Psychometric evaluation of the modified quality of recovery score for the postanaesthesia care unit (QoR-PACU2)-A prospective validation study.

BACKGROUND: To date, there is no instrument to adequately assess self-reported quality of recovery (QoR) in the post-anesthesia care unit (PACU). We previously developed the QoR-PACU, a 13-item questionnaire specifically applicable to the PACU. The feasibility, acceptance, and validity of the QoR-PACU were promising. However, measures of reliability were slightly lower than expected. METHODS: We modified the QoR-PACU and evaluated its psychometric properties in a cohort of adult patients scheduled for non-cardiac surgery with general anesthesia. The modified QoR-PACU (termed QoR-PACU2) was administered before surgery and postoperatively in the PACU at the time of the decision to discharge. RESULTS: A total of 307 patients were included in the final analysis. Postoperative QoR-PACU2 sum scores differed across categories of sex, perioperative and surgical risk, and modes of airway management. The duration of anesthesia and surgery, maximum pain intensity and analgesic requirement in the PACU, and length of PACU stay were all inversely correlated with QoR in the PACU. Cronbach's alpha was 0.70 (95%CI: 0.66-0.75). The intra-class correlation coefficient was 0.86 (95%CI: 0.70-0.94, p < 0.001) for intra-rater reliability (n = 24) and 0.94 (95%CI 0.90 to 0.97, p < 0.001) for inter-rater reliability (n = 31). Cohen's effect size was 0.68 and the standardized response mean was 0.57. CONCLUSION: The QoR-PACU2 assesses self-reported QoR after surgery in the PACU. Measures of feasibility, validity, and reliability were consistently high. Measures of responsiveness were moderate, which might be attributable to the heterogeneity of the study population. Future studies should include aspects of ethnicity and cross-cultural applicability.

Can open label placebos improve pain and gluten tolerance via open label placebos in fibromyalgia patients? A study protocol for a randomised clinical trial in an outpatient centre.

INTRODUCTION: Fibromyalgia syndrome (FMS) is defined as a medical condition with chronic widespread musculoskeletal pain accompanied by mood disorders, fatigue and sleep disturbances. Treatment of this condition can often be challenging. As nutrition in general and nutritional interventions in the context of illness management become more and more important, current research also focuses on the relevance of diets for FMS, including gluten as field of interest. To date, there is no clear evidence that a gluten-free diet or other nutritional interventions are significantly important for the reduction of pain in the context of FMS. Only a very few studies show that FMS patients respond to a gluten-free diet and that cytokine production (also in FMS) can be reduced through the change. However, these studies have not investigated whether and to what extent cognitive factors, such as the expectation of symptom reduction triggered by diet, play a role. Recent research shows that treatment expectation plays an important role in the course of the disease and in the effectiveness of treatment approaches. For example, there are promising pain treatment options using open-label placebos (OLPs), which show that expectation alone, rather than the pharmacological substance of medication, can reduce pain experience. In our study protocol, we hypothesise that treatment expectation can be positively influenced by the given information regarding the placebos, resulting in improved treatment outcomes for pain and indigestions. METHODS AND ANALYSIS: In this trial, patients with FMS will undergo a food challenge and take an OLP (patients will be informed about the placebo), followed by a 3-week OLP treatment. The subjects will be randomised into four groups: (a) gluten-free porridge+neutral OLP instructions; (b) gluten-free porridge+positive OLP instructions; (c) gluten-containing porridge+neutral OLP instructions and (d) gluten-containing porridge+positive OLP instructions. Patients will be recruited via different institutions and support groups in Hamburg. The inclusion criteria are (a) diagnosed FMS, (b) absence of wheat allergy, coeliac disease or pain-related red flags and (c) being a minimum age of 18 years. The study requires 100 subjects to assess the primary outcomes: pain intensity and occurence of indigestion. Secondary outcomes are functional capacity, treatment expectation, and different pain-related and inflammation-related blood parameters. The measure time points will be before and after the food challenge and before and after the 3-week OLP treatment. ETHICS AND DISSEMINATION: Ethical approval was obtained in October 2021 from the Hamburg Medical Ethics Council. The results of the study will be disseminated through publications, presentations and conference meetings. TRIAL REGISTRATION NUMBER: German Clinical Trials Register (DRKS; DRKS00027130).

Psychometric evaluation of a quality of recovery score for the postanesthesia care unit-A preliminary validation study.

INTRODUCTION: Patients' perception of postoperative recovery is a key aspect of perioperative care. Self-reported quality of recovery (QoR) has evolved as a relevant endpoint in perioperative research. Several psychometric instruments have been introduced to assess self-reported recovery 24 hours after surgery. However, there is no questionnaire suitable for use in the postanesthesia care unit (PACU). We aimed to develop and psychometrically evaluate a QoR questionnaire for the PACU (QoR-PACU). METHODS: The QoR-PACU was developed in German language based on the 40-item QoR-40 questionnaire. Between March and November 2020, adult patients scheduled for elective urologic surgery completed the QoR-PACU preoperatively and during the PACU stay. We evaluated feasibility, validity, reliability, and responsiveness. RESULTS: We included 375 patients. After two piloting phases including 72 and 48 patients, respectively, we administered the final version of the QoR-PACU to 255 patients, with a completion rate of 96.5%. Patients completed the QoR-PACU at a median of 125.0 (83.0; 156.8) min after arrival in the PACU. Construct validity was good with postoperative QoR-PACU sum scores correlating with age (r = 0.23, 95% CI: 0.11 to 0.35, p < 0.001), length of PACU stay (r = -0.15, 95%CI: -0.27 to -0.03, p = 0.02), pain in the PACU (r = -0.48, 95% CI: -0.57 to -0.37, p < 0.001) and piritramide dose administered (r = -0.29, 95% CI: -0.40 to -0.17, p < 0.001). Cronbach's alpha was 0.67 (95% CI: 0.61-0.73) with moderate test-retest reliability (ICC of 0.67, 95% CI: 0.38 to 0.83). Cohen's effect size was 3.08 and the standardized response mean was 1.65 indicating adequate responsiveness. CONCLUSION: The assessment of QoR in the early postoperative period is feasible. We found high acceptability, good validity, adequate responsiveness, and moderate reliability. Future studies should evaluate the psychometric properties of the QoR-PACU in more heterogeneous patient populations including female and gender-diverse patients with varying degress of perioperative risk.

Nocebo Hyperalgesia in Patients With Fibromyalgia and Healthy Controls: An Experimental Investigation of Conditioning and Extinction Processes at Baseline and 1-Month Follow-up.

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 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. PERSPECTIVE: The current study is the first to investigate group differences in experimentally manipulated nocebo hyperalgesia between chronic pain and healthy populations at baseline and 1-month follow-up. Since nocebo effects are common in clinical settings, their investigation in different populations is essential to explain and minimize their adverse effects during treatment.

[Psychosocial factors in pain and pain management : A statement]. / Psychosoziale Faktoren bei Schmerz und Schmerzbehandlung : Eine Positionsbestimmung.

Although psychosocial factors have a profound impact on the experience of pain and pain recovery, the transfer to clinical application has so far been insufficient. With this article, a task force of the special interest group "Psychosocial Aspects of Pain" of the German Pain Society (Deutsche Schmerzgesellschaft e. V.) would like to draw attention to the considerable discrepancy between existing scientific evidence on the importance of psychosocial factors in the development of chronic pain disorders and the translation of these findings into the care of pain patients. Our objective is a stronger integration of psychological and psychosomatic expertise in pain treatment and research, as well as the improvement of structural and institutional conditions, to achieve an increased consideration of psychosocial aspects. In this way, modern, integrative and complex pain concepts can reach the patient. Based on these fundamental findings on the importance of psychosocial factors in pain and pain treatment, implications for the transfer to clinic and further research will be shown.

A digital application and augmented physician rounds reduce postoperative pain and opioid consumption after primary total knee replacement (TKR): a randomized clinical trial.

BACKGROUND: Severe postoperative pain not only is a considerable burden for patients but also leads to overprescription of opioids, resulting in considerable health concerns. The remarkable development of new technologies in the health care system provides novel treatment opportunities in this area and could exploit the additional placebo effect, provide added value for patients, and at the same time support hospital staff. We aimed to test the pain- and opioid intake-reducing effects of enhanced postoperative pain management by boosting pain medication by using a technical application and/or augmented physician rounds. METHODS: In a four-arm, randomized clinical trial, 96 patients (24 patients per group) scheduled for a total knee replacement (TKR) were randomized into four groups for four postoperative days: an "application" group (APP) with information via an iPad-based application; a "doctor" group (DOC) with augmented physician rounds; a combination group (APP+DOC), which received both interventions; and a "treatment as usual" group (TAU) as a baseline with no additional intervention besides the standard care which consists of standardized medication, regular physician rounds, and physiotherapy. Postoperative pain and opioid requirements pre- and postoperatively until hospital discharge were recorded. RESULTS: The difference between post- and preoperative pain was significantly different between the groups (P=.02, partial η2=.10). APP+DOC experienced greater postoperative pain relief than DOC (mean: 2.3 vs. 0.7, 95% CI: 0.08-3.09; P=.04) and TAU (mean 2.3 vs. 0.1; 95% CI: 0.69-3.71; P=.005), respectively, the difference compared to APP (mean 2.3 vs. 1.7; 95% CI -1.98-1.76) was not significant. Opioid consumption differed significantly between groups (P=.01, partial η2=.12). APP+DOC (72.9 mg) and DOC (75.4 mg) consumed less oxycodone than APP (83.3 mg) and TAU (87.9 mg; 95% CI: 2.9-22.1; P=.003). APP+DOC consumed significantly less oxycodone than DOC (d=0.2-0.4). There were no significant group differences in NSAID and Morphine sulfate consumption. Patients in APP+DOC were more satisfied with their treatment than patients in TAU (P=.03, partial η2=.09). CONCLUSIONS: The combination of an innovative digital app, which implements open drug administration and augmented physician rounds that support the doctor-patient relationship can significantly improve postoperative pain management. TRIAL REGISTRATION: The protocol was approved by the local ethics committee of the ethical commission of the German Psychological Society (Deutsche Gesellschaft für Psychologie; DGPs). The study was registered at DRKS.de (identifier: DRKS00009554).

The Influence of Preoperative Mood and Treatment Expectations on Early Postsurgical Acute Pain After a Total Knee Replacement.

Background: Reducing postoperative pain immediately after surgery is crucial because severe postoperative pain reduces quality of life and increases the likelihood that patients develop chronic pain. Even though postoperative pain has been widely studied and there are national guidelines for pain management, the postoperative course is differently from one patient to the next. Different postoperative courses could be explained by factors related to the treatment context and the patients. Preoperative emotional states and treatment expectations are significant predictors of postoperative pain. However, the interaction between emotional states and preoperative treatment expectations and their effect on postoperative pain have not yet been studied. The aim of our study was to identify the interaction between emotional states, treatment expectation and early postsurgical acute pain. Methods: In this prospective clinical trial, we enrolled patients who had received a TKR at a German hospital between October 2015 and March 2019. Patients rated their preoperative pain on a numeric rating scale (NRS) 0-10 (0 = no pain and 10 = worst pain imaginable), their emotional states preoperatively on the Pain and State of Health Inventory (PHI), their preoperative treatment expectations on the Stanford Expectation of Treatment Scale (SETS), and their postoperative level of pain on a NRS 0-10. Findings: The questionnaires were completed by 122 patients (57% female). Emotional states predict negative treatment expectation F(6, 108) = 8.32, p < 0.001, with an excellent goodness-of-fit, R2 = 0.31. Furthermore, a mediator analysis revealed that the indirect effects and therefore relationship between the emotional states sad (ab = 0.06, 95% CI[0.01, 0.14]), anxious (ab = 0.13, 95% CI[0.04, 0.22]), and irritable (ab = 0.09, 95% CI[0.03, 0.17]) and postoperative pain is fully mediated by negative treatment expectations. Whereas the emotional states tired (ab = 0.09, 95% CI[0.03, 0.17]), dizzy/numb (ab = 0.07, 95% CI[0.01, 0.20]), weak (ab = 0.08, 95% CI[0.03, 0.16] are partially mediated by negative treatment expectations. Conclusion: The relationship between emotional states and postoperative pain is mediated by negative treatment expectations. Therefore, innovative treatment strategies to reduce postoperative pain should focus on eliminating negative treatment expectation through establishing a differentiated preoperative expectation management program that also focuses on emotional states.

Observing treatment outcomes in other patients can elicit augmented placebo effects on pain treatment: a double-blinded randomized clinical trial with patients with chronic low back pain.

ABSTRACT: Clinical research on social observational learning (SoL) as an underlying mechanism for inducing expectancy and eliciting analgesic placebo effects is lacking. This double-blinded randomized controlled clinical trial investigated the influence of SoL on medication-augmenting placebo effects in 44 patients with chronic low back pain. Our hypothesis was that observing positive drug effects on pain and mobility in another patient could increase pain reduction and functional capacity. To test this, we compared the effects of observing positive treatment outcomes in a sham patient (the social learning group [SoLG]) vs hearing the same sham patient report neutral effects (the control group). In the SoLG, the sham patient told peers about pain reduction due to amitriptyline and demonstrated his improved mobility by bending forwards and sideways while he told the control group only that he was taking amitriptyline. The primary outcome was a reduction in clinical low back pain self-ratings. The secondary outcome was perceptions of pain-related disability. The exploratory outcome was mood and coping statements. Data collection occurred before and after the intervention and 2 weeks later. After the intervention, pain decreased in both groups (F [1, 41] = 7.16, P < 0.05, d = 0.83), with no difference between groups. However, the SoLG showed a significantly larger decrease in perceived disability (F [1, 41] = 5, P < 0.05, d = 0.63). The direct observation of patient with chronic low back pain of positive treatment outcomes in the sham patient seems to have enhanced the treatment effects while indirect verbal reports of reduced pain did not.

Optimising treatment expectations in chronic lower back pain through observing others: a study protocol for a randomised clinical trial.

INTRODUCTION: Chronic lower back pain (CLBP) is a frequent cause of medical consultations worldwide, and it results in decreased quality of life and disability. Current treatments for CLBP are often not effective, and alternatives are urgently needed. Three promising possibilities have emerged: (1) open-label placebo treatment reduces chronic pain, (2) placebo treatment is as efficacious as opioid treatment with a high correlation between patient expectation and treatment outcome, and (3) observing positive effects in another patient can improve functional capacity. We hypothesise that treatment expectations can be positively influenced through social observation and improve treatment outcome. METHODS AND ANALYSIS: In our clinical trial, we will randomise patients with CLBP into five groups. Two groups receive either a 3 week course of treatment with an analgesic (ANA) (metamizole/dipyrone) or with open-label placebos (OLP). For one of each group, we will build treatment expectations through observational learning and assess its impact on the treatment. For this purpose, one group each will watch either a positive or a neutral video. The intervention groups will be compared with a control group that will not be given any medication or observational learning. Participants will be recruited via all institutions in the Hamburg metropolitan area that treat patients with CLBP. Patients are eligible for inclusion if they are at least 18 years or older, have CLBP (of at least 3 months duration), and agree to potentially receive an active ANA or an OLP. Patients with pain-related "red flags" will be excluded. The study requires 150 participants (30 participants per group) to assess the differences in the primary outcome, pain intensity. Secondary outcomes include changes in treatment expectations, anxiety, comorbid depression, stress-related neuroendocrine measures, functional and structural connectivity, functional capacity, and ANA consumption. All outcomes and treatment expectations will be measured before and after the intervention and 3 months post-intervention. ETHICS AND DISSEMINATION: Ethical approval was obtained in January 2020 from the Hamburg Medical Ethics Council (ref number PV7067). Outcomes will be disseminated through publications in peer-reviewed journals and presentations at national and international conference meetings. TRIAL REGISTRATION NUMBER: The approved trial protocol was registered at the German Clinical Trials Register (DRKS) and can be found at drks.de (Identifier: DRKS00024418).

[Treatment expectations for postoperative pain]. / Behandlungserwartungen bei postoperativen Schmerzen.

BACKGROUND: Preoperative treatment expectations have a significant influence on postoperative pain and treatment outcomes. Positive expectations are an important mechanism of the placebo effect and negative expectations are an important mechanism of the nocebo effect. OBJECTIVES: What is the influence of treatment expectations, how are they assessed in the clinical setting, and how can the findings be implemented in clinical practice? METHODS: A literature search was performed using the keywords "expectation" AND ("postoperative" OR "surgery"). All English and German articles were selected. In addition, the bibliographies of the articles found were examined and incorporated. RESULTS: A total of 158 articles were found, 49 of which investigate expectations and include postoperative treatment outcomes. Most articles investigate expectations only at baseline to ensure that groups do not differ preoperatively. The studies that prospectively examine the influence of expectations apply very different measurement methods to investigate expectancy constructs. Thus, comparison across studies is difficult. There are few studies examining whether and how expectations can be influenced perioperatively, and who developed practice-relevant interventions to change them. CONCLUSION: Valid and reliable measurement tools should be applied in clinical trials for a more robust investigation of treatment expectations. Further studies should address possible intervention options so that treatment expectations can also be incorporated into standard clinical care.

The Impact of Surgery-Related Muscle Injury on Prevalence and Characteristics of Acute Postcraniotomy Headache - A Prospective Consecutive Case Series.

BACKGROUND: The latest third edition of the International Classification of Headache Disorders delineates diagnostic criteria for acute headache attributed to craniotomy (AHAC), but data on possible predisposing factors are sparse. This prospective observational study aims to evaluate the impact of surgery-related muscle incision on the prevalence, severity, and characteristics of AHAC. PATIENTS AND METHODS: Sixty-four consecutive adults (mean age: 54.2 ± 15.2 years; 26 males and 38 females) undergoing cranial neurosurgery for various reasons without preoperative headache were included. After regaining consciousness, all patients reported their average daily headache on a numeric pain rating scale (NRS; range: 0-10), headache characteristics, as well as analgesic consumption from day 1 to 3 after surgery. Three distinct patient cohorts were built with respect to the surgical approach (craniotomy ± muscle incision; burr hole surgery) and group comparisons were performed. Additionally, patients with AHAC ≥ 3 NRS were reevaluated at 7.2 ± 2.3 months following treatment by means of standardized questionnaires to determine the prevalence of persistent headache attributed to craniotomy as well as headache-related disability and quality of life. RESULTS: Thirty of 64 (46.9%) patients developed moderate to severe AHAC (NRS ≥ 3) after cranial neurosurgery. There were no significant group differences with regard to age, gender, or general health condition (American Society of Anesthesiologists Physical Status Classification). Craniotomy patients with muscle incision suffered from significantly higher early postoperative mean NRS scores compared with their counterparts without procedure-related muscle injury (3.4 ± 2.3 vs. 2.3 ± 1.9) as well as patients undergoing burr hole surgery (1.2 ± 1.4; p = 0.02). Moreover, the consumption of nonopioid analgesics was almost doubled following muscle-transecting surgery as compared with muscle-preserving procedures (p = 0.03). Young patient age (odds ratio/95% confidence interval for each additional year: 0.93/0.88-0.97) and surgery-related muscle injury (5.23/1.62-19.41) were identified as major risk factors for the development of AHAC ≥ 3 NRS. There was a nonsignificant trend toward higher pain chronification rate as well as headache-related disability after craniotomy with muscle injury. CONCLUSION: Surgery-related muscle damage may be an important predisposing factor for AHAC. Therefore, if a transmuscular approach is unavoidable, the neurosurgeon should be aware of the need for adequately adjusted intra- and postoperative analgesia in these cases.

[Systemic inflammation, "sickness behavior" and expectations : What role do expectations play in inflammation-associated symptoms?] / Systemische Entzündung, "Sickness Behavior" und Erwartungsprozesse : Welche Rolle spielen Erwartungen bei entzündungsassoziierten Symptomen?

BACKGROUND: Systemic inflammation is accompanied by unspecific physical and psychological symptoms of sickness, including pain and affective symptoms. These symptoms (commonly called "sickness behavior") are mediated by the central nervous effects of immune messengers such as pro-inflammatory cytokines. While adaptive during acute inflammation, sickness symptoms can have detrimental effects on quality of life during chronic inflammation and may contribute to comorbidity in chronic pain conditions. Despite the high clinical relevance of sickness behavior, psychological interventions aiming to modulate sickness symptoms have hardly been investigated. One approach could be the use of expectation effects, since positive and negative expectations (placebo or nocebo effects) have been shown to have an influence on pain and affect-related symptoms. OBJECTIVES: Herein, we summarize immunological and psychobiological factors that contribute to pain in the context of sickness behavior, with a major focus on findings from experimental endotoxemia. Against this background, we discuss how expectations could help to improve immune-mediated sickness symptoms and outline potential psychological and psychobiological mechanisms underlying this putative effect.

Development and Validation of the Pain and State of Health Inventory (PHI): Application for the Perioperative Setting.

Currently, general measurements and evaluations of the quality of recovery are difficult because no adequate measuring tools are available. Therefore, there is an urgent need for a universal tool that assesses patient-relevant criteria-postoperative pain, state of health, and somatic parameters. For this purpose, a pain and state of health inventory (PHI, Schmerz- und Befindlichkeitsinventar (SBI) in German) has been developed. In this study, we describe its development and validation. The development phase was led by an expert panel and was divided into three subphases: determining the conceptual structure, testing the first editions, and adjusting the inventory for a finalized edition. For the purpose of validation, the PHI was filled in by 132 patients who have undergone total knee replacement and was analyzed using principal component analysis. Construct validity was tested by correlating the items with validated questionnaires. The results showed that the inventory can test pain, state of health, and somatic parameters with great construct validity. Furthermore, the inventory is accepted by patients, map changes, and supports to initiate adequate treatment. In conclusion, the PHI is a universal tool that can be used to assess the quality of recovery in the perioperative setting and allow immediate intervention.

Targeted Use of Placebo Effects Decreases Experimental Itch in Atopic Dermatitis Patients: A Randomized Controlled Trial.

Evidence from pain research shows that the effectiveness of active pharmacological treatments can be enhanced by placebo effects. The "open drug administration" is superior to "hidden drug administration.​" In a randomized controlled trial, we aimed to show that the targeted use of placebo effects increases the efficacy of an antihistamine (dimetindene) infusion in participants with atopic dermatitis. We openly infused dimetindene (drug) in full sight with information (intervention group 1: OPEN-DRUG+INST), openly infused drug with an additional classical conditioning learning experience (intervention group 2: OPEN-DRUG+INST+COND) or infused drug without any information or sight (i.e., hidden administration (control group 1: HIDDEN-DRUG)). Control group 2 received a placebo infusion (saline) declared as dimetindene and also experienced the conditioning experience (PLAC+INST+COND). Itch was experimentally induced with histamine via a skin prick test. Outcome was assessed at the subjective (primary end point: experimental itch intensity, numeric rating scale), and objective level (secondary end point: wheal size, mm2 ). Experimental-induced itch intensity decreased in all groups but at different rates (P < 0.001). The groups with the open administration, whether it was dimetindene or placebo, had significantly stronger reductions in itch compared to the HIDDEN-DRUG group (OPEN-DRUG+INST+COND: P < 0.001; OPEN-DRUG+INST: P = 0.009; and PLAC+INST+COND: P < 0.001). Additional drug conditioning mediated via expectation led to a stronger reduction of itching (P = 0.001). Results on wheal size were similar (P = 0.048), however, no significant difference between the HIDDEN-DRUG group and the PLAC+INST+COND group (P = 0.967) was found. We conclude that specifically generated targeted placebo effects can significantly increase the action of a drug (dimetindene) and should be used in clinical practice.