Sex-Differences in Pain and Opioid Use Disorder Management: A Cross-Sectional Real-World Study

Background: It is essential to focus attention on sex-specific factors which are clinically relevant in pain management, especially with regards to opioid use disorder (OUD) risk. The aim of this study was to explore potential sex-differences in chronic non-cancer pain (CNCP) outpatients. (2) Methods: An observational cross-sectional study was conducted under CNCP outpatients with long-term prescribed opioids (n = 806), wherein 137 patients had an OUD diagnosis (cases, 64% females) and 669 did not (controls, 66% females). Socio-demographic, clinical, and pharmacological outcomes were analyzed. (3) Results: Female controls presented an older age and less intensive pain therapy but higher psychotropic prescriptions and emergency department visits compared to male controls. Meanwhile, cases demonstrated a younger age, higher work disability, double morphine equivalent daily dose, and benzodiazepine use compared with controls. Here, female cases showed an 8% greater substance use disorder (OR 2.04 [1.11-3.76]) and 24% lower tramadol use, while male cases presented a 22% higher fentanyl use (OR 2.97 [1.52-5.81]) and reported the highest number of adverse drug reactions (24%, OR 2.40 [1.12-5.16]) compared with controls. (4) Conclusions: An OUD individual risk profile was evidenced with sex-differences to take into consideration to design equal prevention programs

Mindfulness and job control as moderators of the relationships between demands and innovative work behaviours

Innovation enables organizations to respond successfully to rapid changes in a business environment. This innovation capability largely relies on employees. Although workers are required to be innovative, their jobs frequently contain higher demands that might make it difficult for them to innovate at work. The Job Demands-Control model active hypothesis suggests that highly demanding jobs that allow individuals enough discretion enhance innovative performance. Improving an important attentional resource such as mindfulness at work might also play a similar role, although there is a need for more research at this level. The main aim of this study is to examine the relative contribution of job control and increases in mindfulness as moderators in the job demands-innovation work behaviours relationship. The results obtained with 221 workers indicated that in previous situations characterized by high job demands (T1), workers who increase their capacity for mindfulness are more innovative in the future (T2)

Pharmacogenetic Guided Opioid Therapy Improves Chronic Pain Outcomes and Comorbid Mental Health: A Randomized, Double-Blind, Controlled Study

Interindividual variability in analgesic response is at least partly due to well-characterized polymorphisms that are associated with opioid dosing and adverse outcomes. The Clinical Pharmacogenetics Implementation Consortium (CPIC) has put forward recommendations for the CYP2D6 phenotype, but the list of studied drug-gene pairs continues to grow. This clinical trial randomized chronic pain patients (n = 60), referred from primary care to pain unit care into two opioid prescribing arms, one guided by CYP2D6, μ-opioid receptor (OPRM1), and catechol-O-methyl transferase (COMT) genotypes vs. one with clinical routine. The genotype-guided treatment reduced pain intensity (76 vs. 59 mm, p < 0.01) by improving pain relief (28 vs. 48 mm, p < 0.05), increased quality of life (43 vs. 56 mm p < 0.001), and lowered the incidence of clinically relevant adverse events (3 [1-5] vs. 1 [0-2], p < 0.01) and 42% opioid dose (35 [22-61] vs. 60 [40-80] mg/day, p < 0.05) as opposed to usual prescribing arm. The final health utility score was significantly higher (0.71 [0.58-0.82] vs. 0.51 [0.13-0.67] controls, p < 0.05) by improving sleepiness and depression comorbidity, with a significant reduction of 30-34% for headache, dry mouth, nervousness, and constipation. A large-scale implementation analysis could help clinical translation, together with a pharmaco-economic evaluation

Opioid Monitoring in Clinical Settings: Strategies and Implications of Tailored Approaches for Therapy

This review emphasises the importance of opioid monitoring in clinical practice and advocates for a personalised approach based on pharmacogenetics. Beyond effectively managing pain, meticulous oversight is required to address concerns about side effects, specially due to opioid-crisis-related abuse and dependence. Various monitoring techniques, along with pharmacogenetic considerations, are critical for personalising treatment and optimising pain relief while reducing misuse and addiction risks. Future perspectives reveal both opportunities and challenges, with advances in analytical technologies holding promise for increasing monitoring efficiency. The integration of pharmacogenetics has the potential to transform pain management by allowing for a precise prediction of drug responses. Nevertheless, challenges such as prominent pharmacogenetic testing and guideline standardisation persist. Collaborative efforts are critical for transforming scientific advances into tangible improvements in patient care. Standardised protocols and interdisciplinary collaboration are required to ensure consistent and evidence-based opioid monitoring. Future research should look into the long-term effects of opioid therapy, as well as the impact of genetic factors on individual responses, to help guide personalised treatment plans and reduce adverse events. Lastly, embracing innovation and collaboration can improve the standard of care in chronic pain management by striking a balance between pain relief and patient safety.info:eu-repo/semantics/publishedVersio

Systemic transport of Alfalfa mosaic virus can be mediated by the movement proteins of several viruses assigned to five genera of the 30K family

We previously showed that the movement protein (MP) gene of Alfalfa mosaic virus (AMV) is functionally exchangeable for the cell-to-cell transport of the corresponding genes of Tobacco mosaic virus (TMV), Brome mosaic virus, Prunus necrotic ringspot virus, Cucumber mosaic virus and Cowpea mosaic virus. We have analysed the capacity of the heterologous MPs to systemically transport the corresponding chimeric AMV genome. All MPs were competent in systemic transport but required the fusion at their C terminus of the coat protein-interacting C-terminal 44 aa (A44) of the AMV MP. Except for the TMV MP, the presence of the hybrid virus in upper leaves correlated with the capacity to move locally. These results suggest that all the MPs assigned to the 30K superfamily should be exchangeable not only for local virus movement but also for systemic transport when the A44 fragment is present.We thank L. Corachan for her excellent technical assistance. This work was supported by the Spanish granting agency DGICYT via grant BIO2011-25018 and by the Generalitat Valenciana via grant PROMETEO 2011-003.Fajardo, TVM.; Peiró Morell, A.; Pallás Benet, V.; Sanchez Navarro, JA. (2013). Systemic transport of Alfalfa mosaic virus can be mediated by the movement proteins of several viruses assigned to five genera of the 30K family. Journal of General Virology. 94:677-681. https://doi.org/10.1099/vir.0.048793-0S6776819

Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T-786C, G894T, and INTRON variable number of the tandem repeat functional interaction

[EN] Background: Cardiovascular disease induces erectile dysfunction modulated by endothelial nitric oxide synthase enzyme and an impaired ejection fraction that restricts penis vascular congestion. However, the mechanisms regulating endothelial dysfunction are not understood. Objectives: Exploring the functional impact of endothelial nitric oxide synthase genetic polymorphisms on erectile dysfunction and drug therapy optimization in high-risk cardiovascular disease patients. Materials and methods: Patients with erectile dysfunction symptoms and candidates for andrology therapy were included (n = 112). Clinical data and endothelial nitric oxide synthase rs1799983 (G894T) and rs2070744 (T-786C), genotyped by fluorescence polarization assays, were registered. The 27-bp variable number of the tandem repeat polymorphism in intron 4 (intron4b/a) was analyzed by polymerase chain reaction-restriction fragment length polymorphism. Association analyses were run with the R-3.2.0 software. Results: A significant association between endothelial nitric oxide synthase 786-TT (p = 0.005) and the aa/ac of intron 4 variable number of the tandem repeat (p = 0.02) with higher erectile dysfunction susceptibility was observed in cardiovascular disease patients (60 +/- 9 years, 66% severe erectile dysfunction, 56% ejection fraction). After 3-months of phosphodiesterase type 5 inhibitors, erectile dysfunction (International Index of Erectile Function, 50 +/- 16 scores, the International Index of Erectile Function-Erectile Function 21 +/- 10 scores, p < 0.001) and sexual quality of life (modified Sexual Life Quality Questionnaire 55 +/- 23 scores, p < 0.001) had significantly improved. The cardiovascular ejection fraction was influenced positively with better sexual quality of life (0.1941), and also in the endothelial nitric oxide synthase G894-T allele (p = 0.076) carriers, which could merit future analyses. Erectile dysfunction was present as the primary clinical manifestation in 62% of cases, with cardiovascular disease occurring concurrently. Only former smokers and obese subjects debuted prior to cardiovascular disease than to erectile dysfunction. Conclusions: Our study provides comprehensive insights into the functional interaction linking endothelial nitric oxide synthase gene polymorphisms, erectile function, and ejection fraction in high-risk cardiovascular disease patients. Future therapeutic strategies could target endothelial nitric oxide synthase activity by including lifestyle changes and epigenetic modulations.Segura, A.; Muriel, J.; Miró Martínez, P.; Agulló, L.; Arrarte, V.; Carracedo-Garnateo, P.; Zandonai, T.... (2024). Erectile dysfunction in cardiovascular patients: A prospective study of the eNOS gene T-786C, G894T, and INTRON variable number of the tandem repeat functional interaction. Andrology. https://doi.org/https://doi.org/10.1111/andr.1367

Opioid Monitoring in Clinical Settings: Strategies and Implications of Tailored Approaches for Therapy

This review emphasises the importance of opioid monitoring in clinical practice and advocates for a personalised approach based on pharmacogenetics. Beyond effectively managing pain, meticulous oversight is required to address concerns about side effects, specially due to opioidcrisis- related abuse and dependence. Various monitoring techniques, along with pharmacogenetic considerations, are critical for personalising treatment and optimising pain relief while reducing misuse and addiction risks. Future perspectives reveal both opportunities and challenges, with advances in analytical technologies holding promise for increasing monitoring efficiency. The integration of pharmacogenetics has the potential to transform pain management by allowing for a precise prediction of drug responses. Nevertheless, challenges such as prominent pharmacogenetic testing and guideline standardisation persist. Collaborative efforts are critical for transforming scientific advances into tangible improvements in patient care. Standardised protocols and interdisciplinary collaboration are required to ensure consistent and evidence-based opioid monitoring. Future research should look into the long-term effects of opioid therapy, as well as the impact of genetic factors on individual responses, to help guide personalised treatment plans and reduce adverse events. Lastly, embracing innovation and collaboration can improve the standard of care in chronic pain management by striking a balance between pain relief and patient safet

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

Effect of Cytochrome P450 and ABCB1 Polymorphisms on Imatinib Pharmacokinetics After Single-Dose Administration to Healthy Subjects

Background: Validated genomic biomarkers for oncological drugs are expanding to improve targeted therapies. Pharmacogenetics research focusing on the mechanisms underlying imatinib suboptimal response might help to explain the different treatment outcomes and drug safety profiles. Objective: To investigate whether polymorphisms in genes encoding cytochrome P450 (CYP) enzymes and ABCB1 transporter affect imatinib pharmacokinetic parameters.Methods: A prospective, multicenter, pharmacogenetic pilot study was performed in the context of two separate oral imatinib bioequivalence clinical trials, which included 26 healthy volunteers. DNA was extracted in order to analyze polymorphisms in genes CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5 and ABCB1. Imatinib plasma concentrations were measured by HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods using WinNonlin software. Results: Volunteers (n = 26; aged 24 ± 3 years; 69% male) presented regular pharmacokinetic imatinib data (concentration at 24 h, 436 ± 140 ng/mL and at 72 h, 40 ± 26 ng/mL; AUC0-72 32,868 ± 10,713 ng/mL⋅h; and Cmax 2074 ± 604 ng/mL). CYP2B6 516GT carriers showed a significant reduction of imatinib concentration at 24 h (23%, 391 ng/dL vs 511 ng/dL in 516GG carriers, p = 0.005) and elimination half-life (11%, 12.6 h vs 14.1 h in 516GG carriers, p = 0.041). Carriers for CYP3A4 (*22/*22, *1/*20 and *1/*22 variants) showed a reduced frequency of adverse events compared to *1/*1 carriers (0 vs 64%, p = 0.033). The other polymorphisms analyzed did not influence pharmacokinetics or drug toxicity. Conclusion: CYP2B6 G516T and CYP3A4 *20,*22 polymorphisms could influence imatinib plasma concentrations and safety profile, after single-dose administration to healthy subjects. This finding needs to be confirmed before it is implemented in clinical practice in oncological patients under treatment with imatinib