial, which follows CONSORT guidelines, can be found elsewhere (Wagner, et al., | PMC10564822 | ||
Study Participants | opportunistic infections | OPPORTUNISTIC INFECTIONS | To be eligible for this study, adult PWLWH had to score > 0 on the PHQ-2, which is administered by peer mothers at all ANC visits. Potential participants were further evaluated by a nurse who applied the following inclusion criteria: (1) gestation period of 32 weeks or less, (2) medically stable without opportunistic infections and on antiretroviral therapy (ART) for at least 4 weeks, (3) age 18 years or older, and (4) scored > 4 on the nurse-administered 9-item Patient Health Questionnaire (PHQ-9) (Kroenke, et al., | PMC10564822 |
M-DEPTH Depression Care Model | The M-DEPTH Depression Care model consisted of (1) | PMC10564822 | ||
Problem Solving Therapy (PST) | PST is a cognitive-behavioral intervention that teaches patients to use adaptive problem solving and systematically apply four skills: defining the problem, generating solutions, selecting solutions, and implementing/evaluating those solutions (Bell et al. | PMC10564822 | ||
Antidepressant Therapy (ADT) | depression | ADT was administered and monitored by nurses, beginning in the second trimester to balance benefits with risks to the developing fetus. Fluoxetine, a selective serotonin reuptake inhibitor (SSRI), at a starting daily dose of 20 mg was the first-line medication, and imipramine, a tricyclic antidepressant, at a starting daily dose of 50 mg (increasing to 75 mg after the first week) was the second-line option. At monthly follow-up visits, measures of treatment response and assessment of side effects guided changes to dosage or medication. Participants receiving ADT were instructed to monitor their infant for signs of poor neonatal adaptation after birth. When the participant’s PHQ-9 was < 5 for six months, and she was at least six months post-pregnancy completion, medication discontinuation was considered.If a patient’s PHQ-9 scores indicated she was not responding to treatment or was experiencing a relapse of symptoms after initial response, depression management was to be “stepped-up” in intensity. This stepped-care approach could include adding the other modality (e.g., ADT if receiving PST or vice versa), switching from PST to ADT, or increasing ADT dosage. | PMC10564822 | |
Measures | depression, Depression, respiratory distress, trauma | CONGENITAL CONDITIONS, SECONDARY | Assessments included surveys, laboratory viral load testing, pharmacy data, and data abstracted from medical charts and a Depression Care Registry maintained by peer mothers and nurses. Survey measures were interviewer-administered; those that had not been translated into Luganda, the local language, during our prior research were translated using standard translation and back-translation methods.Response to depression treatment is the focus of this analysis. At baseline and two months post-pregnancy completion, the PHQ-9, which has been used successfully in rural Uganda (Nakku, et al., Survey measures included sociodemographic characteristics (age and any secondary education); pregnancy-related characteristics (gestation length, pregnancy outcome, whether pregnancy was planned); health functioning and quality of life; depression treatment-related factors (PHQ-9 at treatment initiation, weeks on treatment); relationship factors (e.g., relationship status, partner knowledge of patient’s HIV status, partner support and involvement in the pregnancy; and experience with interpersonal violence [IPV]); experience of trauma (childhood or recent); PMTCT knowledge and attitudes; and problem solving orientation (positive, negative, or avoidant). Surveys also asked about any ADT side effects, degree to which they interfered with daily life, and infant signs of poor neonatal adaptation (i.e., jitteriness, respiratory distress). Mothers were asked if they sought medical care for these signs.Data related to HIV diagnosis and care (e.g., time since diagnosis, whether ART was started during current pregnancy) and whether the infant had any serious congenital conditions were abstracted from the patient’s clinical chart. An HIV viral load assay was collected at baseline and two months post-pregnancy completion, and percent of prescribed ART pills taken was calculated using pharmacy refill data.The Online Supplement provides additional detail on these measures. | PMC10564822 |
Statistical Analysis | depression | REGRESSION, SECONDARY | We used descriptive statistics to examine depression treatment response by modality (PST or ADT) and the presence of side effects. We conducted bivariate analyses to examine differences in patient characteristics between those treated with PST versus ADT, and those whose depression did or did not respond to treatment. We used chi-squared tests for categorical variables and two-tailed independent t-tests for continuous variables, with an We used multivariable logistic regression models, estimated using SAS Proc Surveylogistic, to further examine predictors of treatment response using variables found to be significant correlated with response in bivariate analyses. These models were adjusted for baseline demographics (age, any secondary education, relationship status), weeks on depression treatment, and study site. Analyses were conducted using SAS version 9.2 (SAS Institute, Cary, NC). | PMC10564822 |
Results | PMC10564822 | |||
Sample Characteristics | depression, SD, depressive symptoms | SECONDARY | The intervention arm consisted of 191 PWLWH (out of 391 PWLWH enrolled in the trial overall). Baseline characteristics of those in the intervention arm included mean age of 27.3 (SD = 5.7) years, 41% had any secondary education, 81% were in a committed relationship, mean gestation was 21.3 weeks (SD = 6.4), 22% were newly diagnosed with HIV, and 57% had an undetectable HIV viral load.Of the 191 PWLWH, 122 (63.8%) met criteria for clinical depression (PHQ-9 > 9) at baseline and 117 (95.9%) of those received depression treatment. Of the five participants who were not started on treatment at baseline, two declined treatment, two were lost to follow-up or transferred their care elsewhere, and one had a rapid decrease in her PHQ-9 score before initiating treatment. An additional 12 participants with mild depressive symptoms at baseline, (PHQ-9 between 5 and 9), reported increased depression (PHQ-9 > 9) in the weeks following study enrollment (range: 2–13 weeks after enrollment), and were initiated on treatment. Therefore, a total of 129 (96.2%) of the 134 participants who met criteria for clinical depression either at baseline or after study enrollment received depression treatment, 84 (65.1%) of whom began PST and 45 (34.8%) of whom began ADT.Depressive symptoms at treatment initiation were more severe among those treated with ADT compared to PST, based on mean (SD) PHQ-9 ([16.4 (4.1) vs. 13.3 (3.2); p < .001] and the proportion of participants with severe depression (PHQ-9 > 19; 28.9% vs. 4.8%; Fischer’s Exact Test < 0.001). Participants initiated on ADT were younger [mean (SD) age = 25.2 (5.4) vs. 28.4 (5.3); p < .001] and had higher HIV viral loads at baseline [mean (SD) log | PMC10564822 |
Treatment Effects on PHQ-9 Scores | PMC10564822 | |||
Overall | depression | REMISSION | Of the 129 participants who received depression treatment with PST or ADT, 100 (77.5%) responded to treatment (PHQ-9 < 5) at some point during the study and remained in remission at the conclusion of treatment (or at study completion for those who remained on ADT).PHQ-9 scores at the start of treatment were significantly higher among participants who did not respond to treatment than among those who did [15.9 (SD = 4.0) vs. 14.0 (SD = 3.7), p = .018], as was the proportion of participants with severe depression (27.6% vs. 9.0%, p = .009). The response rate was significantly higher among those treated with PST (70/84; 83.3%) compared to those treated with ADT (30/45; 66.7%) (p = .031). | PMC10564822 |
By Treatment Modality: Problem Solving Therapy | depression | REMISSION | Among the 84 participants who were treated with PST, the mean number of sessions attended was 5.9 (SD = 2.1; median = 6); 78 (92.9%) completed the three core sessions, and 74 of those 78 (94.9%) completed additional sessions. A total of 74 women (88.1%) responded to PST at some point in the study. Treatment response was achieved after a mean of 13.1 weeks (SD = 7.6), and the mean PHQ-9 at the conclusion of treatment was 1.9 (SD = 2.5). Among the 74 who responded, 17 (23.0%) experienced a relapse of depression, of whom 13 had their depression return to a state of remission [PHQ-9 < 5; mean (SD) PHQ-9 = 3.4 (2.8)] by the end of treatment. Therefore, 70 (83.3%) participants responded to PST overall.Of the 10 (11.9%) whose depression never responded to PST, 4 prematurely discontinued treatment. ADT was added to PST for only one of the 10 participants who did not respond, but not for any of the 17 who experienced a relapse. | PMC10564822 |
By Treatment Modality: Antidepressant Therapy | depression | REMISSION | Among the 45 participants who received ADT, 43 (95.6%) were prescribed fluoxetine and 2 (4.4%) received imipramine; only one woman had a dosage increase of her medication. At this point in the ongoing study, mean number of months of ADT is 9.3 (SD = 4.8; range: 2 weeks to 25 months). Thirty-three women (73.3%) responded to ADT after a mean of 19.2 weeks (SD = 14.0), and the mean PHQ-9 at the conclusion of either treatment or study participation was 1.9 (SD = 2.0).Among the 33 participants who responded to ADT,13 (39.4%) experienced worsening of their depression after initial response, including three who began receiving PST in addition to ADT. Among these 13, 10 (78.6%) (including the three who received augmentative PST) had their depression return to a state of remission at the end of treatment or the study. Therefore, 30 (66.7%) participants responded to ADT overall.Of the 12 (26.7%) whose depression never responded to ADT, 4 prematurely discontinued treatment, 3 added PST (two of which then responded to treatment), and 1 was switched to PST from ADT. | PMC10564822 |
Side Effects of Antidepressant Therapy | SAID | Of the 45 participants who received ADT, 40 (88.9%) provided data about side effects at the postpartum assessment. Nine participants (22.5%) reported side effects, of whom five said they were “somewhat” bothersome and 1 said they interfered “more than a little” with daily life. When asked about physical signs in their infant that could have been related to | PMC10564822 | |
Discussion | depression | The treatment response rate among Ugandan PWLWH receiving depression care using an evidence-based collaborative care model was high overall, consistent with other studies, (Patel, et al., Nearly all (96%) participants who were identified as having depression received treatment, and over three-quarters of treated participants responded to PST or ADT. This encouraging result is consistent with existing literature on the effectiveness of psychological interventions such as PST for people living with HIV (van Luenen, et al., The finding that the treatment response rate was higher among those receiving PST (83.3%), compared to those receiving ADT (66.7%), deserves future study. One potential explanation is that more participants had severe depression symptoms at the start of treatment in the ADT group (29%) than the PST group (5%). Both groups were receiving support through the Family Support Group program (see Online Supplement for description of this multi-session group program to support PMTCT and pregnancy management instituted by the Ugandan Ministry of Health) as part of usual care, but perhaps the PST sessions, which could be tailored to address the specific problems facing the patient, better equipped patients with skills to manage their depression and related stressors (Malouff, et al., For participants who did not respond to their initial treatment modality, providers made few changes to management (i.e., they were not “stepped up” in therapy intensity). In particular, of the 22 participants (10 on PST, 12 on ADT) who never responded to treatment, only five were switched (n = 1) or had another treatment modality added (n = 4) to improve response, although eight of these participants (four on each modality) prematurely discontinued treatment, thus having less time to experience a change in treatment. While PST could be intensified by adding sessions, there were no dosage increases among participants receiving ADT. These results suggest a need to strengthen the provision of supportive supervision and consider refresher trainings for providers, as prior studies have documented the importance of these supports for maintaining skills over time and ensuring fidelity to treatment protocols (Murray, et al., Limited research exists on factors influencing response to depression treatment in this population. However, our observations that greater social support and less intimate partner violence were associated with greater likelihood of treatment response are consistent with a prior Ugandan study (Atuhaire, et al., This study has limitations. We do not have data on decision-making around selection of initial depression treatment modality, nor fidelity to interventions (e.g., adherence to ADT, engagement in PST sessions), which could affect treatment response. In addition, due to sample size, we could not examine differential effectiveness of treatment modalities by depression severity. Lastly, the treatment efficacy data presented reflect response to open treatment; the comparison to usual care is presented elsewhere in the context of intervention effects on PMTCT outcomes, for which depression outcomes were a mediator (Wagner et al., submitted).These results highlight that non-mental health experts, specifically nurses and lay persons, can effectively identify depression and implement both psychological and pharmacologic evidence-based depression treatment with training and supervision by specialists. Nearly all participants who needed treatment received the treatment of their choice (predominantly PST), and nearly three-quarters responded to treatment, which is at least equivalent to response rates in the literature. Our data also demonstrate the importance of screening for social support and IPV to identify PWLWH at risk for or in need of treatment for perinatal depression. These findings will help inform efforts to strengthen the provision of evidence-based, individualized perinatal depression care to PWLWH in Uganda and other low resource settings. | PMC10564822 | |
Acknowledgements | The authors wish to thank the study participants and the study coordinators. They also thank Hilary Peterson and Mahlet Gizaw for their assistance with preparing this manuscript for submission. Research reported in this publication was supported by the National Institute of Mental Health (NIMH) of the National Institutes of Health under award number R01-MH115830 (Wagner). The content is solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. | PMC10564822 | ||
Author Contributions | Faherty: Conceptualization; Writing-Original Draft; Formal Analysis; Gwokyalya: Formal Analysis; Investigation; Data Curation; Writing-Review and Editing; Project Administration; Dickens: Writing-Review and Editing; Supervision; McBain: Writing-Review and Editing; Ngo: Writing-Review and Editing; Nakigudde: Writing-Review and Editing; Nakku: Writing-Review and Editing; Mukasa: Writing-Review and Editing; Beyeza-Kashesya: Writing-Review and Editing; Wanyenze: Conceptualization, Supervision, Funding Acquisition, Writing-Review and Editing; Wagner: Conceptualization, Supervision, Funding Acquisition; Writing-Review and Editing. | PMC10564822 | ||
Funding | Open access funding provided by SCELC, Statewide California Electronic Library Consortium. Research reported in this publication was supported by the National Institute of Mental Health (NIMH) of the National Institutes of Health under award number R01-MH115830 (Wagner). The content is solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Clinical Trials Registration Number: NIH Clinical Trial Registry NCT03892915 (clinicaltrials.gov). | PMC10564822 | ||
Data Availability | Study data may be made available upon request. | PMC10564822 | ||
Code Availability | N/A. | PMC10564822 | ||
Declarations | PMC10564822 | |||
Conflicts of interest | The authors declare no conflicts of interest. | PMC10564822 | ||
Ethics Approval | The study protocol was approved by the institutional review boards of the RAND Corporation and Makerere University School of Public Health and the Uganda National Council for Science and Technology. | PMC10564822 | ||
Consent to Participate | Participants provided written consent. | PMC10564822 | ||
Consent for Publication | N/A. | PMC10564822 | ||
References | PMC10564822 | |||
Subject terms | affective valence | ADVERSE EVENTS, EVENTS, EVENT | Previous studies have shed light on the importance of affect in risk perception and the role of mental imagery in generating affect. In the current study, we explore the causal relationship between mental imagery, affect, and risk perception by systematically varying the level of mental imagery in three levels (i.e., enhanced, spontaneous, or prevented). In light of the increasing environmental risk of adverse events caused by climate change, we operationalize risk as participants' perceived risk of climate change. One-thousand-fifty-five participants were recruited online and randomized to one of three levels of mental imagery. As predicted, we found a causal link between the level of mental imagery, affective experience, and perceived risk of climate change, in that enhanced mental imagery caused a larger decrease in positive affective valence and a larger increase in perceived risk of climate change. We argue that mental imagery enhances the negative affect associated with the risk event by creating a perceptual experience that mimics seeing the environmental risk events.Open access funding provided by Linköping University. | PMC10284903 |
Introduction | EVENTS | Every day we face different risks, everything from driving in traffic to societal issues like climate change. But what determines how we act in the face of these risks? Why do we sometimes take a leap of fate (i.e., risk seeking), and other times take the safe route (i.e., risk aversive)? The last couple of decades has shed light on the enormous importance of affect in how we perceive riskClimate change is an ongoing crisis that poses several risks for individuals and society. Risky environmental events are already at a high level and are only predicted to increase over the coming decadesThroughout the affect-as-information and risk-as-feelings literature, imagery (both pictorial and mental) has often been stipulated to be important for activating risk-associated affectsAlthough mental imagery has been suggested to impact our affects and subsequent risk perception, few studies have attempted to show a causal relationship between imagery, affect, and risk perceptionBeyond extending the understanding of the causal relationship between mental imagery, affective experience, and risk to a new context (i.e., climate change), our methodology differs from previous research concerning both experimental manipulation and control conditions. The current study manipulates mental imagery into three levels (1) by not specifying how to process the presented environmental events (i.e., spontaneous imagery), or (2) prompting participants to create vivid mental images of the events (i.e., enhanced mental imagery), or (3) preventing vivid mental images through a visuospatial interference task (i.e., prevented mental imagery).In our enhanced mental imagery condition, we aim for a methodology that creates vivid multimodal mental images. Previous studies have used free or semantic associationsIn the current study, we instead use a prevented mental imagery condition, utilizing visuospatial interference, which benefits from the limited resources of working memory | PMC10284903 | |
Research questions and hypotheses | Specially, we aim to answer if mental imagery impacts the perceived risk of climate change; and, in addition if mental imagery is a step in the causal relationship between affective experiences and climate change related risk perception. We expected that the magnitude of the change in the dependent variables (perceived risk, affective valence and arousal) from pre-manipulation to post-manipulation too be dependent on condition. Specifically, we expected that:Enhancing mental imagery would lead to a within-subject increase in perceived risk concerning climate change, from pre-manipulation to post-manipulation, that were of larger magnitude compared to both the spontaneous and prevented use of mental imagery (i.e., significant interaction effects).Preventing mental imagery would lead to a within-subject decrease in the magnitude of change in perceived risk concerning climate change, from pre-manipulation to post-manipulation, compared to both the spontaneous and enhanced use of mental imagery (i.e., significant interaction effects).Enhancing mental imagery would lead to a within-subject decrease in the level of positive affective valence and a within-subject increase in the level of arousal, from pre-manipulation to post-manipulation, that were of larger magnitudes compared to both the spontaneous and prevented use of mental imagery (i.e., significant interaction effects).Preventing mental imagery would lead to different magnitudes of change in the within-subject level of positive affective valence and arousal from pre-manipulation to post-manipulation, compared to both the spontaneous and enhanced use of mental imagery (i.e., significant interaction effects [All hypotheses were somewhat altered from the pre-registration to clarify that we expected to find interaction effects]). | PMC10284903 | ||
Method | PMC10284903 | |||
Participants | Informed consent was collected from all participants. According to guidelines from the Swedish research council concerning the Ethical Review of Research Involving Humans (SFS 2003:460), approval from an ethics committee is not required for behavioral research such as this study.Data from a total of 1055 participants were collected. Due to exclusions (not completing the full experiment (The participants (39.8% female, 58.6% male, 1% non-binary/third gender, 0.6% prefer not to say; no difference between conditions, An a priori power analysis was conducted using G*Power, the expected sample size ( | PMC10284903 | ||
Procedure and materials | PMC10284903 | |||
Pre-manipulation measures | EVENTS, EVENT, POSITIVE | After giving consent and completing demographic variables, all participants rated the three dependent variables, perceived risk of climate change, and their affective experience in the form of valence, and arousal.The main dependent variable is the perceived risk of climate change posed to oneself (two items), to others (two items), and to non-human populations on earth (two items), with six items in total on a visual analogues scale (VAS scale) ranging from 0 (Climate change does not present any risk) to 100 (Climate change presents an extreme risk).Valence was measured using a single item assessing the participants' level of pleasantness. Arousal was also measured with a single item assessing their level of activation. Participants first read a text explaining both the valence scale and arousal scale and then answered the question, “How do you feel right now?” For valence, participants answered on a VAS scale ranging from 0 (Negative) to 100 (Positive), for arousal they answered on a VAS scale ranging from 0 (Low activation) to 100 (High activation).After the pre-manipulation ratings, the participants were randomized to one of three conditions: (1) spontaneous mental imagery (control), (2) enhanced mental imagery, and (3) prevented mental imagery (the time spent on the experiment varied between conditions, Participants in the spontaneous mental imagery condition (control) first read “On the coming pages you will be presented with environmental events that could happen. Please read each environmental event carefully and then move to the next page and answer the questions.” Following this they were presented with an environmental risk event (i.e., water pollution increasing), but received no further instruction on how to process it and were then asked to rate their, valence, arousal, and vividness of their mental images of the environmental risk event. The vividness of mental imagery measure read “How clearly did you see the The spontaneous mental imagery condition (control) was designed to simulate turning people’s attention towards an environmental risk in day-to-day life. Even though we did not specify how to process the environmental risk events, we expect that the manipulation would activate some mental imagery processes. Although the prevalence and intensity of spontaneous mental imagery varies in the population | PMC10284903 | |
Enhanced mental imagery task | EVENT | Participants in the enhanced mental imagery condition were presented with an environmental risk event and were then instructed to create a mental image of that risk, “[example water pollution increasing] Now, please build up a very vivid image of a lake, the sea, or a river, using all your senses. Please imagine before your mind’s eye that this place is filled with trash and debris…” (Material adapted | PMC10284903 | |
Visuospatial working memory interference task | EVENTS, EVENT | Participants in the prevented mental imagery condition were presented with an environmental risk event and then partook in a mental rotation task, that served the purpose of visuospatial working memory interference. The mental rotation task consisted of completing five mental rotation items. Participants received a tutorial before starting the mental rotation task. They also rated their valence, arousal, and vividness of mental imagery after the mental rotation task for each environmental risk. The procedure was completed for all four environmental risk events. | PMC10284903 | |
Post-manipulation ratings | donation behavior | Following this, all participants rated the dependent variables again and completed some exploratory measures; pro-environmental donation behavior; pro-environmental intention; pro-environmental impact-belief; anticipated warm glow; severity of environmental risks presented in the study; personal knowledge of the place imagined (for the complete survey, see Open Science Framework). Participants pro-environmental intention was measured with eight items, for example, “How likely is it that you will hang all your clothes on a clothesline, the next time you wash your clothes?”, and answered on a visual analogue scale- (VAS) scale ranging from 0 (Much more likely that I would do the non-environmental behavior (e.g., put them in the tumble dryer) to 100 (Much more likely that I would do the pro-environmental behavior). Their pro-environmental impact beliefs were also measured for the same eight behaviors as in the intention measure, participants answered “How environmentally effective do you think it would be to dry all your clothes on a clothesline rather than putting them in a dryer?” The participants rated all items on a VAS scale ranging from 0 (Will not make any difference at all) to 100 (Will make an extremely big difference).Participants' responses to the manipulation check and their vividness ratings both indicate that the extent of mental imagery used, and the vividness of mental images created, are in line with what was expected from our manipulations (see supplementary | PMC10284903 | |
Results | For the main analyses on perceived risk, an aggregated measure of perceived risk was used (Mean values for perceived risk, affective valence, and affective arousal, presented for pre- and post-manipulation, split per condition.The risk perception values presented are based on the average value at each time. The values in brackets are the standard deviation. The 95% confidence intervals (CI) are calculated using bootstrapping (10 000 samples). Table Mean values for perceived risk, affective valence, and affective arousal, presented for pre- and post-manipulation, split per condition. Mean perceived risk presented on different scales (see y-axis) from the mean valence and mean arousal. The values presented for perceived risk are based on the average value at each time. Error bars represent the standard error. This figure includes all participants that were used in the main analysis ( | PMC10284903 | ||
Perceived risk of climate change | EVENT | We expected that enhancing mental imagery would lead to an increase in the perceived risk of climate change, that were of larger magnitude compared to both the spontaneous and prevented use of mental imagery (1). Subsequently, we also expected that preventing mental imagery would decrease the magnitude of change in perceived risk concerning climate change, compared to both the spontaneous and enhanced use of mental imagery (2). To test these hypotheses, we used split-plot ANOVAs 3 (condition) × 2 (time) to examine between- and within-subject differences, with planned comparisons. To answer our hypotheses our main interest was the interaction effects between condition and time, to see if the magnitude of the change in the variables is different depending on the condition (see Table Split-plot ANOVAs 3 (condition) × 2 (time) with planned comparisons.The risk perception values presented are based on the average value at each time. Table Comparing perceived risk in all three conditions revealed a significant main effect of time, participants perceived the risk to be more severe post-manipulation than pre-manipulation, no main effect of condition was identified. However, the expected interaction effect between condition and time was significant, indicating that the change in perceived risk varied in strength between the conditions. When comparing the conditions level for perceived risk post-manipulation with a simple main effect analysis (Sidak), no difference was found between either the control and enhanced condition (To explore the interaction effect further, we conducted our planned comparisons, first between the spontaneous mental imagery condition (control) to the enhanced condition. We again found a significant main effect of time, no main effect of condition, and a significant interaction effect. Although both the control and enhanced condition increased perceived risk of climate change after exposure to environmental risk event cues, the enhanced mental imagery increased perceived risk more than the control condition as hypothesized.Subsequently, we conducted our second planned comparison, between the spontaneous mental imagery condition (control) and the prevented condition. We again found a significant main effect of time, no main effect of condition, and an interaction effect. Again, both the control and prevented condition increased perceived risk of climate change, but as hypothesized the prevented mental imagery condition increased the perceived risk less than the control condition.Lastly, we conducted our third planned comparison between the enhanced and prevented conditions, we once again found a significant main effect of time, no main effect of condition, and a significant interaction effect. In line with our hypotheses, our results show that the level of mental imagery impacts the perceived risk of climate change—the more mental imagery used, the more the perceived risk of climate change was increased. | PMC10284903 | |
Affective experience | PMC10284903 | |||
Valence | affective valence, affective valence and arousal | EVENTS | Concerning affective experience, we expected that enhancing mental imagery would lead to a decrease in the level of positive affective valence of larger magnitude and a increase in the level of arousal of a larger magnitude, compared to both the spontaneous and prevented use of mental imagery (3). Subsequently, we also expected that preventing mental imagery would lead to different magnitudes of change in positive affective valence and arousal, when compared to the control and enhanced mental imagery condition (4). To answer these hypotheses, we again used split-plot ANOVAs (separate for emotional valence and arousal), with planned comparisons. To see if the magnitude of the change in the variables were different depending on the condition, our main interest was again the interaction effects between condition and time for each affective measure.When comparing affective valence in all three conditions the results revealed a main effect of time, a main effect of condition, and an interaction effect. Thus, the results show that the participants level of positive valence decreased, however, as expected to different degrees in the different conditions. When comparing the conditions on reported valence post-manipulation with a simple main effect analysis (Sidak), no difference was found between the control and enhanced condition (When comparing valence in the spontaneous mental imagery condition (control) to the enhanced condition we found a main effect of time, no main effect of condition, but an interaction effect. The results indicate that although both conditions decreased in positive affective valence, this decrease was larger in the enhanced mental imagery condition.Similarly, when comparing the spontaneous mental imagery condition (control) to the prevented condition we found a main effect of time, a main effect of condition, and an interaction effect. The results show that although positive valence decreased in both conditions, it decreased less in the prevented imagery condition.Lastly, when comparing the enhanced and prevented conditions, we found a main effect of time, a main effect of condition, and an interaction effect. In line with our hypotheses, our results show that level of mental imagery used to process risky environmental events impacts the affective valence—the more mental imagery the participants used to process the events the more they decreased their positive affective valence. | PMC10284903 |
Arousal | When comparing affective arousal in all three conditions the results revealed a main effect of time, no main effect of condition, however an interaction effect. Thus, the results indicate that the participants change in arousal level are dependent on the condition. When comparing the conditions on the reported arousal post-manipulation with a simple main effect analysis (Sidak), no difference was found between the control and enhanced condition (When comparing the level of arousal in the spontaneous mental imagery condition (control) to the enhanced condition we found no main effect of time, no main effect of condition, and no interaction effect. The results indicate that there was no significant change in arousal in either the spontaneous mental imagery condition (control) or the enhanced condition. However, when comparing the spontaneous mental imagery condition (control) to the prevented condition we did find a main effect of time, and a main effect of condition, and an interaction effect. The results indicate that only the prevented mental imagery condition increased in level of arousal. Further supporting that only prevented condition changed the level of arousal, we found a main effect of time, no main effect of condition, but an interaction effect, when comparing the enhanced and prevented conditions. The results from the analyses show that only the prevented condition changed the affective arousal from pre-manipulation to post-manipulation, indicating that the mental rotation task, and not the mental imagery level led to the change in arousal level. In the pre-registration regarding hypothesis 4, we wrote that we did not specify a direction in affective arousal “direction not specified”. We did this because we were not sure if the task would be activating or de-activating. However, this was in some contradiction to hypothesis 3; since hypothesis 3 precedes hypothesis 4, we decided to remove this from the manuscript. This did not change the interpretation of the results since affective arousal did not seem to be changed by the level of mental imagery. | PMC10284903 | ||
Pro-environmental intention and impact belief | OSF | In addition to the main research question, we posed an additional question: Is there a relationship between perceived risk and behavioral intention and/or impact belief? Two additional exploratory research questions were posed in the pre-registration (see OSF), for analyses to answer these see the | PMC10284903 | |
Discussion | affective valence | EVENTS, EVENT | The literature on affect-as-informationOur results suggest that on average positive affect decreased and risk perception of climate change increased when processing the environmental risk events. However, in line with our hypotheses, we specifically find that an increased level of mental imagery was related to a larger decrease in positive affective valence and a higher increase in perceived risk of climate change. These results are in line with previous research showing a link between mental imagery, affect, and risk perception outside the domain of climate changeWe find no evidence that the mental imagery manipulation changed the intention to act pro-environmentally or the perceived impact of these behaviors. These results are in contrast with a study that identified a link between mental imagery, perceived risk of climate change, and pro-environmental intentions and behaviorOur null finding suggests that there may be limitations to interventions aiming to increase pro-environmental behavior by increasing the perceived risk. However, previous research suggests that focusing on the consequences, particularly the health consequences of climate change, could help motivate pro-environmental behavior and policy supportAlthough the methodology in the current study allowed us to look at mental imagery processing at different levels, there are some limitations. One such limitation is that the conditions were not time matched. Future studies should control for this to make sure that the effects on valence and perceived risk are not due to the amount of processing time. However, our results indicate that the effect of the manipulations is not a result of the amount of processing time, since the control condition (shortest duration) had higher perceived risk and negative affective valence compared to the prevented condition (middle duration), which would not be the case if processing time drove the interaction effect. Also, previous research on mood and affect shows that most induced affect declines after a few minutes (e.g., 4–7), rendering it unlikely that the more time spent in the enhanced mental imagery condition to explain our main findingsOur control condition in which we allow for spontaneous imagery processing has benefits in that it increases the ecological validity of the results. However, there are potential confounding factors in the control condition such as the lower effort needed in this condition. However, we do not believe lower effort in the control condition could explain our results. Using mental rotation as visual-spatial interference allowed us to experimentally switch on and off mental imagery processing of environmental risk eventsLastly, one could argue that mental imagery is difficult to separate from general affect associated with the risk, thus suggesting that our results only further support that affect is used as information in risk judgments. However, our findings show that the mental imagery manipulation was successful in inducing differentially vivid mental images related to the same environmental risks. Hence, like others, we argue that mental imagery can amplify affectTo conclude, our findings strengthen the support for a causal relationship between mental imagery, affective experience, and risk perception, specifically here in the context of climate change. We argue that mental imagery increases the affect associated with the risk event by creating a perceptual experience that mimics seeing the environmental risk events, and then accordingly generating affective responses that can serve as information when making affect-laden risk judgments. However, we failed to find a relationship between mental imagery and pro-environmental intention and impact beliefs. Our findings increase our understanding of how affect impacts risk perception, but future studies should investigate the possible implications of how changing risk perception through affective manipulations might impact environmental values and behavior. | PMC10284903 |
Supplementary Information | The online version contains supplementary material available at 10.1038/s41598-023-37195-w. | PMC10284903 | ||
Author contributions | The authors their confirm contribution to the paper as follows: study conception and design: H.K., E.A., D.V.; data collection: H.K.; analysis and interpretation of results: H.K., E.A., D.V.; draft manuscript preparation: H.K., E.A., D.V. All authors reviewed the results and approved the final version of the manuscript. | PMC10284903 | ||
Funding | Open access funding provided by Linköping University. Funding was provided by Svenska Forskningsrådet Formas (2020-02072). | PMC10284903 | ||
Data availability | The datasets generated during and/or analyzed during the current study are available in the Open Science Framework, | PMC10284903 | ||
Competing interests | The authors declare no competing interests. | PMC10284903 | ||
References | PMC10284903 | |||
Abstract | PMC9970867 | |||
Background | Hepatocellular carcinoma, malignancy, hepatocellular carcinoma, tumour | HEPATOCELLULAR CARCINOMA, HEPATOCELLULAR CARCINOMA, RECURRENCE, TUMOUR | Hepatocellular carcinoma is the sixth most common malignancy in the world. Major hepatectomy (resection of greater than or equal to three liver segments) is needed if a tumour is large or close to major blood vessels. Despite low mortality, open major hepatectomy is associated with high rates of tumour recurrence that limits survival. Laparoscopic major hepatectomy has been proposed as an alternative approach with potential oncological benefits. This study compares laparoscopic major hepatectomy with open major hepatectomy for hepatocellular carcinoma in a randomized trial. | PMC9970867 |
Methods | The Asia-Pacific multicentre randomized trial of laparoscopic | PMC9970867 | ||
Results and conclusion | hepatocellular carcinoma | HEPATOCELLULAR CARCINOMA | The AP-LAPO trial will determine whether laparoscopic major hepatectomy offers oncological benefits to patients with hepatocellular carcinoma compared with open major hepatectomy. | PMC9970867 |
Registration number | NCT04852211 ( | PMC9970867 | ||
Protocol version | HCC | AP-LAPO trial version 01 (1 December 2021)The AP-LAPO trial will be the first multicentre randomized trial evaluating the long-term oncological benefits of LMH for HCC. It provides level 1 evidence on the best surgical approach of major hepatectomy for HCC. | PMC9970867 | |
Introduction | tumours, malignancy, HCC | HEPATOCELLULAR CARCINOMA, TUMOURS | Hepatocellular carcinoma (HCC) is the sixth most common malignancy in the worldOpen major hepatectomy (OMH) (resection of greater than or equal to three liver segments) is indicated for large tumours (greater than 5 cm) that are centrally located and/or close to intrahepatic major vessels. OMH is associated with significant morbidity (about 30 per cent), though hospital mortality has been reduced to less than 5 per centLaparoscopic major hepatectomy (LMH) has become a feasible and effective approach for the surgical management of HCC | PMC9970867 |
Methods | The Asia-Pacific multicentre randomized trial of laparoscopic | PMC9970867 | ||
Eligibility criteria | tumours, tumour, HCC | TUMOURS, METASTASIS, TUMOUR | Surgical procedures will be carried out by senior hepatobiliary surgeons. According to the international standard for laparoscopic liver surgery, each surgeon will need to have performed at least 55 resections classified as LMH to be included in the studyInclusion criteria consist of: a diagnosis of HCC as defined by the EASLExclusion criteria involve: previous treatment for HCC (for example transarterial chemoembolization or chemotherapy) and tumours requiring combined hepatectomy and thermal ablation therapy. Patients will also be excluded at the time of surgery (dropout) if there is: bilobar liver involvement; unexpected portal vein invasion and peritoneal metastasis not identified at preoperative imaging; liver remnant smaller than expected; or in both laparoscopic and open groups where the operating surgeon decides to abort the procedure due to locally advanced tumour condition before starting the resection phase. The patient flow chart is shown in Patient flow chartLMH, laparoscopic major hepatectomy; OMH, open major hepatectomy | PMC9970867 |
Intervention | PENICILLIN ALLERGY | Preoperatively all patients will undergo: blood tests (complete blood count, liver and renal function, coagulation profile, serum All patients will receive prophylactic antibiotics (Augmentin (amoxicillin + clavulanate) (GlaxoSmithKline) 1.2 g intravenously for one dose or levofloxacin (Daiichi Sankyo) 500 mg intravenously for one dose in case of penicillin allergy) and proton pump inhibitor (pantoprazole (Takeda) 20 mg intravenously for one dose). The surgical intervention will be performed under general anaesthesia. | PMC9970867 | |
Interventions: LMH | tumour | PNEUMOPERITONEUM, TUMOUR | For the LMH group, the patient will be placed in a left semi-decubitus position. Pneumoperitoneum will be created by carbon dioxide insufflation and the intra-abdominal pressure maintained at 13–15 mmHg. In addition to the camera port (10 mm), two 12-mm and two 5-mm ports will be used and adjusted according to tumour location and extent of resection. Laparoscopic ultrasonography will be used to confirm tumour location and guide liver transection. The extent of resection will depend on tumour location. Cholecystectomy will be performed. The anterior approach for major hepatectomy will be routinely adopted | PMC9970867 |
Intervention: OMH | tumour | TUMOUR | For the OMH group, resection of the tumour will be performed as previously described | PMC9970867 |
Outcomes | PMC9970867 | |||
Primary outcome | The primary outcome is 2-year recurrence-free survival. | PMC9970867 | ||
Secondary outcomes | POSTOPERATIVE COMPLICATIONS | These include 30-day, 90-day, and in-hospital mortality, postoperative complications, quality of life, time to functional recovery, 2-year overall survival, 5-year overall survival, and recurrence-free survival. Surgical stress-related cytokines serum interleukin 6 (IL-6) and immunosuppressive acidic protein (IAP) will be measured before surgery and on postoperative days 1 and 7. Measurement of IL-6 and IAP levels will be performed by immunoassay using commercially available kits (MILLIPLEX | PMC9970867 | |
Measurements | blood loss, hypotension | BLOOD LOSS, EVENTS | Intraoperative: operative time (measured from time of skin incision to wound suturing); blood loss; blood transfusion volumes and other blood products (platelet concentrate, fresh frozen plasma); intraoperative major events (hypotension for greater than 20 min and use of inotropes); and laparoscopic to open conversion. The conversion is defined as the change of surgical approach during the resection phase of major hepatectomy, when the operating surgeon encounters technical difficulty. Patients undergoing conversion will be included in the laparoscopic group and be analysed on an ‘intention-to-treat’ basis.Postoperative: liver biochemistry and coagulation profile on postoperative days 1, 3, 7, and day of discharge; postoperative morbidities according to Clavien–Dindo classification | PMC9970867 |
Follow-up | intrahepatic recurrence | RECURRENCE | No adjuvant treatment will be used after surgery. All patients will be followed up every 3–6 months for up to 5 years after operation. Follow-up assessment will include: liver function (clinical assessment of Child’s grade, complete blood count, liver, and coagulation profile); recurrence (based on serum Patients with intrahepatic recurrence will be managed by laparoscopic re-resection for the LMH group or open re-resection for the OMH group when considered feasible. For patients in whom re-resection is not possible, thermal ablation, transarterial chemoembolization, or salvage liver transplant will be offered according to the decision of the multidisciplinary team. | PMC9970867 |
Participant timeline | Data accrual will be performed prospectively using wed-based electronic case-report forms (eCRFs) according to the protocol plan (Schedule of enrolment, interventions, and assessments of patientsQoL, quality of life; LMH, laparoscopic major hepatectomy; OMH, open major hepatectomy. | PMC9970867 | ||
Sample size | Based on a reported 2-year recurrence-free survival rate of 72 per cent after OMH | PMC9970867 | ||
Recruitment | RECRUITMENT | All patients satisfying the inclusion and exclusion criteria will be offered recruitment into the trial. Investigators will provide information on possible advantages and disadvantages of the interventions. Patients will be included only after signing written informed consent ( | PMC9970867 | |
Randomization | Preoperative randomization will be adopted on the day of admission. A total of 330 subjects will be allocated 1:1 to either the LMH group or the OMH group. The randomization schedule will be generated by the Clinical Trials Centre (CTC) of the principal investigator’s centre, prior to the start of the study. Stratified block randomization (block size of 10) will be used to ensure treatment allocation in equal proportions at each centre. The randomization list will be kept in a set of tamper-evident envelopes. The envelopes will be identical and sealed. The trial identifier with a sequential number will be printed on each envelope. Envelopes will be unsealed to reveal the allocation treatment 1 day prior to surgery. | PMC9970867 | ||
Blinding | There will be no blinding for all recruited patients, investigators, operating surgeons, and other supporting staff. | PMC9970867 | ||
Statistical plan | tumour | SECONDARY, TUMOUR | The 2-year recurrence-free survival (primary outcome) and overall survival will be evaluated by Kaplan–Meier method and compared by the log rank test. Other secondary outcomes will be compared using the chi-squared test or Fisher’s exact test for categorical variables, and the Mann–Whitney All clinical data including patients’ demographics, operative details, tumour characteristics, and clinical outcome measure will be collected and centralized at the principal investigator’s centre using a password-protected web-based system to ensure confidentiality of personal information. Continuous clinical data monitoring will be performed by the principal investigator and co-investigators with the help of biostatisticians and research assistants. The data set will be kept confidential until the publication of trial results. | PMC9970867 |
Interim analyses | tumour | ADVERSE EVENTS, RECURRENCE, RECRUITMENT, TUMOUR | Patient recruitment status will be reviewed every 4 months in planned investigator meetings in which interim analyses will be carried out. If the accrual rate is slower than expected, the principal investigator and co-investigators will discuss the possible reasons and ways to improve the recruitment rate. The interim analyses will not be affected by the results. A data-monitoring group will consist of two independent, external experts who will be responsible for monitoring the progress of the study. If there are significantly more serious adverse events associated with either group after 1 year of commencement of the study, the trial will be terminated as decided by the principal investigator and the data-monitoring group. The same will be applied to the situation where the difference in tumour recurrence between groups is significantly less than expected. The final analysis of the trial will be carried out on an intention-to-treat basis. | PMC9970867 |
Ethics | An information sheet will be provided, and each subject will be given the opportunity to seek medical advice or to discuss the study with friends or family prior to involvement. Written informed consent will be mandatory for inclusion and patients will be free to withdraw it at any time. This study will be performed in accordance with the ethical standards of the Declaration of Helsinki of 1975 and its later versions. Ethics approval from the institutional review broad of each centre will be obtained. | PMC9970867 | ||
Dissemination plan | SECONDARY | The protocol of this trial has been registered in Clinicaltrials.gov. The final report on primary and secondary outcomes will be published upon the completion of 5-year follow-up. Both interim analysis and final analysis will be presented at local and international conferences. | PMC9970867 | |
Discussion | tumour, HCC | RECURRENCE, TUMOUR | The aim of the AP-LAPO trial is to test the hypothesis that LMH is associated with reduced surgical stress and immunosuppression compared with OMH resulting in lower tumour recurrence rates and better survival.OMH for HCC is associated with major morbidity of up to 40 per cent in high-volume centresRecent series have proven the feasibility and safety of LMH for HCCTo date, only retrospective studies using propensity score matching have compared LMH and OMH | PMC9970867 |
Trial status | RECRUITMENT | This trial received approval from the Joint Chinese University of Hong Kong—New Territories East Cluster Clinical Research Ethics Committee on 2 September 2020. The trial was registered at ClinicalTrials.gov of the US National Library of Medicine (registration no. NCT04852211) on 21 April 2021. The recruitment began in December 2021 and is anticipated to complete in November 2024. | PMC9970867 | |
Supplementary Material | Click here for additional data file. | PMC9970867 | ||
Funding | The AP-LAPO trial has received funding from the Health and Medical Research Fund of the Food and Health Bureau of Hong Kong Special Administrative Region of China (Project no. 08190446). The funder of the trial does not have an administrative role in study design, outcome analyses, writing of the report, or decision to submit the report. | PMC9970867 | ||
Disclosure | The authors declare no conflict of interest. | PMC9970867 | ||
Supplementary material | PMC9970867 | |||
Data availability | The data set will be kept confidential until the publication of trial results in an international journal. After that, the data set will be open upon an individual party’s request. | PMC9970867 | ||
References | PMC9970867 | |||
Key Points | PMC10122174 | |||
Question | esophageal cancer | OESOPHAGEAL CANCER | Is there an association between radiotherapy (RT) duration and clinical outcomes in patients with esophageal cancer receiving definitive chemoradiotherapy? | PMC10122174 |
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