[Seeing others is believing-analgesic placebo effects through observational learning?] / Seeing others is believing ­ Analgetische Placeboeffekte durch Beobachtungslernen?

BACKGROUND: There are many studies on placebo analgesia and its underlying mechanisms that show a significant improvement of care for chronic pain patients. However, observational learning has not been researched to this degree. OBJECTIVES: The goal of this work is to provide an overview of the research on placebo analgesia via observational learning. The evidence around whether observational learning can induce placebo analgesia will be discussed. Also, research on the factors that influence observational learning of placebo analgesia will be reviewed. MATERIALS AND METHODS: To this end, research data bases were searched for studies on placebo analgesia via observational learning. RESULTS: After inclusion and exclusion criteria were implemented, 12 studies remained. To date, there has been only one study with patients with chronic pain. The small number of included studies do not permit universal statements. However, there is preliminary evidence that observation triggers placebo analgesia as an independent mechanism. Observational learning in an experimental setting can induce placebo effects. Attention focusing on the observation might be critical. The effect sizes tend to be small to large. The effect of classical conditioning and observational learning seem to be of equal size. Live models, video recordings and even pictures of models also induce similar effects. Observational learning induces a change in expectation. DISCUSSION: The evidence included provides the theoretical basis for potential significant clinical impact. Further research is needed to extend these findings to chronic pain patients.

[Placebo effects in pain therapy]. / Placeboeffekte in der Schmerztherapie.

In the past few decades, research on pain and placebo analgesia has gained importance both scientifically and clinically. In this article, the current findings and focus of research as well as the significance of placebo research for assessing the effectiveness of pain medication are illustrated. The underlying mechanisms of placebo analgesia not only have implications for theoretical models but also offer clinically relevant guidelines for everyday interventions in pain treatment. However, many placebo phenomena are not fully understood and have to be investigated further in order to exploit the full potential of placebo effects. Interindividual differences and their inclusion in treatment will play a major role in this aspect.

[Psychological factors in the context of perioperative knee and joint pain: the role of treatment expectations in pain evolvement]. / Psychologische Faktoren im Kontext perioperativer Knie- und Gelenkschmerzen: die Rolle der Behandlungserwartungen für den Schmerzverlauf.

Chronic knee and joint pain, like all chronic pain, is a complex multidimensional event that involves somatic, psychological and social factors. Patients with knee and other joint pain experience limited mobility in their daily lives, in their professional and personal activities, and in their leisure physical exercise activities. Pain increasingly prevents them from achieving their goals. Psychological factors not only interact with neurobiological and immunological processes of pain, they play an important role in the development and maintenance of pain. Within that, expectations concerning the course of the disease and its treatment play a significant role. Study designs involving a placebo knee surgery show the high influence of these variables. The patients receiving the verum surgery do not report-as expected-less pain or better functioning than those receiving a placebo surgery. This significant influence of psychological factors may be clinically relevant. A positive patient-staff relationship-characterized by trust, warmth and empathy-is essential in order to achieve optimal therapeutic efficacy of a treatment. Every surgeon, pain physician, pain psychologist or pain physiotherapist is responsible for establishing a trusting interpersonal relationship between themselves and their patients.

Suitability of Wild Boar (Sus scrofa) as a Bioindicator for Environmental Pollution with Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS).

Wildlife species, such as roe deer, moose, brown hare, wild boar, etc., are known to accumulate persistent environmental contaminants and thus are useful as bioindicators for environmental pollution. Wild boars become exposed to perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS) from flora, fauna, water, and soil. The main exposure pathway to PFOA and PFOS is assumed to be the oral intake. From studies in domestic pigs (belonging to the same species Sus scrofa), it has been established that the oral exposure results in the liver accumulation of PFOA and PFOS. Thus, we posit that wild boars can be quantitatively used as suitable bioindicators for the presence of these substances in the environment. After the environmental pollution case in the Hessian region Sauerland in 2006, monitoring programs of individual Federal States from 2007 to 2013 showed that almost all wild boar liver samples contained PFOA and PFOS. In 2014, the analyses of PFOA and PFOS in liver of wild boars hunted in the south, north, and west of Germany showed liver concentrations at the same level among regions. Overall, an average ratio of PFOS:PFOA concentration in liver of 20.5:1 was found. To estimate the actual ratio of PFOS:PFOA in the wild boars' dietary exposure, we performed toxicokinetic modeling. According to the model, the PFOS exposure is only 2.2 times that of PFOA (because PFOS has slower elimination kinetics and higher affinity for the liver than PFOA). Overall, the determination of PFOA and PFOS in liver of wild boars indicates that both substances are ubiquitously distributed in the environment. At the same time, higher exposures were found for animals living in closer proximity to dense human populations.

The impact of neuraxial clonidine on postoperative analgesia and perioperative adverse effects in women having elective Caesarean section-a systematic review and meta-analysis.

Neuraxial clonidine improves postoperative analgesia in the general surgical population. The efficacy and safety of neuraxial clonidine as a postoperative analgesic adjunct in the Caesarean section population still remains unclear. This systematic review and meta-analysis aims to evaluate the effect of perioperative neuraxial clonidine on postoperative analgesia in women having Caesarean section under neuraxial anaesthesia. We included randomized controlled trials comparing the analgesic efficacy of the perioperative administration of neuraxial clonidine alone or in combination with a local anaesthetic and/or opioids in women having elective Caesarean section under neuraxial anaesthesia when compared with placebo. PubMed, the Cochrane Central Register of Controlled Trials, and EMBASE were searched until February 2017. Eighteen studies were included in the meta-analysis. Neuraxial clonidine reduced 24 h morphine consumption [mean difference (MD): -7.2 mg; 95% confidence interval (CI): -11.4, -3.0 mg; seven studies] and prolonged time to first analgesic request (MD: 135 min; 95% CI: 102, 168 min; 16 studies) when compared with the control group. Neuraxial clonidine increased intraoperative hypotension [odds ratio (OR): 2.849; 95% CI: 1.363, 5.957], intraoperative sedation (OR: 2.355; 95% CI: 1.016, 5.459), but reduced the need for intraoperative analgesic supplementation (OR: 0.224; 95% CI: 0.076, 0.663). The effect of clonidine on intraoperative bradycardia, intraoperative and postoperative nausea and vomiting, postoperative sedation, and pruritus were inconclusive. Neuraxial clonidine did not negatively impact neonatal umbilical artery pH or Apgar scores. This review demonstrates that neuraxial clonidine enhances postoperative analgesia in women having Caesarean section with neuraxial anaesthesia, but this has to be balanced against increased maternal adverse effects.

[Psychological treatments for pain in cancer patients : A systematic review on the current state of research]. / Schmerzpsychologische Interventionen bei onkologischen Patienten : Ein systematisches Review zum aktuellen Stand der Forschung.

BACKGROUND: In cancer patients, pain is one of the main symptoms and especially in the late stages of disease, these symptoms can be associated with considerable suffering. In psycho-oncology, preliminary psychological therapies targeting cancer pain have been tested; however, a systematic review of available interventions is lacking, especially considering their dissemination, evidence base, study quality, and the comparison with established treatments. Therefore, the aim of the current study is to systematically review the current research on psychological treatments for pain in cancer patients. MATERIALS AND METHODS: During May 2014, MEDLINE, PsycINFO, PSYNDEX, and CENTRAL databases were searched. Psychological treatments for pain in adult cancer patients studied in randomized, controlled trials (RCTs) and referring to pain as primary or secondary outcome were included. After examination for inclusion, structured data extraction and assessment followed. Data were synthesized narratively. RESULTS: In the review, 32 RCTs were included. Studies mainly referred to patients with breast cancer or patients in earlier stages of the disease. The methodological quality of included studies was heterogeneous. Most commonly, short interventions were delivered by nurses in out-patient settings. Interventions including education and relaxation techniques were utilized most often, followed by interventions with behavioral or cognitive components. CONCLUSION: A need for research persists regarding efficacy of current psychotherapeutic interventions, or the role of mediator variables (e. g., coping) on pain perception in cancer patients. Studies with high methodological quality which comprehensively and transparently report on interventions and designs are lacking.

[Placebo response - Mechanisms and clinical applications]. / Placeboreaktion ­ Mechanismen und klinische Anwendungen.

Research on placebo responses has made major progress in recent years. Placebo responses are psychobiological events, which are created by the entire therapeutic context. They can appear at any time, not only in experimental and clinical settings. Several studies on analgesia-related placebo research showed that patients have higher placebo responses in comparison to healthy participants, which may also last longer. Expectations play a key role in placebo analgesia. They can be induced via three central psychological mechanisms: 1) expectation induced via instructions, 2) expectation induced via classical conditioning and 3) expectation induced via social learning. These mechanisms are controlled by neurobiological structures and modulate pain perception resulting in pain relief by positive expectations and increased pain by negative expectations, the so-called nocebo effect. There is an ongoing discussion that these psychological mechanisms may also play a central role in inducing and maintaining itch-reducing placebo responses. The current state of research suggests that placebo responses could be used in clinical contexts and should not be viewed as being in competition with medications but as an additive increase in efficacy of a pharmacological substance through specifically induced placebo responses. This targeted use is also possible within ethical guidelines. Important prerequisites are that the research results can be transferred from healthy participants to patients and that the placebo responses are reproducible.

Treatment history and placebo responses to experimental and clinical pain in chronic pain patients.

BACKGROUND: Placebo analgesia refers to the reduction in pain due to the administration of an inert treatment. It is induced by expectations of pain relief which are enhanced by learning mechanisms. In healthy humans, prior positive experiences enhance the placebo response. However, the effects of patients' prior experiences with treatment on placebo responses have not yet been examined. This study investigated how verbal information, learning and treatment history influence the magnitude of placebo analgesia in chronic pain. METHODS: We administered a pharmacological placebo intervention in a sample of chronic pain patients (n = 49) who were seeking treatment in an outpatient pain clinic. Analyses were based on placebo responders. RESULTS: We found that verbal information about a potent pain-relieving effect of the intervention induced a large placebo analgesic response to both acute experimental (F(1,44) = 43.35, p < 0.001) and chronic pain (F(1,44) = 37.72, p < 0.001). However, the placebo responses to experimental and chronic pain were not significantly related (r = 0.012, p = 0.95). An additional conditioning procedure did not significantly enhance placebo analgesia. Treatment history modulated the magnitude of the placebo response: patients with a more negative pain-related treatment history reported significantly larger placebo responses to their own chronic pain (τ = 0.271, p = 0.044). CONCLUSIONS: We could show that placebo responses to both acute and chronic pain are high in pain treatment settings and that treatment history modulates this effect. Different mechanisms might underlie placebo responses to acute and chronic pain. Our findings highlight the necessity of considering placebo responses and treatment history in the treatment of chronic pain. WHAT DOES THIS STUDY ADD?: Placebo analgesia following verbal information of potent pain relief is high in chronic pain patients in a clinical setting. It is modulated by treatment history. Different mechanisms might underlie placebo analgesia to acute and chronic pain.

[Effects of interdisciplinary functional restoration treatment with cognitive behavior therapy in patients with chronic back pain: healthcare research in the context of selective contracts]. / Effekte eines interdisziplinären Functional-restoration-Behandlungsprogramms mit kognitiv-behavioraler Therapie beim chronischen Rückenschmerz : Versorgungsforschung im Kontext von Selektivverträgen.

INTRODUCTION: The efficacy of functional restoration programs for the treatment of chronic back pain is well documented. Nevertheless, there are only a few such centres in Germany and few trials have been conducted in German-speaking regions to demonstrate that implementing such programs in everyday clinical settings with large numbers of patients is just as effective as in a research setting. The present study examined whether the positive effects of such programs can also be observed in the clinically relevant context of a standardized day clinic treatment regimen. MATERIAL AND METHODS: A total of 681 back pain patients in 2 German cities were examined at 4 measurement points (before and immediately after the program, as well as 6 and 12 months after treatment) using a comprehensive questionnaire on perceived pain and symptoms of anxiety and depression, as well as the work situation. RESULTS: In both cities significant and long-term improvements in back pain, pain-related impairment and degree of chronification were observed, as well as a high return-to-work rate after treatment. Hence, the quality of such programs was also confirmed for a large patient population.

Prevention of intradialytic hypotension in patients with acute kidney injury submitted to sustained low-efficiency dialysis.

OBJECTIVES: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). METHODS: Patients were randomly assigned to two SLED prescriptions-control group, dialysate temperature was 37.0°C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5°C with a variable sodium concentration [150-138 mEq/L] and UF rate. RESULTS: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 ± 1.25 L vs. 1.59 ± 1.03 L in control, p = 0.04) when compared with control group. CONCLUSIONS: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

[Comparative psychological aspects of itching and pain]. / Vergleichende psychologische Aspekte von Juckreiz und Schmerz.

Itching is a major symptom of chronic skin diseases such as atopic dermatitis and leads to considerable psychological strain. Chronic itching lowers patient's quality of life similar to chronic pain and influences the medical treatment. The frequently resulting scratching behavior (short-term avoidance of itch) leads to continuation and exacerbation of the disease, just as with specific pain behavior. For the development of itching and pain psychosocial factors have been identified in addition to somatic ones. However, recent data suggest that there is a complex interaction between pain and itching and comparable mechanisms of neuronal sensitization. In contrast to traditional biomedical one-dimensional models which focus mainly on physical and not psychological factors of a disease, recent data support a biopsychosocial model of development and maintenance for itching and pain. Biopsychosocial understanding of a disease should consequently be taken as the basis for treatment and the importance of interdisciplinary treatment is emphasized. This article will focus on chronic itching and pain with particular consideration of psychological factors.

[Measures of success in treatment of chronic back pain: pain intensity, disability and functional capacity: determinants of treatment success in multimodal day clinic setting]. / Vorhersage verschiedener Erfolgsmaße in der Behandlung chronischer Rückenschmerzen: Schmerzintensität, Beeinträchtigung und Funktionskapazität: Determinanten des Behandlungserfolges in einem tagesklinischen multimodalen Setting.

INTRODUCTION: The empirical findings on risk factors for a favorable/unfavorable outcome upraised via pain intensity, disability and functional capacity after empirically well-evaluated multimodal treatment are inconsistent. The objective of this study was to analyze the relevance of psychosocial and pain-related variables for therapeutic outcome in an unselected sample of patients with chronic non-specific back pain (CBP). METHODS: Included were 681 patients with CBP referred to an outpatient-based multidisciplinary pain rehabilitation program and 320 took part in a survey 12 months later. Before, directly after and 12 months after the program the patients received a questionnaire which contained pain-related items on pain intensity, disability, self-reported functional capacity which were defined as outcome variables, psychological items (anxiety, depression) and work-related items which represented probable predictor variables. Multivariable regression analyses were calculated to estimate the contribution of the selected parameters on pain intensity, disability and functional capacity. RESULTS: The calculated regressions showed only a moderate ability to predict or explain the outcomes pain intensity, disability and functional capacity. However, depression and body mass index (BMI) were significantly related to pain-related therapeutic outcome.

Cellular senescence induced by aberrant MAD2 levels impacts on paclitaxel responsiveness in vitro.

BACKGROUND: The mitotic arrest deficiency protein 2 (MAD2) is a key component of the mitotic spindle assembly checkpoint, monitoring accurate chromosomal alignment at the metaphase plate before mitosis. MAD2 also has a function in cellular senescence and in a cell's response to microtubule inhibitory (MI) chemotherapy exemplified by paclitaxel. METHODS: Using an siRNA approach, the impact of MAD2 down-regulation on cellular senescence and paclitaxel responsiveness was investigated. The endpoints of senescence, cell viability, migration, cytokine expression, cell cycle analysis and anaphase bridge scoring were carried out using standard approaches. RESULTS: We show that MAD2 down-regulation induces premature senescence in the MCF7 breast epithelial cancer cell line. These MAD2-depleted (MAD2) cells are also significantly replicative incompetent but retain viability. Moreover, they show significantly higher levels of anaphase bridges and polyploidy compared to controls. In addition, these cells secrete higher levels of IL-6 and IL-8 representing key components of the senescence-associated secretory phenotype (SASP) with the ability to impact on neighbouring cells. In support of this, MAD2 cells show enhanced migratory ability. At 72 h after paclitaxel, MAD2 cells show a significant further induction of senescence compared with paclitaxel naive controls. In addition, there are significantly more viable cells in the MAD2 MCF7 cell line after paclitaxel reflecting the observed increase in senescence. CONCLUSION: Considering that paclitaxel targets actively dividing cells, these senescent cells will evade cytotoxic kill. In conclusion, compromised MAD2 levels induce a population of senescent cells resistant to paclitaxel.

[Patients with pre-existing chronic pain and/or psychological problems]. / Patienten mit vorbestehender Schmerzchronifizierung und/oder psychischen Auffälligkeiten.

Existing pain chronification and psychological problems can affect the degree of perioperative pain and hence the postoperative outcome. Most elective surgery performed on the musculoskeletal system is indicated because of pain. To avoid perioperative complications it is therefore essential to identify patients with existing pain chronification before surgery is performed. Based on a systematic literature review, studies on orthopaedic surgery were filtered for existing pain chronification and checked in order to deduce clinically relevant and evidence-based recommendations. In summary, unproblematic pain is characterised by good organic explainability, lack of pain generalisation, no additional physical complaints, appropriate management of the physical damage encountered and suitable use of analgesics. In line with what is known about the mechanisms of pain chronification, patients with existing chronification usually display additional psychological problems. These psychological factors ought to be established prior to surgery. A preliminary non-surgical treatment could potentially also lead to a reassessment of the indication for surgery.

[Can failed back surgery be prevented? Psychological risk factors for postoperative pain after back surgery]. / Lässt sich eine "failed back surgery" verhindern? Psychologische Risikofaktoren für postoperative Schmerzen nach Wirbelsäulenoperationen.

Aside from the surgical technique used, the development of peri- and postoperative pain and impairments in patients following intervertebral disk surgery is also determined to a crucial extent by psychological factors. Based on a systematic literature review, we checked whether evidence-based recommendations could be deduced on how to take into account psychological risk factors in back surgery in order to avoid postoperative complications, such as failed back surgery syndrome. The current state of research suggests three groups of risk factors: (1) negative psychological factors, (2) preexisting pain chronification, and (3) psychological disorders. In the case of elective intervertebral disk surgery, these factors should therefore be determined and identified preoperatively and taken into account in the indication for surgery. Multimodal treatments could conceivably prove to be more effective, or else psychological pain management therapy might be considered prior to surgery so as to avoid postoperative complications. If surgery is medically unavoidable despite existing risk factors, postoperative treatment should incorporate psychological pain management therapy at an early stage in the context of a multidisciplinary approach.

Complicaciones postoperatorias de la serie prospectiva de pacientes con hernioplastia inguinal, en protocolo de hospitalización acortada del Hospital Dr. Gustavo Fricke de Viña del Mar / Complications of inguinal hernia repair

La hernioplastia es la técnica quirúrgica más comúnmente realizada por el cirujano general. Desde la década de los 80, existe un auge por la cirugía ambulatoria en esta patología. Objetivo: Evaluar la incidencia de complicaciones postoperatorias y posibles asociaciones con factores de riesgo, en hernioplastia inguinal electiva en protocolo de hospitalización abreviada. Material y Método: Serie de casos prospectiva de 214 pacientes operados de hernia inguinal, entre abril del 2003 y noviembre del 2005. Se excluyeron los pacientes con ASA III y IV. El análisis estadístico fue realizado mediante la prueba de Chi cuadrado (univariables), y regresión logística (multivariables), SPSS 11.0. p <0,05. Resultados: El promedio de edad fue de 54,3 años (17-84), predominio masculino (90,7 por ciento). Se controló al 100 por ciento de los casos en los primeros 30 días de la intervención, control telefónico (78 por ciento), y en el policlínico (100 por ciento). Complicaciones postoperatorias presentaron el 14,9 por ciento de los casos, la más frecuente fue el seroma (4,2 por ciento), la más grave atrofia testicular y dolor crónico invalidante en 1 paciente (0,47 por ciento), debiendo finalmente realizar orquiectomía. Infección de herida operatoria correspondió al 0,47 por ciento, un paciente ASA I. Los menores de 65 años tuvieron un riesgo relativo de 2,31 de presentar complicaciones. El nivel de satisfacción usuaria fue bueno. El 90 por ciento ha sido controlado hasta agosto del 2006, media de seguimiento de 24 meses y sin presentar recidiva. Conclusiones: La herniorrafia inguinal con hospitalización abreviada, en el hospital Dr. Gustavo Fricke de Viña del Mar, tiene significativamente mayores complicaciones en los menores de 65 años. También ha logrado niveles de satisfacción adecuados, con un mínimo de complicaciones postoperatorias inmediatas.

Background: Hernia repair in adults is the most commonly performed surgical procedure by general surgeons. Aim: To evaluate the incidence of postoperative complications in elective inguinal hernioplasty with abbreviated hospital stay. Material and Methods: Prospective series of 214 patients aged 16 to 84 years (194 males), operated for inguinal hernia between April 2003 and November 2005. Patients classified as American Society of Anesthesiologists (ASA) III or IV were excluded from the study. Results: All patients were followed during the first 30 days after surgery by telephone and control at the outpatient clinic. Fifteen percent had complications. The most common was seroma in 4 percent and the most serious was a testicular atrophy and chronic invalidating pain in one patient, that required an orchidectomy. One patient had a surgical wound infection. Patients of less than 65 years had an odds ratio of 2.13 for complications, when compared with their older counterparts. The level of client satisfaction was good. After 24 months of follow up 90 percent of patients were under control and without relapse. Conclusions: Inguinal hernia repair with abbreviated hospital stay has a low incidence of complications.