Efficacy of open-label counterconditioning for reducing nocebo effects on pressure pain

Nocebo effects can adversely affect the experience of physical symptoms, such as pain and itch. Nocebo effects on itch and pain have shown to be induced by conditioning with thermal heat stimuli and reduced by counterconditioning. However, open-label counterconditioning, in which participants are informed about the placebo content of the treatment, has not been investigated, while this can be highly relevant for clinical practice. Furthermore, (open-label) conditioning and counterconditioning has not been investigated for pain modalities relevant to musculoskeletal disorders, such as pressure pain. In a randomized controlled trial, we investigated in 110 healthy female participants whether nocebo effects on pressure pain combined with open-label verbal suggestions can be 1) induced via conditioning and 2) reduced via counterconditioning. Participants were allocated to either a nocebo or sham conditioning group. Next, the nocebo group was allocated to either counterconditioning, extinction, or continued nocebo conditioning; sham conditioning was followed by placebo conditioning. Nocebo effects were significantly larger after nocebo conditioning than sham conditioning (d = 1.27). Subsequently, a larger reduction of the nocebo effect was found after counterconditioning than after extinction (d = .99) and continued nocebo conditioning (d = 1.63), with effects similar to placebo conditioning (following sham conditioning). These results show that (counter)conditioning combined with open-label suggestions can modulate nocebo effects on pressure pain, which provides promise in designing learning-based treatments to reduce nocebo effects in patients with chronic pain disorders, particularly for musculoskeletal disorders.

Cold Conditioning of Adolescents Aged 15–16 Years in an Educational Institution

This paper analysed the results of morning preventive activities based on exposure to contrasting temperatures in combination with physical exercises in an educational institution. The study involved 18 adolescent boys aged 15–16 years. Preventive activities were performed three times a week and included certain stages. Selection criteria were developed for the conditioning group and admission to the conditioning activities. Anthropometric and physiometric indicators as well as the number of common cold cases during the year were analysed. We found that preventive measures including exposure to contrasting temperatures produced no effect on the natural physiological processes in this age group. At the same time, the common cold incidence rate decreased by 30 % in the conditioning group.

To Experience or to Be Informed? Classical Conditioning Induces Nocebo Hyperalgesia even when Placebo Analgesia Is Verbally Suggested—Results of a Preliminary Study

Objective To investigate whether direct experience (i.e., classical conditioning) or verbal suggestion is more important in inducing nocebo hyperalgesia, five groups (total sample size, N = 99) were studied: conditioning, congruent conditioning, incongruent conditioning, verbal suggestion, and control. Methods Participants in groups with conditioning experienced more intensive pain stimuli after presentation of a white circle. In the congruent conditioning group, suggestion that the circle would precede more intensive pain stimuli was additionally provided, whereas in the incongruent conditioning group, the opposite suggestion was used. Control and verbal suggestion groups received pain stimuli of one intensity; however, the latter received suggestion that a circle would precede pain stimuli of higher intensity. Results The nocebo effect was observed in all conditioning groups, regardless of the verbal suggestions used. Moreover, the experience of hyperalgesia was able to nullify the effect of the verbal suggestion of analgesia. Incongruence between verbal suggestion and pain experience produced expectancies that affected nocebo hyperalgesia. Conclusions The results of this preliminary study suggest that direct experience seems to be more important than verbal suggestion in inducing nocebo hyperalgesia.

Tone it Down: How Fitness Instructors’ Motivational Comments Shape Women’s Body Satisfaction

Two-hundred and three college women participated in a 16-minute strength and conditioning group fitness class. Participants were randomly assigned to a class that featured either appearance-focused motivational comments by the instructor (e.g., “Blast that cellulite!”) or function-focused comments (e.g., “Think of how strong you are getting!”). Body satisfaction from pre-test to post-test increased overall, but those in the function-focused (as opposed to appearance-focused) condition experienced a significantly greater increase in body satisfaction. A similar pattern was observed for positive affect. Additionally, those in the function-focused condition described the class in more positive terms and reported experiencing less body surveillance during the class. These findings are consistent with research suggesting that exercise can improve mood and body satisfaction, but also suggest that a more function-focused class can lead to even greater improvements. The motivational comments fitness instructors use may have a notable impact on women’s mood, body satisfaction, and body surveillance.

Effects of Sufentanil Postconditioning on Myocardial Ischemia-Reperfusion Injury in Rats In Vivo

Objective.To investigates the effects of sufentanil post conditioning on Myocardial ischemia reperfusion injury in rats in vivo.Methods.To randomly divide 40 male SD rats equally into 4 groups, including Sham group, ischemia-reperfusion group (Group I/R ), ischemic post conditioning group (Group IPO) and sufentanil post conditioning group (Group SUF). The left anterior descending coronary arterys (LAD) of rats in 4 groups are ligated for 30 minutes and are re-perfused for 120 mins. To measure the myocardial infarction size (IS/AAR%) with double-staining with Even's blue and triphenyltetrazolium chloride, to calculate the concentration of cTnI, and to observe the HE staining and the expression of Bcl-2 and Bax.Result. Comparing with Group 1/R, the myocardial infarction size (IS/AAR%), and the concentration of cTnI in Group IPO and SUF all reduced significantly. Comparing with Group 1/R, cell morphological observation shows less change in pathology. And the expression of Bcl-2 increases and expression of Bax decreases in Group IPO and SUF than that in Group 1/R.Conclusion. Sufentanil post conditioning has protective effects on myocardial ischemia-reperfusion injury in rats in vivo.

A comparison of cardiac post-conditioning and remote pre-conditioning in paediatric cardiac surgery

BackgroundRemote ischaemic pre-conditioning and cardiac ischaemic post-conditioning provide myocardial protection in cardiac surgery. However, these two endogenous strategies have not been directly compared in a clinical setting. The purpose of this study was to compare the efficacy of remote ischaemic pre-conditioning and post-conditioning in providing myocardial protection to children undergoing cardiopulmonary bypass for surgical repair of ventricular septal defect.MethodsWe randomly assigned 60 paediatric patients scheduled for surgical correction of congenital ventricular septal defect to the post-conditioning group (n = 20), remote pre-conditioning group (n = 20), or control group (n = 20). Post-conditioning consisted of 30 seconds of ischaemia and 30 seconds of reperfusion achieved by clamping and unclamping the aorta, repeated three times over 3 minutes immediately after cardioplegic arrest. Remote ischaemic pre-conditioning consisted of 5 minutes of lower limb ischaemia followed by 5 minutes of reperfusion using a blood-pressure cuff inflated to a pressure of 200 millimetres of mercury, also repeated three times over 30 minutes. We assayed creatine kinase-MB, troponin I.ResultsMean age, cardiopulmonary bypass times, and aortic cross-clamp times were matched across groups. Both post-conditioning and remote ischaemic pre-conditioning reduced the peak release of creatine kinase-MB (86.1 plus or minus 24.1 units per litre and 92.8 plus or minus 20.6 units per litre, respectively, versus 111.0 plus or minus 44.6 units per litre in the control, p less than 0.05) and troponin I (0.28 plus or minus 0.10 nanogram per millilitre and 0.26 plus or minus 0.09 nanogram per millilitre, respectively, versus 0.49 plus or minus 0.19 nanogram per millilitre in the control group, p less than 0.05).ConclusionsOur study demonstrates that ischaemic post-conditioning and remote ischaemic pre-conditioning provide comparable myocardial benefit in children undergoing cold blood cardioplegic arrest.

Comparison of Outcomes for Non-Myeloablative (NMA) and Myeloablative (MA) Conditioning for Adults with Acute Lymphoblastic Leukaemia (ALL) in First and Second Complete Remission (CR): a Center for International Blood and Marrow Transplant Research (CIBMTR) Analyisis.

Abstract 872 The efficacy of reduced intensity or NMA conditioning for allogeneic hematopoietic stem cell transplantation (HCT) for adults with ALL is uncertain. Using CIBMTR data we compared the outcomes of 92 patients ≥16 years who had NMA conditioning with 1421 patients who had myeloablative conditioning (MC) for allografts using sibling and unrelated donors for ALL in CR1 or CR2. Conditioning in the NMA group included regimens containing busulfan ≤ 9 mg/kg (27), melphalan ≤ 150 mg/m2 (23) or low-dose total body irradiation (36) and others (7). The NMA conditioning group were older (median 45 vs. 28 years, p<0.001) and more received peripheral blood grafts (73% vs. 43%, p<0.001). Other major potential prognostic factors were similar in the two groups. After a median follow-up of 54 vs. 38 months respectively, the NMA vs. MA conditioning groups had slightly less acute grade 2-4 graft-vs-host-disease (GVHD), less chronic GVHD but similar transplant-related mortality (TRM). However the NMA conditioning group experienced slightly more relapse (35% vs. 26%, p=0.08) yet similar overall survival (OS) (Figure): Outcome:MANMAP-value Acute GVHD @ 100 days, grades (2-4)46 (43-49)39 (29-49)0.16 Chronic GVHD @ 3 years42 (39-44)34 (24-44)0.16 TRM @ 3 years, %33 (31-36)32 (23-43)0.86 Relapse @ 3 years, %26 (23-38)35 (25-46)0.08 Leukemia-free survival (LFS) @ 3 years, %41 (38-44)32 (22-43)0.12 OS @ 3 years, %43 (40-46)38 (28-49)0.39 Multivariate analysis showed that a low Karnofsky score (KPS) and T cell depletion were associated with higher TRM but conditioning intensity had no impact on TRM (RR with NMA 0.97, P=0.89). Relapse risk with NMA conditioning was slightly, but not significantly higher ( (RR)=1.34, p=0.15) as was a CR2, particularly with a short (<12 months) initial CR (RR=2.74; longer remission (12 months) RR1.51, P<0.0001). Multivariate analysis demonstrated significantly improved OS with: KPS>80, CR1, lower WBC, no extramedullary disease, a well matched unrelated or a sibling donor, transplant since 2001, in younger patients (<30y), conditioning without TBI and GVHD prophylaxis without T-cell depletion. However ATG use did not affect survival.. The most common cause of death was relapse; which was similar in MA and NMA HCT (46% vs. 35%). Despite the older age in the NMA group, OS and LFS at 3 years was similar to those receiving MA HCT. In comparing the outcomes of NMA and MA conditioning in sibling vs. unrelated donor transplant recipients we found that there was slightly, but not significantly more relapse with NMA [34 (18-52)% vs. 26 (23-30)%, p=NS and 36 (24-49)% vs. 25 (22-28)%, p=NS respectively]. This was associated with similar OS of 40 (23-59)% vs. 50 (45-54)% and 37 (25-50) vs. 38 (34-41)% in the sibling and unrelated donor groups. Conclusions: These data suggest that NMA conditioning is worthy of investigation in prospective clinical trials of adult ALL. These trials should include both well matched unrelated and related donors, but importantly, NMA conditioning may not fully overcome the adverse impact of poor pre-HCT KPS on outcome. >Disclosures: No relevant conflicts of interest to declare.

Standard and Reduced Intensity Allogeneic Hematopoietic Stem Cell Transplantations (HSCT) from Related and Unrelated Donors for Chronic Lymphocytic Leukemia (CLL). a Long-Term Follow-up (10 years) Study from the EBMT Registry. (CLL Sub-Committee on Behalf of EBMT CLWP)

This retrospective analysis concerned 374 patients (pts) who underwent an allogeneic HSCT for CLL reported to the EBMT registry. There were 282 males (75%) and 92 females with a median age of 53 years (24–69). The interval between diagnosis and transplantation was 53 months (3–308). Forty-five pts (12%) have received a previous HSCT. At transplant, 302 among 323 evaluated patients had a good performance status (PS) (93%), 51 pts were in CR (14%), 163 in PR (45.5%), 39 in SD (11.5%) and 105 in PD (29%) among 353 evaluated patients. Two hundred and ninety-two pts received a standard (Std) and 82 a reduced intensity conditioning regimen (RIC); 314 pts received PBSC, 55 BM and 5 cord blood cells from 202 HLA siblings (Sib), 2 mismatched related donors and 170 unrelated donors (UD). There were 136 (36%) sex-mismatched (90 F/M and 46 M/F), 150 pairs (40%) had an ABO incompatibility (61 minor, 99 major) and for CMV: 80 pairs were +, 148− and 112 mixed. After transplantation, 359 pts engrafted, 201 pts developed an AGVHD (gr I: 76, gr II : 79, gr III: 30 and gr IV:16) and 153 presented a cGVHD (75 limited and 78 extensive). At day 100 after transplant, the cumulative incidence of AGVHD for the total population was 17% (13–22) for gr I, 31% (26–36) for gr ≥ II. [Sib: 19% (13–25) gr I and 27% (21–34) gr ≥ II; UD: 16% (9–22) gr I and 38% (29–47) gr ≥ II]. Results concerning the cumulative incidence of AGVHD according to HLA typing and kind of conditioning are shown in Table I. At 1 year after transplant for the total population, the cumulative incidence of limited and extensive cGVHD were 15 % (6–24) and 29.5% (18–41) for Std; 18.6 (13–24) and 18% (13–23) for RIC respectively. With a median follow up of 38 months, the probability of 3-year and 5-year overall survival (OS) and disease-free survival (DFS) for the total group were 56% (51–62) and 47.4 % (42–53); 49 % (43–56) and 42% (36–48.5) respectively. We observed a significant difference concerning 5-year OS according to the pretransplant disease status [CR: 73% (60–89), PR: 57% (48–68) and PD: 35% (26–46)] (p&lt;0.00001). There was no significant difference between standard and RIC HSCT in term of OS with 52.4 % (42–66) and 47% (40–55.5) respectively (p=0.44) (Figure 1) [Std and RIC Sib: 51% (37–70) and 56% (47–67); Std and RIC UD: 60% (44–83) and 40% (29–55) respectively]. The multivariate analysis using Cox model showed a significant impact of 3 factors on OS: age: HR=1.061 (1.02–1.10) p&lt;0.0001, gender: HR=2.29 (1.02–5.11) p=0.04 and PS: HR=3.15 (1.40–7.10) p=0.005. The cumulative incidence of non-relapse and relapse mortality (NRM and RM) at 3 months and 1 year after transplant were: 10 % (7–13), 5% (3–7) and 24% (19–28), 15% (12–19) respectively [Std:23 % (11–35.6), 6% (0–14) 1 year; RIC: 22.5% (17.5–27), 18% (13–22) at 1 year]. Results concerning the cumulative incidence of NRM and RM according to HLA typing and kind of conditioning are shown in Table I. This large retrospective analysis showed a high percentage of long-term OS after HSCT for CLL either after Std or RIC conditioning without any difference between the 2 groups except for the AGVHD (gr I, III and IV) where we had an higher incidence in the Std group, and for the RM with a higher level in the RIC group. Moreover, we demonstrated the important impact of disease status pretransplant (univariate); age, PS and sex-matching (multivariate) on the global OS. Table 1: cumulative incidence of AGVHD, NRM and RM according to HLA typing and kind of conditioning Figure Figure 1. Probability of OS for Standard conditioning group and RIC group Figure 1. Probability of OS for Standard conditioning group and RIC group