The Use of Conditioning Open-Label Placebo in Opioid Dose Reduction: A Case Report and Literature Review.

Introduction: Adequate pain management for inpatients in rehabilitation units is essential for achieving therapeutic goals. Opioid treatments are commonly prescribed, but these are associated with numerous adverse effects, including the risk of addiction and decreased quality of life. Conditioning an open-label placebo is a promising approach to extend the analgesic effect of the opioid while reducing its overall dosage. Objectives: To describe a patient's experience in using conditioning open-label placebo (COLP) as a pharmaco-behavioral intervention to decrease opioid intake and its side effects after inpatient rehabilitation discharge, and to perform a literature review about the use of open-label placebo in pain. Methods: This case study has been extracted from a clinical trial initiated in 2018. A 61-year-old male was recruited at a tertiary rehabilitation hospital after suffering a traumatic sport-related injury and orthopedic surgery. Pain management included prescription of non-steroidal anti-inflammatory drugs (NSAIDs) and short-acting oxycodone. After trial participation, the patient requested off-label COLP treatment to help him decrease outpatient opioid utilization. Results: After COLP treatment, the patient could discontinue oxycodone intake (a reduction from 15 morphine equivalents/day) after rehabilitation discharge. Moreover, opioid side effects decreased from 46 to 9 points on the numerical opioid side-effects scale. A literature review identified five clinical trials using "honest" open-label placebo (OLP) or COLP as an experimental intervention for pain control. From these studies, two were in the area of chronic lower back pain, one in post spine surgery, one in irritable bowel syndrome, and another in spinal cord injury and polytrauma. Four studies reported positive outcomes related to pain control, while one study showed no significant differences in pain management between treatment-as-usual and the COLP group. Conclusion: The case report illustrates how a pharmaco-behavioral intervention can facilitate downward opioid titration safely after inpatient rehabilitation. It initiates a discussion about new approaches for opioid management using conditioning and the patient's expectation of pain relief.

Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control.

Opioid consumption for those in comprehensive inpatient rehabilitation units is high because of the complexity of their injuries. Notably, pain in rehabilitation leads to worsened clinical outcomes because of maladaptive behaviors and poor engagement during therapies. It is critical to developing evidence-based pharmacobehavioral interventions. Based on principles of classical conditioning, conditioning open-label placebo (COLP) is a promising approach for reducing opioid use in comprehensive inpatient rehabilitation, and this technique takes advantage of the possibility of association learning and opioid pharmacology to promote evoked placebo-driven analgesia. OBJECTIVES: In this brief report, we evaluate the feasibility of COLP as a pharmacobehavioral intervention to decrease total opioid consumption in patients with pain hospitalized at Spaulding Rehabilitation Hospital. METHODS: Inpatients with spinal cord injury and polytrauma (n = 20) with moderate to severe pain were randomized to receive COLP (n = 10) or treatment-as-usual for 6 consecutive days. Opioid utilization was measured by morphine equivalents using the morphine equivalent dose conversion; pain severity was assessed using the numerical visual analog scale. RESULTS: Conditioning open-label placebo significantly reduced total opioid consumption by the end of the intervention period (P ≤ 0.001). Pain reduction was also significant for the COLP group (P = 0.005), whereas the treatment-as-usual group demonstrated a trend towards pain reduction (P = 0.05). CONCLUSIONS: This study presents the first data in the use of a pharmacobehavioral intervention that capitalize on the benefits of open-label placebo and classical drug conditioning for opioid dose reduction in a population with moderate to severe pain exposed to intensive inpatient rehabilitation.

Optimised transcranial direct current stimulation (tDCS) for fibromyalgia-targeting the endogenous pain control system: a randomised, double-blind, factorial clinical trial protocol.

INTRODUCTION: Fibromyalgia (FM) is a common debilitating condition with limited therapeutic options. Medications have low efficacy and are often associated with adverse effects. Given that FM is associated with a defective endogenous pain control system and central sensitisation, combining interventions such as transcranial direct current stimulation (tDCS) and aerobic exercise (AE) to modulate pain-processing circuits may enhance pain control. METHODS AND ANALYSIS: A prospective, randomised (1:1:1:1), placebo-controlled, double-blind, factorial clinical trial will test the hypothesis that optimised tDCS (16 anodal tDCS sessions combined with AE) can restore of the pain endogenous control system. Participants with FM (n=148) will undergo a conditioning exercise period and be randomly allocated to one of four groups: (1) active tDCS and AE, (2) sham tDCS and AE, (3) active tDCS and non-aerobic exercise (nAE) or (4) sham tDCS and nAE. Pain inhibitory activity will be assessed using conditioned pain modulation (CPM) and temporal slow pain summation (TSPS)-primary outcomes. Secondary outcomes will include the following assessments: Transcranial magnetic stimulation and electroencephalography as cortical markers of pain inhibitory control and thalamocortical circuits; secondary clinical outcomes on pain, FM, quality of life, sleep and depression. Finally, the relationship between the two main mechanistic targets in this study-CPM and TSPS-and changes in secondary clinical outcomes will be tested. The change in the primary efficacy endpoint, CPM and TSPS, from baseline to week 4 of stimulation will be tested with a mixed linear model and adjusted for important demographic variables. ETHICS AND DISSEMINATION: This study obeys the Declaration of Helsinki and was approved by the Institutional Review Board (IRB) of Partners Healthcare under the protocol number 2017P002524. Informed consent will be obtained from participants. Study findings will be reported in conferences and peer-reviewed journal publications. TRIAL REGISTRATION NUMBER: NCT03371225.

Factores de riesgo para mortalidad por neumonia adquirida en la comunidad en niños hospitalizados menores de cinco años. Instituto Nacional de Salud del Niño / Risk factors for mortality from community-acquired pneumonia in hospitalized children under five. National Institute of Child Health

Introducción: La neumonía adquirida en la comunidad (NAC) constituye la primera causa de mortalidad en niños menores de cinco años a nivel mundial. En nuestro país, a pesar de su gran prevalencia se dispone de poca información respecto a los factores de riesgo para mortalidad en dicha población. Objetivo: Determinar los factores de riesgo para mortalidad en pacientes menores de cinco años con neumonía adquirida en la comunidad, hospitalizados en el Instituto Nacional de Salud del Niño (INSN), Lima-Perú. Material y métodos: Estudio de casos y controles. Se evaluaron 197 historias (63 casos y 134 controles) de pacientes menores de 5 años ingresados con diagnóstico de ingreso de NAC al INSN. Las características epidemiológicas, y clínicas de cada paciente, así como los resultados de exámenes auxiliares fueron evaluados mediante estadística descriptiva y análisis bivariado. Aquellos factores que alcanzaron significancia estadística en este último fueron evaluados mediante regresión logística. Resultados: Mediante el análisis bivariado se encontró significancia estadística respecto a la edad de los pacientes (p <0,001), el antecedente de bajo peso al nacer (p=0,04; OR: 2,79), la falta de alimentación durante el tiempo de enfermedad (p<0,001; OR: 6,2), la saturación de oxígeno (p=0,01; OR: 2,52) Y la severidad de la neumonía (p<0,001). En el análisis multivariado se encontró significancia estadística respecto a la falta de alimentación durante el tiempo de enfermedad (p=0, 008; OR: 4,92) Y la severidad del cuadro, encontrándose dentro de esta última que la categoría de neumonía "Muy severa" es la más relacionada a la mortalidad (p<0,001; OR: 87,17).Conclusiones: La falta de alimentación durante el tiempo de enfermedad y el diagnóstico de ingreso de neumonía muy severa, definida de acuerdo a los parámetros de la OMS, constituyen factores de riesgo para mortalidad por NAC en pacientes menores de 5 años

Introduction: Community-acquired pneumonia (CAP) is the wortdwide leading cause of mortality in children under 5 years old. In our country, des pite its high prevalence there is little information regarding risk factors for mortality in this population. Objective: T o determine risk factors for mortality in patients less than 5 years old with community-acquired pneumonia hospitalized at the Instituto Nacional de Salud del Nino (INSN), Lima-Peru. Materials and Methods: Case-control study. 197 medical historys were evaluated (63 cases and 134 controls) of patients younger than 5 years old hospitalized with admission diagnosis of CAP at the INSN. The epidemiological and clinical data and auxiliary test results were evaluated by descriptive statistics and bivariate analysis. Those factors that were statistically significant in the latter were evaluated using logistic regression. Results: By using bivariate analysis statistical significance was found regarding the age of the patients (p <0.001), history of low birth weight (p = 0.04, OR: 2.79), lack of feeding during the time of iIIness (p <0.001, OR: 6.2), oxygen saturation (p=0, 01; OR: 2, 52) and severity of pneumonia (p <0.001). In multivariate analysis, statistical significance was found regarding the lack of feeding during the time of illness (p = 0.008, OR: 4.92) and the severity of the disease, the latter being found within the category of "very severe" pneumonia, as the most related to mortality (p <0.001, OR: 87.17). Conclusions: The lack of feeding during the time of iIIness and admission diagnosis of very severe pneumonia, defined according to WHO standards, are risk factors for mortality in CAP in patients under 5 years old