Is laparoscopic excision for superficial peritoneal endometriosis helpful or harmful?:Protocol for a double-blinded, randomised, placebo-controlled, three-armed surgical trial

INTRODUCTION: Placebo-controlled surgical designs are recommended to ascertain treatment effects for elective surgeries when there is genuine doubt about the effectiveness of the surgery. Some elective surgeries for pain have been unable to show an effect beyond sham surgery, suggesting contributions from contextual factors. However, the nature of contextual factors in elective surgery is largely unexplored. Further, methodological difficulties in placebo-controlled surgical trials impact the ability to estimate the effectiveness of a surgical procedure. These include an overall lack of testing the success of blinding, absence of comparison to a no-surgery control group and dearth of test for neuropathic pain. For women with peritoneal endometriosis, there is uncertainty regarding the pain-relieving effect of surgery. Surgery may put patients at risk of complications such as postsurgical neuropathic pain, without guarantees of sufficient pelvic pain relief. The planned placebo-controlled trial aims to examine the effect of surgery on pelvic pain, widespread pain and neuropathic pain symptoms in women with peritoneal endometriosis, and to test the contribution of contextual factors to pain relief. METHODS AND ANALYSIS: One hundred women with peritoneal endometriosis will be randomised to either diagnostic laparoscopy with excision of endometrial tissue (active surgery), purely diagnostic laparoscopy (sham surgery) or delayed surgery (no-surgery control group). Outcomes include pelvic pain relief, widespread pain, neuropathic pain symptoms and quality of life. Contextual factors are also assessed. Assessments will be obtained at baseline and 1, 3 and 6 months postrandomisation. Mixed linear models will be used to compare groups over time on all outcome variables. ETHICS AND DISSEMINATION: The trial is approved by the Regional Ethics Committee in the Central Denmark Region (1-10-72-152-20). The trial is funded by a PhD scholarship from Aarhus University, and supported by a grant from ‘Helsefonden’ (20-B-0448). Findings will be published in international peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT05162794

What is the nocebo effect and does it apply to dentistry? : A narrative review

Background: Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual’s negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients’ negative expectations and the nocebo effect within dentistry. Aim: This review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented. Methods: A PubMed search was performed using keywords related to “nocebo,” “placebo,” “expectations,” and “dentistry.” In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields. Results: Although research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice. Conclusion: Preliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry

Nocebo response in dentistry : A systematic review and meta-analysis of adverse events in analgesic trials of third molar removal

Background: The nocebo response refers to the phenomenon where non-specific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Non-specific factors are also likely to influence AE occurrence following administration of active pharmacological treatments. Objective: This meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo- and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery. Methods: A systematic search was performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE ≥ 1) separately for the active and placebo arms. The proportion of patients with AE ≥ 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo- and active arm were calculated. Results: In 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE ≥ 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE ≥ 1 and drug-related dropouts. Conclusion: These results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon

WHAT IS THE NOCEBO EFFECT AND DOES IT APPLY TO DENTISTRY? A NARRATIVE REVIEW

BAGGRUND: På tværs af en lang række af medicinske fagområder vokser erkendelsen af noceboeffekten. Dette fænomen er karakteriseret ved utilstrækkelig behandlingseffekt, forværring af symptomer eller forekomst af bivirkninger som følge af patienters negative forventninger til diverse behandlinger. Indtil nu har der imidlertid ikke været særlig opmærksomhed på effekten af negative forventninger og nocebo inden for odontologien. FORMÅL: Denne oversigtsartikel opsummerer den væsentligste viden om fænomenet nocebo især i relation til smerte og administration af lægemidler. Desuden gives et overblik over den aktuelle evidens for nocebofænomenet i odontologisk sammenhæng. METODER: Der blev gennemført en søgning på PubMed med søgeordene “nocebo”, “placebo”, “expectations” og “dentistry”. Ud over de artikler, der blev fundet via søgningen, tilføjede forskere med særlig indsigt i placebo/nocebo eller odontologi vigtige referencer fra deres respektive fagområder. RESULTATER: Selvom noceboeffekten er sparsomt udforsket i relation til odontologien, tyder den tilgængelige evidens på, at faktorer, som hænger sammen med noceboeffekten, spiller en rolle i tandlægepraksis. KONKLUSION: Der er behov for yderligere udforskning af noceboeffekten inden for odontologien. På baggrund af vores almene viden om noceboeffekten kan man forvente interessante resultater i dette nye forskningsfelt.BACKGROUND: Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual’s negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients’ negative expectations and the nocebo effect within dentistry. AIM: This review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented. METHODS: A PubMed search was performed using keywords related to “nocebo”, “placebo”, “expectations” and “dentistry”. In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields. RESULTS: Although research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice. CONCLUSION: Preliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry

What is the nocebo effect and does it apply to dentistry? : A narrative review

Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual's negative treatment expectations, is growing across a multitude of medical fields. Within dentistry, little attention has been paid to patients' negative expectations, despite a number of studies supporting the influence of related factors, such as dental fear and anxiety, on the severity of peri- and post-operative dental pain. Only recently, a small number of commentaries and letters have emerged, urging dentists to recognise the possible existence of nocebo effects in dentistry and its implications for patient care. The present review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry

Nocebo response in dentistry : A systematic review and meta-analysis of adverse events in analgesic trials of third molar removal

BackgroundThe nocebo response refers to the phenomenon where non-specific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Non-specific factors are also likely to influence AE occurrence following administration of active pharmacological treatments. ObjectiveThis meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo- and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery. MethodsA systematic search was performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE >= 1) separately for the active and placebo arms. The proportion of patients with AE >= 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo- and active arm were calculated. ResultsIn 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE >= 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE >= 1 and drug-related dropouts. ConclusionThese results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon

Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies: the CoPPS Statement

Control interventions (often called “sham,” “placebo,” or “attention controls”) are essential for studying the efficacy or mechanism of physical, psychological, and self-management interventions in clinical trials. This article presents core recommendations for designing, conducting, and reporting control interventions to establish a quality standard in non-pharmacological intervention research. A framework of additional considerations supports researchers’ decision making in this context. We also provide a reporting checklist for control interventions to enhance research transparency, usefulness, and rigour