Therapeutic alliance impact on analgesic outcomes in a real-world clinical setting: An observational study

A good therapeutic alliance is relevant for healthcare providers exposed to patients\u27 suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40–70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80±75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the healthcare providers, they “gained new insight”, “felt better”, or “felt content with their doctor’s treatment”. What´s more, patients who affirmed “I benefit from the treatment” experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients

Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences

ntroduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process. Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0-100 mm), global activity (GAF, 0-100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0-96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed. Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20-123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6-11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = -0.604, p < 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men. Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction

Evolution of the consumption of lorazepam in a rural environment in the Region of Murcia (2012-2018)

Objective: To evaluate the consumption of lorazepam in the Region of Murcia, specifically in the district of Mula, during the period 2012-2018, considering age and sex variables. Method: Cross-sectional descriptive study, where the use of benzodiazepines in a specific population during the period 2012 - 2018 is investigated. The variables collected were sex, age and the prescribed Defined Daily Dose. The data correspond to the dispensations of Lorazepam in the pharmacy offices of the disctrict of Mula, provided by the Health Assistance General Directorate. Daily dose per inhabitant and per 1000 inhabitants were calculated and the groups median and interquartile ranges were established p25 and p75 for later comparisons. Results: Overall consumption over the period increased by 0.42%. In men it increased by 21.4%, while in women it decreased by 7.5%. However, in women, consumption was at higher doses, betwand significant differences were found in lorazepam consumption een groups when analyzed by sex. The analysis by age showed a significant increase in consumption as the age of the patients increased. Conclusion: The consumption of benzodiazepines is high with increasing age, more so in women, and this may have an impact on the adverse effects associated with this group of drugs and present an important public health problem

Evolution of the consumption of lorazepam in a rural environment in the Region of Murcia (2012-2018)

Objective: To evaluate the consumption of lorazepam in the Region of Murcia, specifically in the district of Mula, during the period 2012-2018, considering age and sex variables. Method: Cross-sectional descriptive study, where the use of benzodiazepines in a specific population during the period 2012 - 2018 is investigated. The variables collected were sex, age and the prescribed Defined Daily Dose. The data correspond to the dispensations of Lorazepam in the pharmacy offices of the disctrict of Mula, provided by the Health Assistance General Directorate. Daily dose per inhabitant and per 1000 inhabitants were calculated and the groups median and interquartile ranges were established p25 and p75 for later comparisons. Results: Overall consumption over the period increased by 0.42%. In men it increased by 21.4%, while in women it decreased by 7.5%. However, in women, consumption was at higher doses, betwand significant differences were found in lorazepam consumption een groups when analyzed by sex. The analysis by age showed a significant increase in consumption as the age of the patients increased. Conclusion: The consumption of benzodiazepines is high with increasing age, more so in women, and this may have an impact on the adverse effects associated with this group of drugs and present an important public health problem

Monitorización Circadiana Ambulatoria y nuevos marcadores biomoleculares para el estudio del sueño en adultos con Trastorno del Espectro Autista (TEA) y discapacidad intelectual

Introduction: Sleep problems are a common and permanent condition in autism spectrum disorder (ASD), also when intellectual disability (ID) is present. Causes remain unknown, but are likely multifactorial, which means that both genetic and environmental factors may play a role in their prevalence. Increasing knowledge of sleep assessment tools would help to test effectiveness of treatments for the most prevalent sleep problems in ASD: insomnia and Circadian Rhythm Sleep-Wake Disorders (CRSWDs). Aims: This work aimed to evaluate the use of ambulatory circadian monitoring (ACM), in adults with ASD and ID, as an objective tool to report sleep problems, to test agomelatine effectiveness as a sleep treatment, and to analyse the influence of circadian clock and melatonin pathway genes as potential molecular biomarkers for sleep problems. Methods: A prospective study (AGOTEA) was conducted using ACM (7 days, 24-hour recording) to analyse sleep-wake cycle in adults with ASD and ID (n=41) vs. controls (n=51). Then, participants with persistent sleep problems (n=23, insomnia and CRSWDs, according to International Classification of Sleep Disorders-Third Edition criteria), were included in a randomized, crossover, triple-blind, placebo-controlled clinical trial (AGOTEA-CT), to evaluate agomelatine (25mg/day, 3-months) effectiveness. Finally, an observational study (GENTEA, n=83), using ACM and Sequenom MassARRAY, analyzed genetic variants (PER1, ASMT, NPAS2, and MTNR1A) influence on sleep. Statistical data were analyzed by R 3.2.4 and Graph Pad Prism 5.0 software. Results: Sleep parameters were only in normal range values in 16% of adults with ASD and ID. They showed significantly higher insomnia symptoms (low sleep efficiency, prolonged sleep latency and increased number and length of night awakenings) and signs of an advanced sleep-wake phase disorder. Autistic adults had a pattern of daily sedentary behaviour and increased nocturnal activity. Agomelatine significantly increased a mean of 83 minutes the total sleep time at night, corrected the temperature phase and improved sleep rhythm stability. Circadian clock gene PER1 (rs885747, rs6416892) presented a different genotype distribution in autistic participants compared to controls. Rs6416892-G allele had better sleep pattern, together with a phase advancement of sleep and wrist temperature circadian rhythms. Conclusions: ACM was effective and accurate in measuring sleep-wake cycle in autistic adults with ID. Agomelatine could be appropriate for the synchronization of circadian rhythms, improving sleep quantity and quality. There is a need for further clinical studies to confirm agomelatine effectiveness and the use of circadian clock and melatonin pathway genes as new molecular biomarkers for sleep problems in ASD.Introducción: Una persona con trastorno del espectro autista puede, de forma común y a lo largo de toda su vida, sufrir problemas de sueño, incluso cuando existe un diagnóstico de discapacidad intelectual asociado. Las causas de éstos son todavía desconocidas, pero probablemente sean multifactoriales, lo que significa que los factores genéticos y ambientales podrían jugar un papel en su prevalencia. Por tanto, investigar sobre las herramientas para evaluar el sueño ayudaría a valorar la eficacia de los tratamientos para los problemas de sueño más prevalentes en el trastorno del espectro autista: insomnio y trastornos del ritmo circadiano. Objetivos: Evaluar en adultos con trastorno del espectro autista y discapacidad intelectual el uso de la monitorización circadiana ambulatoria como herramienta objetiva para determinar los problemas del sueño, la eficacia farmacológica de la agomelatina para mejorar el sueño, y la influencia de los genes reloj y de la ruta de la melatonina como posibles marcadores biomoleculares de los problemas de sueño. Métodos: Se realizó un estudio prospectivo (AGOTEA) para analizar el ciclo de sueño-vigilia en adultos con trastorno del espectro autista y discapacidad intelectual (n=41) frente a controles (n=51) utilizando monitorización circadiana ambulatoria (7 días, registro continuo de 24 horas). Luego, aquellos participantes con problemas persistentes de sueño (n=23, insomnio y trastornos del ritmo circadiano, según criterios de la tercera Edición de la Clasificación Internacional de Trastornos del Sueño), se incluyeron en un ensayo clínico aleatorizado, cruzado, triple ciego, controlado con placebo (AGOTEA-CT), para evaluar la eficacia de la agomelatina (25mg/día, 3 meses). Finalmente, un estudio observacional (GENTEA, n=83), utilizando Sequenom MassARRAY y monitorización circadiana ambulatoria, analizó la influencia de las variantes genéticas (PER1, ASMT, NPAS2 y MTNR1A) en el sueño. El análisis estadístico se realizó con el software R 3.2.4 y Graph Pad Prism 5.0. Resultados: Sólo el 16% de los adultos con autismo y discapacidad intelectual tuvo los parámetros de sueño dentro del rango normal. Tuvieron significativamente más síntomas de insomnio (baja eficiencia del sueño, latencia prolongada y aumento del número y la duración de los despertares nocturnos) e indicios de un adelanto en la fase del sueño. Además, eran más sedentarios durante el día y activos por la noche. La agomelatina aumentó significativamente el tiempo de sueño nocturno una media de 83 minutos, corrigió el ritmo de temperatura y mejoró la estabilidad del sueño. El gen reloj circadiano PER1 (rs885747, rs6416892) presentó una distribución de genotipo diferente en los adultos con autismo comparada a la de los controles. El alelo G del rs6416892 tuvo un mejor patrón de sueño, así como un adelanto de fase del ritmo circadiano de sueño y temperatura periférica. Conclusiones: Para la medición del ciclo de sueño-vigilia en adultos con trastorno del espectro autista y discapacidad intelectual, la monitorización circadiana ambulatoria fue efectiva y precisa. El uso de agomelatina podría ser apropiado para sincronizar los ritmos circadianos, e incrementar la calidad y cantidad de sueño. Para confirmar su eficacia y el uso de genes reloj circadianos y de la ruta de la melatonina como nuevos marcadores biomoleculares de los problemas de sueño en el trastorno del espectro autista, hay que llevar a cabo más estudios clínicos

Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients

The threats involved in the long-term opioid treatment of chronic non-cancer pain (CNCP) have increased notably. Strategies to identify at-risk patients are important because there is no clear evidence showing which screening or deprescription programmes are appropriate. Our aim was to evaluate the evidence provided by pharmacogenetics applied to predict an analgesic toxicity profile in prescription opioid use disorder (POUD) patients participating in an opioid deprescription programme. Pharmacogenetic markers were analysed in an observational, prospective deprescription programme for POUD patients (n = 88) treated for CNCP. It consisted of monitoring visits (baseline, follow-up and final), opioid rotation or discontinuation and the recording of adverse events and suspected adverse drug reactions (ADRs). Variants in OPRM1 (A118G), ABCB1 (C3435T), COMT (G472A), OPRD1 (T921C) and ARRB2 (C8622T) genes were tested by real-time PCR. Ethics committee approved the study. Wild-type OPRM1-AA genotype carriers reported a significantly higher number of adverse events than OPRM1-AG/GG (median [p25-75], 7 [5-11] vs 5 [3-9]), particularly gastrointestinal system events (90% vs 63%) such as nausea (33% vs 0%). Suspected ADRs (affecting 17% of the patients) were three times higher in males than in females (30% vs 11%). The deprescription programme was effective and safe, and it achieved a significant progressive reduction in the morphine equivalent daily dose, strong opioids and other analgesics' use, without causing any changes in pain intensity or opiate abstinence syndrome. OPRM1 gene polymorphisms could identify the risk of gastrointestinal adverse events in POUD patients. Deprescription programmes including pharmacogenetic analysis should be considered during the follow-up of this population

Global Pain State Questionnaire: Reliability, Validity, and Gender Gap

Objective: To quantify patients’ pain more objectively is essential to guide an individualized therapy, all the more so in patients under long-term opioid-use. Only a thoughtful and objective understanding of risks and benefits could improve an individualized standard of care. Our aim was to assess metric reliability and validity of an integrated and self-report Global Pain Status questionnaire to quantify the impact of pain on patient’s health in a more precise manner. Methods: A cross-sectional study was conducted to analyse the reliability, agreement, and validity of an integrated questionnaire compared to isolated scales, due to kappa statistics, intra- class and other correlation coefficients. Level of pain (intensity and relief), quality of life, most prevalent analgesic adverse events and hospital frequentation were registered in a total of 38 cases (pain unit patients) and 52 painless matched-controls.. A reduced multitrait-multimethod matrix and a canonical-correlation analysis were developed together with a multiple linear regression. Results: Cases (56 ± 10 years old, 63% females, pain intensity 66 ± 23 mm, incidence rate of 5 adverse events) represented a regular pain population. A high intraobserver correlation (r0.75- 0.88, weighted-κ 0.41–0.51, unweighted-κ 0.66-0.82) was evidenced together with significant correlation coefficients in test-retest reliability, and for validity, even more, in a reduced multitrait-multimethod matrix (>0.8) and canonical-correlation (>0.95). A gender gap was evidenced in cases’ companions, mostly middle-aged females (78%), who experienced negative effects on their health. Conclusions: The Global Pain Status questionnaire is an evaluation instrument with enough reliability and validity, being a low-cost method to determine the multidimensional pain management at clinical routine. A gender-gap within pain caregivers was found that affect their health outcomes. Support interventions for pain patients’ companions should consider specific gender risk factors

Therapeutic alliance impact on analgesic outcomes in a real-world clinical setting: An observational study

A good therapeutic alliance is relevant for healthcare providers exposed to patients’ suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40–70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80 ± 75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they “gained new insight”, “felt better”, or “felt content with their doctor’s treatment”. What´s more, patients who affirmed “I benefit from the treatment” experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients

Incidence of pertussis in persons ≤15 years of age in Valencia, Spain: seroprevalence of antibodies to pertussis toxin (PT) in children, adolescents and adults

The aim is to determine the incidence of pertussis in persons ≤15 years in age in Valencia, Spain. To assess the prevalence of IgG antibodies to pertussis toxin (PT) in children, adolescents and adults.Medicin