Certainty of genuine treatment increases drug responses among intellectually disabled patients

Objective: To determine the placebo component of treatment responses in patients with intellectual disability (ID). Methods: A statistical meta-analysis comparing bias-corrected effect sizes (Hedges g) of drug responses in open-label vs placebo-controlled clinical trials was performed, as these trial types represent different certainty of receiving genuine treatment (100% vs 50%). Studies in fragile X, Down, Prader-Willi, and Williams syndrome published before June 2015 were considered. Results: Seventeen open-label trials (n = 261, 65% male; mean age 23.6 years; mean trial duration 38 weeks) and 22 placebo-controlled trials (n = 721, 62% male; mean age 17.1 years; mean trial duration 35 weeks) were included. The overall effect size from pre to post treatment in open-label studies was g = 0.602 (p = 0.001). The effect of trial type was statistically significant (p = 0.001), and revealed higher effect sizes in studies with 100% likelihood of getting active drug, compared to both the drug and placebo arm of placebo-controlled trials. We thus provide evidence for genuine placebo effects, not explainable by natural history or regression toward the mean, among patients with ID. Conclusions: Our data suggest that clinical trials in patients with severe cognitive deficits are influenced by the certainty of receiving genuine medication, and open-label design should thus not be used to evaluate the effect of pharmacologic treatments in ID, as the results will be biased by an enhanced placebo component

Testing the boundaries for expectation effects in health and disease

Expectations affect our physiology and clinical outcomes, however the boundaries for this modulation are poorly understood. The purpose of this thesis is to investigate minimal requirements to elicit expectation effects on health-related outcomes, using experiments and an independent patient data meta-analysis. More specifically, this thesis will build on three aspects that traditionally are considered important for the formation of expectation effects: conscious awareness (Study I), endogenous opioids (Study II) and face-to-face interaction with a health-care representative (Study III, Study IV). I will thus investigate expectation effects from neurobiology up to our interaction with the context around us. In study I the role of conscious awareness in pain processing was investigated in a non-clinical population (N=114) to see if expectations can shape pain even when the participant is not aware of getting noxious stimuli. This was done by assessing whether noxious heat given while asleep would lead to changes in pain ratings in a subsequent test-phase when awake. Two control experiments consisted of only the test-phase. The results showed that participants who had been getting noxious heat while they were sleeping, displayed the same pattern of heightened pain ratings (i.e., pain alarm response) as participants in the control conditions who had not been exposed to the noxious stimuli during sleep. In comparison, the awake condition rated all test-phase stimuli the same. The results emphasize how important expectations are for shaping pain perception. Study II investigated if endogenous opioids are necessary for placebo-like effects/conditional responding. Healthy participants (N=30) were randomized to naltrexone/placebo before a pain-cue conditioning, using pressure pain and functional magnetic resonance imaging (fMRI). Results show comparable conditioned analgesic (pain relieving) and hyperalgesic (pain enhancing) responses in participants with naltrexone or placebo. These findings indicate that full function of the endogenous opioid system during pain conditioning is not necessary for conditional responding. Study III investigated if placebo effects can be created through online communication. Healthy participants (N=30) were randomized to empathetic/neutral communication online where they learnt about a sham analgesic TENS machine (fake pain-relieving machine). After this, a placebo experiment face-to-face was performed, in which the communication was held to a minimum. Results showed that placebo effects were induced during online communication, both in the empathetic and the neutral condition. In Study IV expectation ratings and how they relate to treatment outcome in online and face-to-face psychological treatment were investigated in an individual patient data meta-analysis. Individual participant data from studies that randomized patients to online versus face-to-face psychological intervention and who administered the Credibility and Expectancy Questionnaire (CEQ) were analyzed. Results shows comparable effects of how expectation ratings predicted clinical outcomes post treatment between online and face-to-face treatments. These results suggest that pain processing such as pain alarm response is affected by conscious awareness, endogenous opioids are not necessary in all situations to create pain cue conditioning, placebo effects can be created through online communication and expectations seem to be just as important for online treatments as it is for treatments delivered face-to-face. In sum, these results challenge formerly known boundaries for expectation effects

Kosten och motionens betydelse relaterat till metabolt syndrom : en litteraturstudie

Introduktion: Metabolt syndrom är ett globalt växande sjukdomstillstånd som cirka 25 procent av världens befolkning lider av. Personer som är drabbade av metabolt syndrom löper två till tre gånger större risk att insjukna i hjärt- och kärlsjukdom. Syfte: Litteraturstudiens syfte var att belysa hur kost och motion påverkar hälsan i relation till personer med metabolt syndrom. Metod: Litteraturstudien har använt Polit och Beck (2012) niostegsmodell. Litteratursökningarna genomfördes i databaserna CINAHL och PubMed. Efter att urval och kvalitetsgranskning av artiklarna genomförts resulterade det i 11 kvantitativa artiklar som användes till litteraturstudiens resultat. Resultat: Litteraturstudiens resultat delades in i två huvudkategorier vilka var fysiologiska förändringar och psykologiska förändringar med tillhörande fem underkategorier påverkan på hjärt- och kärlsystemet, förändringar av provsvar, förändrad kroppssammansättning, förändrad prestationsförmåga och ökat välbefinnande. De här underkategorier innefattar hur deltagarnas hälsa har påverkats utifrån olika träningsmetoder och dieter. Slutsats: Studien visar på att fysisk aktivitet och diet bidrog till viktnedgång hos personer med metabolt syndrom vilket visade sig ge positiv hälsoutveckling av deltagarnas hälsa

Placebo Responses Among Men With Erectile Dysfunction Enrolled in Phosphodiesterase 5 Inhibitor Trials : A Systematic Review and Meta-analysis

Importance Placebo responses in the treatment of erectile dysfunction (ED) are poorly described in the literature to date. Objective To quantify the association of placebo with ED outcomes among men enrolled in placebo-controlled, phosphodiesterase 5 inhibitor (PDE5I) trials. Data Sources For this systematic review and meta-analysis, a database search was conducted to identify double-blind, placebo-controlled studies using PDE5Is for the treatment of ED published from January 1, 1998, to December 31, 2018, within MEDLINE, Embase, Cochrane Library, and Web of Science. Only articles published in the English language were included. Study Selection Double-blind, placebo-controlled randomized clinical trials of PDE5Is for ED were included. Studies were excluded if they did not provide distribution measures for statistical analysis. Study selection review assessments were conducted by 2 independent investigators. A total of 2215 studies were identified from the database search, and after review, 63 studies that included 12 564 men were analyzed. Data Extraction and Synthesis Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in abstracting data and assessing validity. Data were extracted from published reports by 2 independent reviewers. Quality assessment was performed using the Jadad scale. Data were pooled using a random-effects model. Main Outcomes and Measures The main outcome was improvement in the erectile function domain of the International Index of Erectile Function questionnaire in the placebo arm of the included studies. Effect size was reported as bias-corrected standardized mean difference (Hedges g). The hypothesis was formulated before data extraction. Results A total of 63 studies that included 12 564 men (mean [SD] age, 55 [7] years; age range, 36-68 years) were included. Erectile function was significantly improved among participants in the placebo arm, with a small to moderate effect size (Hedges g [SE], 0.35 [0.03]; P < .001). Placebo effect size was larger among participants with ED associated with posttraumatic stress disorder (Hedges g [SE], 0.78 [0.32]; P = .02) compared with the overall analysis. No significant difference was found between placebo and PDE5Is for ED after prostate surgery or radiotherapy (Hedges g [SE], 0.30 [0.17]; P = .08). Conclusions and Relevance In this study, placebo was associated with improvement of ED, especially among men with ED-related posttraumatic stress disorder. No difference was found between placebo and PDE5I among men treated for ED after prostate surgery

Placebo response and media attention in randomized clinical trials assessing cannabis-based therapies for pain: a systematic review and meta-analysis.

IMPORTANCE Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements. OBJECTIVE To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention. DATA SOURCES A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered. STUDY SELECTION Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders. DATA EXTRACTION AND SYNTHESIS The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model. MAIN OUTCOMES AND MEASURES Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g). RESULTS Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes. CONCLUSIONS AND RELEVANCE Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief