Understand placebo effect to better treat pain

PURPOSE: The clinical efficiency of every therapeutic, medicinal or other, contains a part of not specific effect, or placebo effect, of which the frequency of appearance and the importance, in the treatment of pain, can be particularly raised. The practitioners use often, deliberately either not, this effect to modulate their therapeutic efficiency, or in a diagnostic purpose to investigate the mechanism of a pain; our objective is to analyze, in the light of a review of the recent medical literature, what the understanding of the placebo effect brings to the treatment of pain. CURRENT KNOWLEDGE AND KEY POINTS: Neurobiologic mechanisms which sub-aim placebo effect begin to be understood by several studies showing the role of endogen opioid mechanisms. Other studies allow better to understand the psychological determiners of the effect placebo: conditioning mechanisms, and/or cognitive variables, as expectations of the patient or the therapist. FUTURE PROSPECTS AND PROJECTS: At term of this review, we will conclude that the use of a placebo has no value of diagnostic test as for the mechanism of the pain; it is neither necessary nor desirable to implement placebo effect in the daily practice because any therapeutics acts by associating specific and not specific effects. The quality of the relation doctor-patient will allow to mobilize not specific factors susceptible to modulate favorably any therapeutic action. For controlled clinical trials, certain methodologies can be envisaged to by-pass the administration of placebo, reducing so ethical constraints bound to their use.     

Social learning contributions to the etiology and treatment of functional abdominal pain and inflammatory bowel disease in children and adults

This paper reviews empirical work on cognitive and social learning contributions to the etiology and treatment of illness behavior associated with functional abdominal pain and inflammatory bowel disease. A particular emphasis is placed on randomized controlled trials, the majority of which are multi-modal in orientation, incorporating elements of cognitive behavioral therapy, social learning, and relaxation. Based on this review, we offer methodological and clinical suggestions: (1) Research investigations should include adequate sample sizes, long-term follow-up assessments, and a credible, active control group. (2) Standard gastrointestinal practice should include, when appropriate, learning opportunities for patients and family members, for example, instruction regarding the encouragement of wellness behavior.     

Acupuncture Analgesia:1. Review of Clinical Studies

Recent clinical studies, both uncontrolled and controlled, of the use of acupuncture for the relief of chronic pain are reviewed. The success rate demonstrated by controlled trials is markedly lower than that claimed in reports of the clinical use of acupuncture in which no attempt is made to control factors which influence the placebo response. A/though on balance of evidence it appears that acupuncture has a place in the management of chronic pain resistant to orthodox therapeutic measures, more research is needed both to establish objective criteria for the assessment of the effect, or lack of effect, of acupuncture on chronic pain as well as to delineate clearly the patient groups and the conditions where acupuncture analgesia is indicated.     

Arterial thromboembolism in the pediatric population

The most common cause of arterial thromboembolism in the pediatric population is secondary to arterial catheterization. Non-catheter-related arterial thromboembolism is rare. The frequency of this complication has paralleled the advances in pediatric tertiary care that has lead to increasing numbers of children surviving life-threatening primary illnesses. Previously, these events were very rare and children were managed according to adult protocols. It is now known that the pathophysiology of thrombosis in children differs from that of adults and indeed is different for that of various age groups within the pediatric population, therefore requiring a unique diagnostic and therapeutic approach. This review highlights the available published data to support an evidence-based approach to the complication of arterial thromboembolism in the pediatric population, and underscores the urgent need for further randomized controlled trials.     

Lack of clarity in the definition of treatment-related mortality: pediatric acute leukemia and adult acute promyelocytic leukemia as examples

Treatment-related mortality (TRM) is important in acute lymphoblastic leukemia and acute myeloid leukemia (AML); however, little is known about how TRM is defined across trials. Two major problems are related to what constitutes treatment versus disease-related cause of death and to TRM attribution (for example, death because of infection or hemorrhage). To address the former, we conducted a systematic review of randomized therapeutic pediatric acute leukemia and adult/pediatric acute promyelocytic leukemia trials and any study type focused on TRM in pediatric acute leukemia. We described definitions used for TRM. Sixty-six studies were included. Few therapeutic pediatric acute lymphoblastic leukemia studies (2/32, 6.3%) provided definitions for TRM, whereas more therapeutic pediatric AML studies (6/9, 66.7%) provided definitions. There was great heterogeneity in TRM classification. The authors of most studies relied on deaths during induction or in remission to delineate whether a death was TRM. However, 44.4% of therapeutic AML studies used death within a specific time frame to delineate TRM. We suggest that a consistent approach to defining and determining attribution for TRM in acute leukemia is an important future goal. Harmonization of definitions across the age spectrum would allow comparisons between pediatric and adult studies.     

Gene therapy for ischemic cardiovascular diseases: some lessons learned from the first clinical trials

Stimulation of angiogenesis, arteriogenesis, and lymphangiogenesis (i.e., therapeutic vascular growth) is a new concept for the treatment of ischemic cardiovascular diseases. A wealth of information is already available about the mechanisms and mediators of angiogenesis and arteriogenesis, which has led to the first randomized, controlled, phase II/III trials with recombinant growth factors or their genes. Even though end points predefined in the study protocols have been positive in several trials, it is still evident that the trials have not produced any clearly meaningful clinical benefits for the patients. This review addresses same questions and concepts related to the gene therapy-based applications of therapeutic vascular growth.     

Juvenile spondyloarthropathy

The juvenile-onset spondyloarthropathies are a group of pediatric disorders characterized by arthropathy and enthesopathy and a variety of extra-articular symptoms. With the application of new classification criteria, there is an increasing recognition of these diseases. This review summarizes recent advances in etiologic factors, clinical manifestations, therapeutics, and prognosis. Improved recognition of juvenile-onset spondyloarthropathies has allowed systematic and rigorous treatment trials to evaluate clinical outcomes relevant to pediatric medicine. Thus far, current therapeutic options allow for symptomatic control only. Further treatment studies are needed to examine the possibility of disease modification of juvenile-onset spondyloarthropathies.     

Need for a comprehensive medical approach to the neuro-immuno-gastroenterology of irritable bowel syndrome

Irritable bowel syndrome (IBS) is defined by the Rome Ⅲ criteria as symptoms of recurrent abdominal pain or discomfort with the onset of a marked change in bowel habits with no evidence of an inflammatory,anatomic,metabolic,or neoplastic process.As such,many clinicians regard IBS as a central nervous system problem of altered pain perception.Here,we review the recent literature and discuss the evidence that supports an organic based model,which views IBS as a complex,heterogeneous,inter-dependent,and multi-...     

Antacid and placebo produced similar pain relief in duodenal ulcer patients.

The effectiveness of antacid and placebo in relieving single episodes of spontaneous duodenal ulcer pain were compared in two double blind, controlled, randomized trials. The trials compared the effects on ulcer pain of individual doses of a liquid antacid and placebo, rather than the effects of therapeutic regimens with antacid or placebo. Thirty patients were studied. There were no significant differences between antacid and placebo in time to onset, degree, or duration of pain relief. These results suggest that factors other than gastric acid neutralization are important in acute relief of spontaneous duodenal ulcer pain.     

Chronic constipation and abdominal pain: Independent or closely interrelated symptoms?

Constipation is both a symptom and a disorder, seen in both functional constipation and irritable bowel syndrome with constipation predominance (IBS-C). Despite the Rome IV criteria distinguishing between these conditions, they share many therapeutic approaches. This review aims to explore the relationship between constipation and abdominal pain and assess the evidence surrounding whether laxation improves abdominal pain and whether such a response to laxation differs between IBS-C and functional constipation. In patients with functional constipation, increasing frequency of bowel motions by laxatives regardless of mechanism of action is associated with reductions in the severity of abdominal pain, supporting the role of constipation as a contributor to abdominal discomfort. In patients with IBS-C, evidence from systematic reviews indicates that abdominal pain is driven by factors additional to constipation alone and that visceral analgesic modulation is also needed to optimize pain. Changing definitions of IBS-C and heterogeneity in clinical trial design including endpoints have raised uncertainty about the comparative ability of older laxatives without known neuromodulatory effects to improve chronic abdominal pain compared with new secretagogues and prokinetics for the management of IBS-C. While it is known that abdominal pain is associated with constipation and laxation contributes to relief of that pain, it remains unproven whether proposed visceral analgesic properties of new laxatives provide greater pain relief than laxation alone. However, it is likely that the response to laxation in IBS-C is only part of the puzzle.     

Schmerzsyndrome des Bewegungsapparates bei Kindern und Jugendlichen

Chronic pain syndromes in children and adolescents are defined as continuous or recurrent pain without an underlying causative diagnosis and lasting for more than 3 months. It is estimated that every fourth child in Germany suffers from chronic pain with every twentieth suffering from extreme recurrent pain. The incidence of chronic pain in children and adolescents is increasing with headache, abdominal pain and musculoskeletal pain being the most frequent. The quality of life declines not only due to the pain but to relieving postural and psychological factors, such as fear and sadness. School attendance, social activities and hobbies are mostly affected. This review summarizes the background of chronic pain syndromes and introduces a multimodal therapeutic approach.     

Evaluation and management of pain in children with rheumatic diseases.

The evaluation and management of pain in children with rheumatic diseases are still in the early stages of empirical development. Nevertheless, with the advent of the PPQ, systematic research efforts are now underway to develop the reliability and validity of the PPQ's measurement characteristics for pediatric rheumatic diseases. With these developments, the inclusion of pediatric pain measurement as an essential outcome variable in controlled clinical trials should be advocated. The major points to be advocated by professionals who care for these children are (1) Children can accurately report their pain when age-appropriate measures are used; (2) pharmacologic treatment is not a sufficient condition for adequate pain management; (3) cognitive-behavior therapy techniques can facilitate children's coping with "breakthrough" recurrent musculoskeletal pain with no known side effects; and (4) adequate pain control should be viewed as a quality assurance issue, considered as another indicator of the adequacy of pediatric health care.     

ERCP术后胰腺炎的影响因素分析

目的探讨诊断性与治疗性ERCP术后引发AP的高危因素及防范措施。方法采用单因素及多因素变量分析方法，对54例行诊断与治疗性ERCP的患者进行队列研究。结果54例患者中，3例（5，6％）并发ERCP术后胰腺炎（PEP），其中1例为诊断性ERCP，2例为诊疗性ERCP，ERCP术后胰腺炎均为轻症，经内科综合治疗后均痊愈出院。与PEP相关的主要因素有多次插管、多次胰管造影、导丝多次进入胰管、导丝引导插管、术中腹痛、全胰管显影、既往有胰腺炎病史等。其中，多次插管、胰管多次造影以及术中腹痛为高危因素。结论PEP与患者自身因素及医师操作技术有关，有效避免或减少这些高危因素的发生可预防PEP。     

Barostat testing in children with functional gastrointestinal disorders

Children and adolescents with chronic defecation disorders and chronic abdominal pain without obvious organic etiology form a challenging group of patients for pediatric health-care professionals. The pathophysiologic mechanisms underlying such functional gastroenterology disorders are poorly understood. Research studies on the use of the barostat have been aimed to increase our knowledge in this area. Barostat testing allows defining visceral hyper- or hyposensitivity, contractility, and compliance of the gut. This review focuses on rectal barostat studies performed in children with abdominal pain, constipation, and fecal incontinence.     

Chronic nonmalignant pain: a challenge for patients and clinicians

Chronic pain is widely regarded as a condition that is triggered by various factors, including physical, socio-cultural and psychological deficiencies (that is, maladaptive beliefs). These factors are important in the development and maintenance of this unpleasant experience, which consequently requires a biopsychosocial treatment approach. Pain is a multifaceted sense, the perception of which is personal. Pain also depends on various circumstances, and therefore represents a challenge for the patient, as well for the treating physicians. Patients who suffer from long-lasting pain with a predominantly psychosocial component should be referred to specialized pain clinics for further diagnostic assessment and possible allocation to multidisciplinary pain programs. High-quality randomized controlled trials indicate that multidisciplinary pain programs represent the best therapeutic option for the management of patients with complaints associated with complex chronic pain. The prevalence and the costs--both direct and indirect--that are attributed to chronic pain are increasing; however, not enough is being done to sufficiently and effectively treat chronic pain. There is, therefore, a need for well-designed, interdisciplinary, internationally comparable, and widely distributed pain programs, both in outpatient and inpatient settings, to contribute to the prevention of some future pain diseases.     

A systematic review of treatments for the painful heel.

OBJECTIVE: To establish the efficacy for treatments of pain on the plantar aspect of the heel. METHODS: Systematic review of the published and unpublished literature. Electronic search of Medline, BIDS and the Cochrane database of clinical trials. An assessment of the quality of the reporting was made of studies included in the review. Main outcome measure: patients' pain scores. Study selection: randomized controlled trials, published or unpublished, that evaluated treatments used for plantar heel pain. Foreign language papers were excluded. RESULTS: Eleven randomized controlled trials were included in the review. These evaluated some of the most frequently described treatments (steroid injections and orthoses) and some experimental therapies (extracorporeal shock wave therapy and directed electrons). The methodological assessment scores of the published trials were low; small sample sizes and failure to conceal the treatment allocation from study participants prevents more definitive statements about the efficacy of treatments. In 10 of the included trials, patients in both the intervention and control arms reported improved pain scores at the final outcome measure. CONCLUSIONS: Although much has been written about the treatment of plantar heel pain, the few randomized controlled trials involve small populations of patients and do not provide robust scientific evidence of treatment efficacy.     

Yoga for low back pain: a systematic review of randomized clinical trials

It has been suggested that yoga has a positive effect on low back pain and function. The objective of this systematic review was to assess the effectiveness of yoga as a treatment option for low back pain. Seven databases were searched from their inception to March 2011. Randomized clinical trials were considered if they investigated yoga in patients with low back pain and if they assessed pain as an outcome measure. The selection of studies, data extraction and validation were performed independently by two reviewers. Seven randomized controlled clinical trials (RCTs) met the inclusion criteria. Their methodological quality ranged between 2 and 4 on the Jadad scale. Five RCTs suggested that yoga leads to a significantly greater reduction in low back pain than usual care, education or conventional therapeutic exercises. Two RCTs showed no between-group differences. It is concluded that yoga has the potential to alleviate low back pain. However, any definitive claims should be treated with caution.     

Role of antispasmodics in the treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a long-lasting, relapsing disorder characterized by abdominal pain/discomfort and altered bowel habits. Intestinal motility impairment and visceral hypersensitivity are the key factors among its multifactorial pathogenesis, both of which require effective treatment. Voltage-gated calcium channels mediate smooth muscle contraction and endocrine secretion and play important roles in neuronal transmission. Antispasmodics are a group of drugs that have been used in the treatment of IBS for decades. Alverine citrate, a spasmolytic, decreases the sensitivity of smooth muscle contractile proteins to calcium, and it is a selective 5-HT_1A receptor antagonist. Alverine, in combination with simethicone, has been demonstrated to effectively reduce abdominal pain and discomfort in a large placebo-controlled trial. Mebeverine is a musculotropic agent that potently blocks intestinal peristalsis. Non-placebo-controlled trials have shown positive effects of mebeverine in IBS regarding symptom control; nevertheless, in recent placebo-controlled studies, mebeverine did not exhibit superiority over placebo. Otilonium bromide is poorly absorbed from the GI tract, where it acts locally as an L-type calcium channel blocker, an antimuscarinic and a tachykinin NK2 receptor antagonist. Otilonium has effectively reduced pain and improved defecation alterations in placebo-controlled trials in IBS patients. Pinaverium bromide is also an L-type calcium channel blocker that acts locally in the GI tract. Pinaverium improves motility disorders and consequently reduces stool problems in IBS patients. Phloroglucinol and trimethylphloroglucinol are non-specific antispasmodics that reduced pain in IBS patients in a placebo-controlled trial. Antispasmodics have excellent safety profiles. T-type calcium channel blockers can abolish visceral hypersensitivity in animal models, which makes them potential candidates for the development of novel therapeutic agents in the treatment of IBS.     

Pediatric heart transplantation: immunosuppression and its complications

PURPOSE OF REVIEW: Advances in immunosuppression have contributed to the significant improvements in outcome for pediatric heart transplant recipients in the past two decades. The large increase in the number of available immunosuppressive agents in the past few years mandates that those caring for this complex group of patients remain up to date in this rapidly advancing field. RECENT FINDINGS: In this review, we evaluate recent studies of immunosuppressive efficacy, end-organ toxicities, and side effects of nonspecific immunosuppression with currently used regimens. In addition, we examine new findings that attempt to define the genetic contribution to rejection profiles, immunosuppressive efficacy, and drug disposition after heart transplantation in children. SUMMARY: The continuous evaluation of new immunosuppressive regimens will help to elucidate the optimal treatment regimens for pediatric heart transplant recipients. Unfortunately, the small number of transplantations means that it is unlikely that pivotal randomized, controlled trials will ever be performed in this population. Extrapolation from adult controlled trials and experience from other pediatric solid organ transplant recipient populations will continue to provide important contributions to our knowledge base. Understanding the genetic contribution to graft and patient outcomes may help us tailor immunosuppressive therapy for the individual patient.     

Acupuncture for chronic pelvic pain in patients with SPID: A protocol for systematic review and meta-analysis

Background:Chronic pelvic pain (CPP) is one of the common sequela of pelvic inflammatory disease, the pathological factors are adhesions, scarring and pelvic congestion which caused by inflammation, often cause abdominal pain and lumbosacral soreness, and aggravated after fatigue, sexual intercourse and during menstruation. It is difficult to treat because special pathological changes. Although acupuncture has gained increased popularity for the management of CPP, evidence regarding its efficacy is lacking. Therefore, a systematic review of acupuncture for chronic pelvic pain in patients with SPID is required to provide available evidence for further study.Methods and analysis:We will conduct a systematic review of randomized controlled trials (RCTs) that investigate the effect and safety of acupuncture for the treatment of chronic pelvic pain patients with SPID. We will electronically search the literature in the databases of PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, the Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Digital Periodicals, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP) and select eligible articles. Data extraction will be conducted by 2 researchers independently, and risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. The primary outcomes will be total effective rate and VAS pain score, and the secondary outcomes include the recurrence rate and adverse reaction. All data analysis will be conducted by software Review Manager V.5.3.Results:This study will provide the latest analysis of the currently available evidence for the efficacy of acupuncture for chronic pelvic pain in patients with SPID.PROSPERO registration number:CRD42020193826.