Opioid use disorder in two samples of the Lebanese population: scale validation and correlation with sleep and mood disorders.

BACKGROUND: The revised Opioid Risk Tool (ORT-OUD) is a brief, self-report scale designed to provide clinicians with a simple, validated method to screen for the risk of developing an Opioid Use Disorder (OUD) in patients without a prior history of substance abuse. This study aimed to translate and validate the Arabic version of ORT-OUD in the Lebanese population and assess its clinical validity in a sample of patients with OUD. METHODS: This cross-sectional study in the Lebanese population used several validated scales to assess the risk of OUD, including the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). Other tools evaluated chronotype and sleep and mood disturbances. Principal component analysis with Varimax rotation was applied to assess ORT-OUD construct validity. Convergent validity with the Arabic version of ASSIST was evaluated. The ORT-OUD criterion validity was then assessed in a clinical sample of patients with OUD. RESULTS: This study included 581 participants. The prevalence of the OUD risk in the Lebanese population using the ORT-OUD scale and the ASSIST-opioids scale was estimated at 14.5% and 6.54%, respectively. No items of the ORT-OUD were removed; all items converged over a solution of four factors with an eigenvalue > 1, explaining a total of 68.2% of the variance (Cronbach's alpha = 0.648). The correlation coefficients between the ORT-OUD total score and ASSIST subscales were as follows: ASSIST-opioids (r = 0.174; p = < 0.001), ASSIST-sedatives (r = 0.249; p < 0.001), and ASSIST-alcohol (r = 0.161; p = < 0.001). ORT-OUD clinical validation showed a correlation with ASSIST-opioids (r = 0.251; p = 0.093) and ASSIST-sedatives (r = 0.598; p < 0.001). Higher ORT-OUD scores were associated with a family and personal history of alcohol and substance consumption and higher insomnia and anxiety scores. CONCLUSIONS: This study is the first to validate the Arabic version of ORT-OUD in the Lebanese population, an essential step towards improving the detection and management of OUD in this population.

Knowledge, Attitude, and Practices of the General Population toward the Old-New Outbreak of Cholera in a Developing Country.

Background: In October 2022, the first case of cholera since 1993 was recorded in Lebanon. This study aimed to develop and validate a tool to explore the knowledge, attitudes, and practices (KAP) toward cholera infection and its prevention among the general population in Lebanon and identify the associated factors related to the KAP assessment to guide prevention and awareness strategies. The nation's already precarious healthcare system might become overwhelmed by the response to the cholera outbreak. Therefore, evaluating the level of cholera-related KAP among the Lebanese population is crucial since it directly affects the disease's treatment, control, and prevention. Methods: This online cross-sectional study was carried out between October and November 2022 during the cholera outbreak in Lebanon. Snowball sampling was used to recruit 448 adults living in Lebanon. Results: The suggested KAP scales had adequate structural and convergent validity and were internally consistent. The disease knowledge was inversely associated with the reluctance to receive educational information (ß = -1.58) and cigarette smoking (ß = -1.31) but positively associated with the female gender (ß = 1.74) and awareness of vaccine availability and efficacy (ß = 1.34). For attitude, healthcare professionals were less frightened than others (ß = 2.69). Better practices were related to better knowledge (ß = 0.43), while inadequate practices were associated with getting information from social media (ß = -2.47). Conclusions: This study could identify notable gaps in the knowledge, attitudes, and practices, which varied according to participant characteristics. Cholera incidence can be reduced by improved community education and training, increased access to safe water, sanitation, and hygiene amenities, and changes in behavior. These findings warrant additional actions by public health stakeholders and governmental authorities to promote better practices and curb disease transmission.

Psychometric properties of the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale.

Aim: To validate the French version of the 37-item Functional Assessment of Cancer Therapy-Cognitive Function, including the four items related to multitasking, previously excluded from the scoring algorithm. Materials & methods: A cross-sectional study was carried out among 261 cancer patients. Validity was confirmed by factor analyses using the principal component analysis technique. Results: Construct validity was demonstrated, and items loaded on subscales with adequate sample adequacy to factor analyses outcomes. Better cognitive functioning was noted with age and in working patients, whereas lower functioning was observed in metastatic patients. Conclusion: The 37-item French tool is valid and reliable; questions related to multitasking could be included in the score.

A study was carried out among 261 cancer patients to evaluate their cognitive function using the French version of a 37-item validated scale. Our results demonstrated that the tool is valid and reliable. Better cognition was noted in older patients compared with younger ones, and lower cognitive functioning was observed in patients with metastatic cancer. This newly validated tool could help clinicians assess cognition in their routine practice.

Clinical and genetic factors associated with self-reported cognitive deficits in women with breast cancer: the "CAGE-Cog" study.

BACKGROUND: Breast cancer patients undergoing chemotherapy treatment are at particular risk of experiencing acute cognitive impairment leading to daily challenges in decision-making and reduced quality of life and functional autonomy. The aim was to assess the relationship between clinical and genetic factors and cognitive function in a sample of patients with breast cancer undergoing chemotherapy. METHODS: A cross-sectional study was carried out between November 2017 and June 2019 on women (N = 112) treated for breast cancer by intravenous chemotherapy at the oncology outpatient unit of Hôtel-Dieu de France Hospital, Beirut. Patients were evaluated with the 37-item Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Other validated scales were also used to assess depression, anxiety, sleep disorders, pain, and fatigue. DNA was obtained by a buccal swab (FTA®technology) for genotyping of different genes (ABCB1, COMT, DRD2, OPRM1, CLOCK, CRY2, and PER2) using the Lightcycler®(Roche). RESULTS: The mean age of participants was 56.04 years. Multivariable analysis, taking the four FACT-Cog subscores as the dependent variables, showed that the mean cognitive score decreased with higher depression, anxiety, and insomnia scores. Patients with university education levels had better perceived cognitive abilities than those with primary education. Moreover, carrying the G allele for the OPRM1 polymorphism (c.118A > G;rs197791) was significantly associated with a better cognitive function compared to AA patients (B = 2.05; p = 0.038). CONCLUSIONS: A comprehensive oncological care plan should include a personalized assessment of all factors related to cognitive functioning in cancer patients, particularly anxiety and depression, to achieve an optimal patient outcome.

Fatigue in breast cancer patients on chemotherapy: a cross-sectional study exploring clinical, biological, and genetic factors.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most common and distressing complaints reported by cancer patients during chemotherapy considerably impacting all aspects of a patient's life (physical, psychosocial, professional, and socioeconomic). The aim of this study was to assess the severity of cancer-related fatigue in a group of breast cancer patients undergoing chemotherapy and explore the association between fatigue scores and sociodemographic, clinical, biological, psychiatric, and genetic factors. METHODS: A cross-sectional pilot study carried out at the oncology outpatient unit of Hôtel-Dieu de France University Hospital recruited 67 breast cancer patients undergoing chemotherapy between November 2017 and June 2019 to evaluate fatigue using the EORTC QLQ-C30 scale (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire). Genotyping for seven gene polymorphisms (COMT, DRD2, OPRM1, CLOCK, PER2, CRY2, ABCB1) was performed using the Lightcycler® (Roche). RESULTS: The prevalence of fatigue was 46.3%. Multivariable analysis taking the fatigue score as the dependent variable showed that a higher number of cycles and a lower hemoglobin level were significantly associated with higher odds of exhibiting fatigue. Moreover, having at least one C allele for DRD2 SNP (vs. TT) was significantly associated with a 4.09 higher odds of expressing fatigue compared to TT patients. Finally, patients with at least one C allele for CLOCK SNP tended to display higher fatigue levels than TT patients. CONCLUSIONS: Our study showed that anemic breast cancer patients with a high number of chemotherapy cycles and those carrying at least one C allele for DRD2 and CLOCK SNPs are at greater risk of exhibiting fatigue. Since no previous research has reported such genetic results, future studies are necessary to confirm our findings.

Clinical and genetic factors associated with anxiety and depression in breast cancer patients: a cross-sectional study.

BACKGROUND: Despite the progress in assessment and treatment of breast cancer, being diagnosed with it or receiving chemotherapy treatment is still conceived as a traumatic experience. Women develop negative thoughts about life and death with detrimental effects on their daily physical functioning/activities, emotional state and overall quality of life. The aim of our study was to evaluate the level of anxiety and depression among breast cancer patients receiving chemotherapy and explore the correlation between these psychological disorders, clinical, sociodemographic and genetic factors. METHODS: A cross-sectional study was conducted among breast cancer patients undergoing intravenous chemotherapy at the oncology outpatient unit of Hôtel-Dieu de France hospital (November 2017-June 2019; Ethical approval number: CEHDF1016). All patients gave their written informed consent and completed several validated scales, including the Hospital Anxiety and Depression scale (HADS) for the assessment of anxiety and depression. Sleep quality, insomnia, cognitive function, fatigue and pain were also evaluated. Genotyping for certain gene polymorphisms (CLOCK, PER2, CRY2, OPRM1, ABCB1, COMT, DRD2) was performed using the Lightcycler® (Roche). RESULTS: A total of 112 women was included. The prevalence of depression was 43.4%, and 56.2% of the patients reported anxiety (based on the HADS classification). Multivariable analysis showed that higher cognitive scores and taking fosaprepitant were significantly associated with lower depression and anxiety scores. Moreover, being married compared to single was also associated with lower depression scores, whereas higher PSQI scores (worse sleep quality) and having the PER2 AA variant genotype compared to GG were significantly associated with higher depression scores. Finally, reporting a more severe insomnia and having the COMT Met/Met genotype were significantly associated with a higher anxiety score. CONCLUSIONS: Our study demonstrated a strong relationship between depression scores and cognitive impairment, sleep quality, marital status, fosaprepitant intake, and PER2 polymorphism, while anxiety scores were correlated to cognitive impairment, insomnia severity, fosaprepitant intake, and COMT polymorphism. The association with PER polymorphism was not previously reported. Identification of genetic and clinical risk factors for anxiety and depression would help clinicians implement an individualized management therapy aiming at preventing and alleviating the burden of these symptoms in breast cancer patients, hence improving their overall quality of life.

Clinical and Genetic Factors Associated With the Breast Cancer-Related Sleep Disorders: The "CAGE-Sleep" Study-A Cross-Sectional Study.

CONTEXT: Despite being among the most reported concerns in breast cancer patients, sleep disturbances are still poorly assessed and managed in routine clinical practice. Correctly evaluating these symptoms and understanding the underlying clinical and genetic factors would help medical teams develop an adequate treatment strategy for each patient. OBJECTIVES: 1) To explore the severity of insomnia as well as sleep quality in a sample of Lebanese women with breast cancer undergoing chemotherapy; 2) To examine the correlation between sociodemographic, clinical, psychiatric (anxiety and depression), genetic factors, and alterations in sleep patterns. METHODS: A cross-sectional study was carried out using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) (December 2017-June 2019; Ethical reference number: CEHDF1016). All patients gave their written consent and were genotyped for several polymorphisms in CLOCK, CRY2, PER2, COMT, DRD2, OPRM1, and ABCB1 genes using Lightcycler® (Roche). RESULTS: Our sample included a total of 112 women. Almost half of the patients reported insomnia problems (with 20.5% moderate insomnia and 7.1% severe insomnia). Multivariable analyses taking the PSQI score as the dependent variable, showed that higher depression score and dyslipidemia (yes versus no) were significantly associated with higher PSQI scores (worse sleep quality), whereas having the DRD2 CT genotype versus CC and a higher chemotherapy cycle number were significantly associated with lower PSQI scores (better sleep quality). Depression was also significantly associated with higher ISI scores. When forcing all the genes in each model, the results remained the same except for depression that has been replaced by anxiety in the multivariable analysis. CONCLUSION: Our study confirms the relationship between anxiety/depression, cycle number, dyslipidemia and DRD2 polymorphism with insomnia and highlights the importance of treating all associated factors to improve the overall QOL of patients.

Comparing cigarette smoking knowledge and attitudes among smokers and non-smokers.

Smoking prevalence in Lebanon was reported by the World Health Organization to be 43%, which is among the highest rates in the Arab nation. The objectives of this study were to assess cigarette smoking knowledge and attitude among smokers and non-smokers using validated scales in the Lebanese general population and evaluate their association with current cigarette smoking; a secondary objective is to assess the dose effect relationship of knowledge and attitude with cumulative smoking. This cross-sectional took place between May and December 2018, and enrolled a sample of 2623 participants, representative from all Lebanese governorates. A questionnaire about knowledge of the harmful effects of tobacco and attitude toward smoking bans retrieved from other studies was used to collect data. Male gender (ORa = 0.75), having a low monthly income (ORa = 1.56) and a higher passive smoking score (ORa = 1.25), were significantly associated with higher odds of being current smokers. Higher knowledge score (ORa = 0.97) and positive attitude toward smoking ban score (ORa = 0.94) were significantly associated with lower odds of being current smokers. In addition, increased age (ß = 15.21) and higher passive smoking score (ß = 26.58) were significantly associated with higher cumulative cigarette smoking. More positive attitude toward smoking ban score (ß = - 6.51) and having a university degree (ß = - 68.35) were significantly associated with lower cumulative cigarette smoking. Higher knowledge about the smoking-related health problems and better attitudes toward smoking ban were observed among non-smokers compared to smokers. It is important to increase awareness campaigns and to propose effective interventions to put in place an adequate culture of smoking cessation among the general population.

Knowledge, attitudes, harm perception, and practice related to waterpipe smoking in Lebanon.

Waterpipe smoking (WPS) is one of the most emerging popular trends in Lebanon, with a prevalence of 36.9%, the highest among all Middle Eastern countries. Thus, the primary objective of the study was to examine the factors associated with knowledge, attitudes, and practice (KAP) related to WPS among a representative sample of waterpipe smokers. The secondary objective was to examine the effect of KAP on cumulative waterpipe dose and dependence. This cross-sectional study was carried out between May and December 2018 and enrolled a representative sample of 1550 waterpipe smokers from all Lebanese districts. The questionnaire used was specifically designed for this study. High knowledge score (Beta = 0.02, p = 0.002) were significantly associated with higher waterpipe harm perception score. In addition, high knowledge score (Beta = 0.32, p = 0.007) were significantly associated with higher attitude score toward smoking ban. Higher waterpipe harm perception score (Beta = - 1.30, p < 0.001), higher attitude (Beta = - 0.21, p < 0.001), and higher knowledge score (Beta = - 0.11, p < 0.001) were significantly associated with lower waterpipe dependence. In addition, higher waterpipe dependence (Beta = 2.02, p < 0.001) was significantly associated with higher cumulative waterpipe smoking, while higher waterpipe harm perception score (Beta = - 1.96, p = 0.009) and higher knowledge score (Beta = 0.27, p < 0.001) were significantly associated with lower cumulative waterpipe smoking. Our main finding was that better knowledge and perception of the harmful effects of waterpipe were related to a better attitude toward smoking bans and a lower waterpipe smoking. Therefore, health care providers and policymakers should join efforts to make awareness campaigns across Lebanon and develop adequate interventions to curb the use of waterpipe among the population.

Association Between Adherence to Statins, Illness Perception, Treatment Satisfaction, and Quality of Life among Lebanese patients.

OBJECTIVES: The main objective of this study was to evaluate treatment adherence to statin and health-related quality of life (QOL) in Lebanese patients with dyslipidemia. Secondary objectives were to examine associations between treatment adherence, QOL, treatment satisfaction, and illness perception. METHODS: This cross-sectional study, conducted in 20 community pharmacies from all districts of Lebanon between August 2016 and April 2017, enrolled 247 adult patients taking any statin. RESULTS: The mean age of the participants was 52.63 ± 11.92 years (57.5% males); the mean duration of treatment with a statin was 59.72 months. A significant association was found between adherence and marital status ( P < .0001), educational level ( P = .001), cigarette smoking ( P < .0001), and alcohol drinking ( P < .0001). A negative but significant correlation was found between the adherence score and the duration of dyslipidemia ( r = -0.199). A significant but negative correlation was also found between the side effect score and age ( r = -0.137). The monthly salary, the marital status, the educational level, smoking cigarettes or waterpipes, and drinking alcohol were all associated with the Illness Perception Questionnaire scores ( P < 0.0001 for all variables). Secondary level of education (ß = 13.43), smoking more than 3 waterpipes per week (ß = 14.06), global satisfaction score (ß = 0.32), convenience score (ß = 0.29), and effectiveness score (ß = 0.27) would significantly increase the adherence score. Smoking more than 15 cigarettes per day (ß = -11.15) and a divorced status (ß = -14.81) would however significantly decrease the adherence score. Significant associations were found between the illness perception score, the QOL domains, and the satisfaction domains ( P < .05 for all variables). CONCLUSION: This study showed that global satisfaction with treatment, convenience, and effectiveness are important factors that increase treatment adherence. Patient adherence results in patient satisfaction and improved QOL and is an important criterion for achieving desired therapeutic outcomes.

Evaluating the impact of spirituality on the quality of life, anxiety, and depression among patients with cancer: an observational transversal study.

OBJECTIVE: Spiritual well-being was found to have some protective effect against end-of life despair in cancer patients. We aimed at assessing the impact of spirituality on the quality of life, depression, and anxiety of Lebanese cancer patients. METHODS: Our observational transversal monocentric study was conducted between January and April 2016 among a convenient sample of 115 Lebanese cancer patients admitted to Hôtel-Dieu de France Hospital (HDF), Beirut-Lebanon. In addition to socio-demographic and clinical data, three questionnaires were used: EORTC QLQ-C30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, 3rd version), FACIT-Sp-12 (Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being; The 12-item Spiritual Well-Being Scale, 4th version), and HADS (Hospital Anxiety and Depression Scale). Eighteen patients taking anxiolytic and/or antidepressants were not included in the analysis. The remaining 97 patients were analyzed. RESULTS: Better emotional and cognitive functioning was seen in patients with higher meaning, peace, faith, and total FACIT scores. Meaning, peace, and total FACIT scores were also higher among patients with better global health status and quality of life. Anxiety as well as depression was significantly associated to all spiritual well-being factors. CONCLUSION: Spirituality can improve quality of life and decrease the incidence of anxiety and depression in cancer patients. Our results highlight the need to incorporate spiritual care in healthcare systems.

Associations between quality of life, physical activity, worry, depression and insomnia: A cross-sectional designed study in healthy pregnant women.

Health-related quality of life (QOL) is reported to be reduced during pregnancy. Associations between QOL, physical activity (PA), insomnia, depression and worry are insufficiently investigated among pregnant women. The aim of this study was to evaluate QOL and PA patterns among healthy pregnant women, and to examine how QOL might correlate to PA, sleep, worry and depression. This is an observational cross-sectional study, conducted among a convenient sample of 141 healthy pregnant women using five questionnaires: WHOQOL-brief (WHO quality of life questionnaire, brief version, ISI (Insomnia Severity Index), PSWQ (Penn State Worry Questionnaire), ZSRDS (Zung Self-Rating Depression Scale), and Pregnancy Physical Activity Questionnaire (PPAQ). Pre-gestational BMI was inversely correlated to overall health while education was positively correlated to psychological health, social relationships and environment domains. Smoking before and during pregnancy significantly impacted the general health and psychological health. Total and light PA were positively correlated to psychological health and social relationships. Sports/exercise showed positive correlations with several QOL domains. Insomnia and depression were significantly associated with a decrease in all domains of QOL, while worries were associated with a decrease in physical, psychological and environmental domains. There were significant negative correlations between ZSRDS scores and total activity. PA, worries, depression and insomnia affected QOL during pregnancy. Furthermore, pregnant women presenting depression had a reduced total PA. Sleep and mental health as well as encouraging PA during pregnancy are necessary to improve the quality of life of pregnant women.

OPRM1 c.118A>G Polymorphism and Duration of Morphine Treatment Associated with Morphine Doses and Quality-of-Life in Palliative Cancer Pain Settings.

Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0.043, 0.029, and <0.001, respectively). The mean doses of morphine decreased with age but increased with the duration of morphine treatment. In addition, patients with AG genotype c.118A>G OPRM1 needed a higher dose of morphine than AA patients. Moreover, metastases, OPRM1 SNP, age, and gender were significantly associated with the QOL in our population. In particular, AA patients for OPRM1 SNP had significantly lower cognitive function than AG patients, a result not previously reported in the literature. These findings could help increase the effectiveness of morphine treatment and enhance the QOL of patients in regards to personalized medicine.

Lethal hepatotoxicity following 5-fluorouracil/cisplatin chemotherapy: a relevant case report.

Some articles have reported severe toxicities induced by cisplatin/5-fluorouracil regimens, nevertheless, severe and lethal liver toxicity has not been previously reported. In this article, we report the case of a 72-year-old woman, who developed fulminant hepatitis, hypoglycemia and hypotension with atrial fibrillation not responding to treatment. After ruling out all other possible causes of hepatitis, the toxicity was more likely attributed to 5-fluorouracil. Genotyping was performed and the patient was found to be a homozygote carrier of the T variant of the MTHFR gene. The patient died two days later. Several factors, including genetic factors, could explain this severe toxicity. The present case discusses the importance of personalized medicine in oncology based on pharmacogenetic analysis of polymorphisms.

Comparative Assessment of Off-label and Unlicensed Drug Prescriptions in Children: FDA Versus ANSM Guidelines.

PURPOSE: The main objectives of this study were to assess the incidence of off-label (OL) and/or unlicensed (UL) prescriptions in a sample of pediatric Lebanese patients by using US Food and Drug Administration (FDA) and the French Medical Regulatory Authority (ANSM) regulations. The goal was to analyze the divergences between regulations and to identify those drugs most commonly involved in OL-UL utilization. METHODS: This study was a retrospective analysis (500 pediatric files) conducted in a Lebanese University hospital in 3 pediatric wards (chronic diseases, acute diseases, and the pediatric intensive care unit). FINDINGS: The frequency of OL-UL drug use was significantly different between pediatric wards (P < 0.001), with the highest incidence occurring in the intensive care unit. The most frequent OL-UL prescriptions occurred with cancer (oncology) admissions. Age was significantly related to OL-UL frequency (highest incidence in children aged between 0 and 1 year). The number of drugs prescribed per patient ranged between 1 and 20 (mean [SD], 4.13 [2.6]). The incidence of OL-UL prescriptions was significantly higher in patients treated with a greater number of medicines (P < 0.001). Overall, 58.9% of drug prescriptions were authorized according to ANSM and 50.7% according to FDA regulations; 11.1% (ANSM) and 15.8% (FDA) were UL, and 30.2% (ANSM) and 33.5% (FDA), respectively, were OL use (where OL for the indication were the most common). The highest percentage of OL-UL prescriptions was seen with the following groups: blood and blood-forming organs, genitourinary system, and sex hormones. Divergence between FDA and ANSM was mainly observed for OL medicines. UL prescriptions assessed according to both regulations showed similar results. IMPLICATIONS: This study highlights the need for prescribers to continuously examine updates to official regulations to avoid using an OL-UL drug whenever possible. It also calls for better harmonization between worldwide official guidelines concerning drugs used in children to reduce risk factors for adverse drug reactions.

Genotyping test with clinical factors: better management of acute postoperative pain?

Individualization of acute postoperative pain treatment on an evidence-based decision process is a major health concern. The aim of this study is to investigate the influence of genetic and non-genetic factors on the variability of response to morphine in acute postoperative pain. A group of nighty-five patients undergoing major surgery were included prospectively. At 24 h, a logistic regression model was carried out to determine the factors associated with morphine doses given by a Patient Controlled Analgesia device. The dose of morphine was associated with age (p = 0.011), patient weight (p = 0.025) and the duration of operation (p = 0.030). This dose decreased with patient's age and duration of operation and increased with patient's weight. OPRM1 and ABCB1 polymorphisms were significantly associated with administered dose of morphine (p = 0.038 and 0.012 respectively). Patients with at least one G allele for c.118A>G OPRM1 polymorphism (AG/GG) needed 4 times the dose of morphine of AA patients. Additionally, patients with ABCB1 CT and CC genotypes for c.3435C>T polymorphism were 5.6 to 7.1 times more prone to receive higher dose of morphine than TT patients. Our preliminary results support the evidence that OPRM1/ABCB1 genotypes along with age, weight and duration of operation have an impact on morphine consumption for acute postoperative pain treatment.

KCNH2 polymorphism and methadone dosage interact to enhance QT duration.

BACKGROUND: Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels' genes could explain some of the "idiosyncratic" QT prolongations observed in patients treated with methadone, we tested the association between KCNE1, KCNE2, and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve. METHODS: A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1, KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed. RESULTS: The mean QTc interval was 415±34ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2, the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4ms longer QTc (95% CI [4.6-26.2]; p=0.001). CONCLUSION: KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment.

Sensory impairment in obese patients? Sensitivity and pain detection thresholds for electrical stimulation after surgery-induced weight loss, and comparison with a nonobese population.

INTRODUCTION: Obese patients have a high prevalence of painful musculoskeletal disorders that may decrease after massive weight loss. Pain thresholds may be different in obese participants. OBJECTIVES: To assess the sensitivity and pain detection thresholds, through the application of an electrical sensitivity, before and after massive weight loss, and to compare the thresholds obtained with those in a control population. METHODS: The sensitivity and pain detection thresholds obtained in participants subjected to electrical stimulation were determined in 31 obese individuals (age: 40.3 ± 10.5 y) before (body mass index: 45.7 ± 6.8 kg/m) and 6 months after a mean weight loss of 32 kg induced by gastric bypass. The results obtained were compared with those for 49 nonobese control participants (38.5 ± 11.2 y; body mass index: 22.6 ± 2.6 kg/m). Body composition and metabolic biomarkers, such as leptin, adiponectin, insulin, and interleukin 6, were assessed and single-nucleotide polymorphisms of the mu opioid receptor [OPRM1 (c.118A > G) and COMT (p.Val158Met)] were genotyped in obese patients. RESULTS: Sensitivity and pain detection thresholds (3.9 ± 1.1; 11.6 ± 6.0) were significantly higher in obese than in nonobese participants (3.1 ± 1.1; 6.0 ± 3.0), respectively (P < 0.0001), and were not affected by drastic weight loss (mean change: 32 kg). Pain thresholds in obese participants were not correlated with any of the clinical and biological variables studied. The obese participants in the highest quartile for both sensitivity and pain detection thresholds were significantly older than those in the lowest quartile. CONCLUSIONS: Further studies are required to explore sensory dysfunction in obese individuals and to investigate the implications of this dysfunction for pain management.

Pilot study examining the frequency of several gene polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in a morbidly obese population.

Morbidly obese patients are at significantly elevated risk of postsurgery complications and merit closer monitoring by health care professionals after bariatric surgery. It is now recognized that genetic factors influence individual patient's response to drug used in anesthesia and analgesia. Among the many drug administered by anesthetists, we focused in this pilot study on morphine, since morphine patient-controlled anesthesia in obese patients undergoing gastric bypass surgery is frequently prescribed. We examined the allelic frequency of three polymorphisms involved in morphine pharmacodynamics and pharmacokinetics in patients with body mass index (BMI) >40. One hundred and nine morbidly obese patients (BMI = 49.1 ± 7.7 kg/m²) were genotyped for three polymorphisms c.A118G of mu opioid receptor (OPRM1), c.C3435T of the P-glycoprotein gene (ABCB1), and p.Val158Met of catechol-O-methyltransferase gene (COMT). Allelic frequencies were 118G-0.22, C3435-0.55, and 158Met-0.5 in our whole population and 0.23, 0.5, and 0.47 in Caucasian population. Allelic frequencies did not differ according to gender. Mean BMI did no differ according to the allelic variant. OPRM1118G allele was more frequent in our population than in most previously described European populations. Since the concept of "personalized medicine" promises to individualize therapeutics and optimize medical treatment in term of efficacy and safety, especially when prescribing drugs with a narrow therapeutic index such as morphine, further clinical studies examining the clinical consequences of the OPRM1 c.A118G polymorphism in patients undergoing gastric bypass surgery are needed.