Efectividad y farmacogenética en un protocolo de desprescripción en pacientes con dolor crónico y dependencia iatrogénica a opioides / Effectiveness and pharmacogenetics in a deprescription protocol in chronic pain patients and iatrogenic opioid dependence

Los protocolos de desprescripción deberían formar parte del cuidado de pacientes con dolor crónico no oncológico que hayan desarrollado dependencia iatrogénica a opioides. Nuestro objetivo es evaluar la implantación de un protocolo de desprescripción individualizado (PDI) incluyendo marcadores farmacogenéticos. Se llevó a cabo un estudio observacional prospectivo, de 6 meses de seguimiento con pacientes con dependencia iatrogénica a opioides (n=88). Una vez finalizado el PDI, los pacientes se agruparon en "respondedores" o "no respondedores" al protocolo. Las variantes de los genes OPRM1 (A118G), OPRD1 (T921C), COMT (G472A), ABCB1 (C3435T), ARRB2 (C8622T) y CYP2D6 se determinaron por PCR a tiempo real. Al concluir el estudio, el PDI alcanzó un 64% de respondedores con una reducción de dosis equivalente de morfina diaria (DEMD) significativa (visita basal vs. final, 167 vs. 87 mg/día, p=0.007) sin presentar síndrome de abstinencia, manteniendo un dolor, alivio, calidad de vida y funcionalidad moderados. El porcentaje de pacientes usando buprenorfina o sin opioides fue significativamente mayor en la visita final (65% vs. 22%, p<0.001). Los portadores del genotipo nativo 118-AA OPRM1 requirieron una DEMD menor en la visita inicial (modelo dominante, p=0.018 y superdominante, p=0.020) y en la final (modelo codominante, p=0.032 y recesivo, p=0.032). Nuestro PDI mostró efectividad y seguridad reduciendo la DEMD con una buena conversión a buprenorfina, especialmente en pacientes con genotipo 118-AA OPRM1

Deprescription protocols should be part of chronic non-cancer pain patients’ care in those cases where iatrogenic dependence is present. Our aim is to assess the implementation of a individualized deprescription protocol (IDP) including pharmacogenetic markers. An observational prospective study was carried out in patients presenting prescription opioid dependence (n=88) during 6 months of followup. Once the IDP was ended, patients were grouped in "responders" or "non-responders" to IDP. Genetic variants from OPRM1 (A118G), OPRD1 (T921C), COMT (G472A), ABCB1 (C3435T) and ARRB2 (C8622T) and CYP2D6 genes, were determined by real time PCR. At the end of the study, PDI achieved a 64 % of responders with a significant morphine equivalent daily dose (MEDD) reduction (basal visit vs. final, 167 vs. 87 mg/day, p=0.007) without presenting opiate withdrawal syndrome, keeping a moderate pain intensity, pain relief, quality of life and functionality. Frequency of patients using buprenorphine or without opioids was significantly higher in the last visit than in basal visit (65 % vs. 22 %, p<0.001). Carriers of wild type genotype 118-AA OPRM1 required lower MEDD in the basal visit (dominant, p=0.018 and overdominant models, p=0.020) and in the final visit (codominant, p=0.032 and recessive models, p=0.032). Our IDP showed efectiveness and security in reducing MEDD with a good conversion to buprenorphine, even more in naïve 118-AA OPRM1 genotype

Repeatability and accuracy testing of a weight distribution platform and comparison to a pressure sensitive walkway to assess static weight distribution.

OBJECTIVE: To evaluate the accuracy and repeatability of measurements collected using a weight distribution platform and a pressure sensitive walkway using an inanimate object with known weight distribution. METHODS: A custom-built jig with a range of weights was applied in a random order. Measurements were collected on both devices and compared to each other and to the known weight distribution. RESULTS: Weight distribution platform and pressure sensitive walkway measurements were highly correlated to each other (Pearson's correlation coefficient R = 0.98) and to actual weights (R = 0.99 for the weight distribution platform; 0.98 for the pressure sensitive walkway). Repeatability from day to day for both devices was greater than 0.99. For the weight distribution platform, the 95% confidence interval was ± 2.5% from the true percentage and ± 3.3% for the pressure sensitive walkway. The coefficient of variation (COV) was highest for both devices at the lightest weights (weight distribution platform 11.28%, pressure sensitive walkway 16.91%) and lowest with the heaviest weights (weight distribution platform 3.71%, pressure sensitive walkway 5.86%). CONCLUSION: Both the weight distribution platform and the pressure sensitive walkway provided accurate and consistent measures of weight distribution with no significant difference between devices. The rounded standard error was three percent for the weight distribution platform, and four percent for the pressure sensitive walkway. The higher variability when measuring the smallest weight suggests less accuracy at lower weights with both devices. CLINICAL SIGNIFICANCE: The weight distribution platform is a repeatable and accessible device to measure static weight distribution, and if proven the same in a clinical setting, it will be a valuable addition to current objective measures of limb use.

Initial evaluation of nighttime restlessness in a naturally occurring canine model of osteoarthritis pain.

Chronic pain due to osteoarthritis (OA) can lead to significant disruption of sleep and increased restlessness. Our objective was to assess whether naturally occurring canine OA is associated with nighttime restlessness and so has potential as a model of OA-associated sleep disturbance. The study was designed as a two-part prospective masked, placebo-controlled study using client-owned dogs (Part A n = 60; Part B n = 19). Inclusion criteria consisted of OA-associated joint pain and mobility impairment. The primary outcome measure for both parts was nighttime accelerometry. In Part B, quality of sleep was assessed using a clinical metrology instrument (Sleep and Night Time Restlessness Evaluation Score, SNoRE). Part A included dogs receiving two weeks of non-steroidal anti-inflammatory drug (NSAID) preceded with two weeks of no treatment. Part B was a crossover study, with NSAID/placebo administered for two weeks followed by a washout period of one week and another two weeks of NSAID/placebo. Repeated measures analysis of variance was used to assess differences between baseline and treatment. There were no significant changes in accelerometry-measured nighttime activity as a result of NSAID administration. SNoRE measures indicated significant improvements in aspects of the quality of nighttime sleep that did not involve obvious movement. These results reflect the few similar studies in human OA patients. Although accelerometry does not appear to be useful, this model has potential to model the human pain-related nighttime sleep disturbance, and other outcome measures should be explored in this model.

Relationship between mechanical thresholds and limb use in dogs with coxofemoral joint oa-associated pain and the modulating effects of pain alleviation from total hip replacement on mechanical thresholds.

OBJECTIVES: To compare von Frey mechanical quantitative sensory thresholds (mQSTvF ) between pelvic limbs in dogs before unilateral total hip replacement (THR) surgery; to correlate ground reaction forces (GRF) with mQSTvF ; to assess changes in mQSTvF after THR surgery. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n = 44). METHODS: mQSTvF and GRF measured using a pressure sensitive walkway were evaluated before, and 3, 6, and 12 months after, unilateral THR. Measurements were recorded from the affected (operated) pelvic limb (APL) and the non-operated pelvic limb (NPL). Random effects analysis and forwards stepwise linear regression models were used to evaluate the influence of time since surgery and patient factors on mQSTvF thresholds. RESULTS: There were no significant correlations between mQSTvF data and age, bodyweight or the GRF variables. Preoperative mQSTvF measured at the APL and NPL did not differ (P = .909). mQSTvF thresholds increased significantly after 12 months in NPL (P = .047) and APL (P = .001). In addition to time, APL mQSTvF values were significantly affected by sex (higher in males, P = .010) and body condition score (higher in leaner dogs, P = .035) and NPL mQSTvF values by sex (P = .038). CONCLUSION: Successful unilateral THR results in decreased central sensitization after 12 months.