Medication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce... Show moreMedication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce. This proof-of-principle double-blind randomized clinical trial examined whether treatment effects in recent-onset rheumatoid arthritis (RA) can be optimized through pharmacological conditioning. After four months of standardized treatment (n = 46), patients in clinical remission (n = 19) were randomized to the Control group (C), continuing standardized treatment (n = 8), or the Pharmacological Conditioning (PC) group, receiving variable treatment according to conditioning principles (n = 11). After eight months, treatment was tapered and discontinued linearly (C) or variably (PC). Standard treatment led to large improvements in disease activity and HRQoL in both groups. The groups did not differ in the percentage of drug-free clinical remission obtained after conditioning or continued standard treatment. The PC group did show a larger decrease in self-reported disease activity (Cohen's d = 0.9) and a smaller increase in TNF-alpha levels (Cohen's d = 0.7) than the C group. During all phases, more differences between groups were found for the patients who followed protocol than for the intention-to-treat sample. Although the results are not conclusive, pharmacological conditioning may have some advantages in terms of disease progression and stability, especially during the conditioning phase, compared with standard clinical treatment. The effects may be particularly beneficial for patients who show a good initial response to increased medication dosages. Show less
This study investigated for the first time the effects of individual and combined application of 3 learning techniques (verbal suggestions, classical conditioning, and observational learning) on... Show moreThis study investigated for the first time the effects of individual and combined application of 3 learning techniques (verbal suggestions, classical conditioning, and observational learning) on placebo analgesia and extinction.Healthy participants (N = 206) were assigned to 8 different groups in which they were taught through either a verbal suggestion, a conditioning paradigm, a video observing someone, or any combination thereof that a placebo device (inactive transcutaneous electric nerve stimulation [TENS]) was capable of alleviating heat pain, whereas one group did not (control). Placebo analgesia was quantified as the within-group difference in experienced pain when the placebo device was (sham) 'activated' or 'inactivated' during equal pain stimuli, and compared between groups.Placebo analgesia was induced in groups with 2 or 3 learning techniques. Significantly stronger placebo analgesia was induced in the combination of all 3 learning techniques as compared to the individual learning techniques or control condition, underlining the additional contribution of 3 combined techniques. Extinction did not differ between groups. Furthermore, pain expectancies, but not state anxiety or trust, mediated placebo analgesia.Our findings emphasize the added value of combining 3 learning techniques to optimally shape expectancies that lead to placebo analgesia, which can be used in experimental and clinical settings. Perspective: This unique experimental study compared the individual versus combined effects of 3 important ways of learning (verbal suggestions, classical conditioning, and observational learning) on expectation-based pain relief. The findings indicate that placebo effects occurring in clinical practice could be optimally strengthened if healthcare providers apply these techniques in combination.(R) 2023 The Author(s). Published by Elsevier Inc. on behalf of United States Association for the Study of Pain, Inc This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Rationale & Objective: Patients with chronic kid-ney disease (CKD) not receiving dialysis, including kidney transplant recipients, often experience diffi-culties regarding self-management. An... Show moreRationale & Objective: Patients with chronic kid-ney disease (CKD) not receiving dialysis, including kidney transplant recipients, often experience diffi-culties regarding self-management. An important barrier for adherence to self-management recommendations may be the presence of psychological distress, consisting of depressive and anxiety symptoms. We investigated relationships between psychological distress and adherence to self-management recommendations. Study Design: Cross-sectional online question-naire data as part of the E-GOAL study. Setting & Participants: Patients with CKD (esti-mated glomerular filtration rate, 20-89 mL/min/ 1.73 m2) were recruited from April 2018 to October 2020 at 4 hospitals in The Netherlands and completed online screening questionnaires. Exposures: Psychological distress, depressive symptoms, and anxiety symptoms. Outcomes: Dietary adherence, physical activity, medication adherence, smoking, body mass index, and a CKD self-management index (ie, the sum of 5 binary indicators of nonadherence to the recommended self-management factors). Analytical Approach: Adjusted multivariable regression and ordinal logistic regression analyses. Results: In our sample (N = 460), 27.2% of pa-tients reported psychological distress, and 69.8% were nonadherent to 1 or more recommendations. Higher psychological distress was significantly associated with poorer dietary adherence (3adj, -0.13; 95% CI, -0.23 to -0.0 4), less phys-ical activity (3adj, -0.13; 95% CI, -0.22 to -0.03), and lower medication adherence (3adj, -0.15; 95% CI, -0.24 to -0.05), but not with smoking and body mass index. Findings were similar for depressive symptoms, whereas anxiety was only associated with poorer dietary and medication adherence. Every 1-point higher psychological distress was also associated with a higher likelihood of being nonadherent to an accumulating number of different recommendations (adjusted OR, 1.04; 95% CI, 1.02-1.07). Limitations: Cross-sectional design, possible re-sidual confounding, and self-report. Conclusions: Many people with CKD experience psychological distress, of whom most have diffi-culties self-managing their CKD. Given the relationship between psychological distress and adherence to CKD self-management recommendations, behavioral interventions are needed to identify and treat psychological distress as a potential barrier to CKD self-management. Show less
Nadinda, P.G.; Laarhoven, A.I.M. van; Evers, A.W.M.; Maas, J.; Beugen. S. van 2023
Objective: eHealth interventions can improve the health outcomes of people with a low socioeconomic position (SEP) by promoting healthy lifestyle behaviours. However, developing and implementing... Show moreObjective: eHealth interventions can improve the health outcomes of people with a low socioeconomic position (SEP) by promoting healthy lifestyle behaviours. However, developing and implementing these interventions among the target group can be challenging for professionals. To facilitate the uptake of effective interventions, this study aimed to identify the barriers and facilitators anticipated or experienced by professionals in the development, reach, adherence, implementation and evaluation phases of eHealth interventions for people with a low SEP.Method: We used a Delphi method, consisting of two online questionnaires, to determine the consensus on barriers and facilitators anticipated or experienced during eHealth intervention phases and their importance. Participants provided open-ended responses in the first round and rated statements in the second round. The interquartile range was used to calculate consensus, and the (totally) agree ratings were used to assess importance. Results: Twenty-seven professionals participated in the first round, and 19 (70.4%) completed the second round. We found a consensus for 34.8% of the 46 items related to highly important rated barriers, such as the lack of involvement of low-SEP people in the development phase, lack of knowledge among professionals about reaching the target group, and lack of knowledge among lower-SEP groups about using eHealth interventions. Additionally, we identified a consensus for 80% of the 60 items related to highly important rated facilitators, such as rewarding people with a low SEP for their involvement in the development phase and connecting eHealth interventions to the everyday lives of lower-SEP groups to enhance reach.Conclusion: Our study provides valuable insights into the barriers and facilitators of developing eHealth interventions for people with a low SEP by examining current practices and offering recommendations for future improvements. Strengthening facilitators can help overcome these barriers. To achieve this, we recommend defining the roles of professionals and lower-SEP groups in each phase of eHealth intervention and disseminating this study's findings to professionals to optimize the impact of eHealth interventions for this group. Show less
Nocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy... Show moreNocebo effects are adverse treatment outcomes that are not ascribed to active treatment components. Potentially, their magnitude might be higher in patients with chronic pain compared to healthy controls since patients likely experience treatment failure more frequently. The current study investigated group differences in the induction and extinction of nocebo effects on pressure pain at baseline (N = 69) and 1-month follow-up (N = 56) in female patients with fibromyalgia and matched healthy controls. Nocebo effects were first experimentally induced via classical conditioning combined with instructions on the pain-increasing function of a sham transcutaneous electrical nerve stimulation device, then decreased via extinction. One month later, the same procedures were repeated to explore their stability. Results suggest that nocebo effects were induced in the healthy control group during baseline and follow-up. In the patient group, nocebo effects were only induced during follow-up, without clear group differences. Extinction was only observed during baseline in the healthy control group. Further comparisons of nocebo effects and extinction indicated no significant changes across sessions, possibly suggesting their overall magnitudes were stable over time and across groups. In conclusion, contrary to our expectations, patients with fibromyalgia did not have stronger nocebo hyperalgesia; instead, they might be less responsive to nocebo manipulations than healthy controls. Show less
Cardol, C.K.; Meuleman, Y.; Middendorp, H. van; Boog, P.J.M. van der; Hilbrands, L.B.; Navis, G.; ... ; Dijk, S. van 2023
Nocebo effects on pain are widely thought to be driven by negative expectations. This suggests that anticipatory processing, or some other form of top-down cognitive activity prior to the... Show moreNocebo effects on pain are widely thought to be driven by negative expectations. This suggests that anticipatory processing, or some other form of top-down cognitive activity prior to the experience of pain, takes place to form sensory-augmenting expectations. However, little is known about the neural markers of anticipatory processing for nocebo effects. In this event-related potential study on healthy participants (n = 42), we tested whether anticipatory processing for classically conditioned nocebo-augmented pain differed from pain without nocebo augmentation using stimulus preceding negativity (SPN), and Granger Causality (GC). SPN is a slow-wave ERP component thought to measure top-down processing, and GC is a multivariate time series analysis used to measure functional connectivity between brain regions. Fear of pain was assessed with the Fear of Pain Questionnaire-III and tested for correlation with SPN and GC metrics. We found evidence that both anticipatory processing measured with SPN and functional connectivity from frontal to temporoparietal brain regions measured with GC were increased for nocebo pain stimuli relative to control pain stimuli. Other GC node pairs did not yield significant effects, and a lag in the timing of nocebo pain stimuli limited interpretation of the results. No correlations with trait fear of pain measured after the conditioning procedure were detected, indicating that while differences in neural activity could be detected between the anticipation of nocebo and control pain trials, they likely were not related to fear. These results highlight the role that top-down processes play in augmenting sensory perception based on negative expectations before sensation occurs. Show less
Objective: The objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and... Show moreObjective: The objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls. Methods: Placebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures. Results: Intranasal insulin stabilized dropping glucose levels in patients (B = 0.03, SE = 0.02, p = .027) and healthy men (B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls (B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants (B = 0.31, SE = 0.09, p < .001). No effects were found on other measures. Conclusions: Placebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction.Trial Registration: Netherlands Trial Register, NL7783 Show less
ObjectiveThe objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and... Show moreObjectiveThe objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls.MethodsPlacebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures.ResultsIntranasal insulin stabilized dropping glucose levels in patients (B = 0.03, SE = 0.02, p = .027) and healthy men (B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls (B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants (B = 0.31, SE = 0.09, p < .001). No effects were found on other measures.ConclusionsPlacebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction. Show less
