Methadone Research Articles

Cloridrato de dexmedetomidina como medicação pré- anestésica ou sedativo em cães

Relata-se, dois casos, sendo que no primeiro, realizou-se cirurgia de OVH eletiva. Como MPA,utilizou-se 2,5 mcg/kg de cloridrato de dexmedetomidina e 0,2 mg/kg de cloridrato de metadonaIM. A recuperação anestésica foi tranquila e sem complicações e o animal foi extubado apóscinco minutos, recebendo alta do centro cirúrgico 30 minutos depois. No segundo caso,realizou-se cirurgia de sepultamento da glândula da terceira pálpebra. Como sedativo, utilizouse 3,5 mcg/kg de cloridrato de dexmedetomidina e, como analgésico, 0,2 mg/kg de cloridratode metadona IM. Ao término do procedimento cirúrgico, administrou-se 0,4 mcg/kg decloridrato de atipamezole IM. Decorridos 15 minutos o paciente recuperou-se completamente,podendo ser encaminhado para alta cirúrgica. Os dois procedimentos transcorreram comvalores de PAS e bradicardia elevados,efeitos característicos do uso da dexmedetomidina. Noprimeiro caso a PAS se manteve entre 150 e 180 mmHg, no segundo, entre 160 e 180 mmHg.A partir dos casos relatados, conclui-se que o emprego da dexmedetomidina foi benéfico,proporcionando adequada medicação pré-anestésica e sedação nos referidos pacientes.

Methadone and Dignity: Advanced Medicine for the End of Life.

Methadone and Dignity: Advanced Medicine for the End of Life.

Treatment of opioid dependence with buprenorphine: current update

Opioid maintenance treatment is the first-line approach in opioid dependence. Both the full opioid agonist methadone (MET) and the partial agonist buprenorphine (BUP) are licensed for the treatment of opioid dependence. BUP differs significantly from MET in its pharmacology, side effects, and safety issues. For example, the risk of respiratory depression is lower than with MET. The risk of diversion and injection of BUP have been reduced by also making it available as a tablet containing the opioid antagonist naloxone. This review summarizes the clinical effects of BUP and examines possible factors that can support decisions regarding the use of BUP or MET in opioid-dependent people.

Estimation of Intravenous Drug Users' Population in Kermanshah City, West of Iran in 2016 using Capture-recapture Method.

Drug abuse, particularly intravenous drug use, is one of the most common challenges in human communities so that its negative impact on economic and cultural conditions of society and physical as well as mental health of individuals is evident. We aimed to estimate the IDUs' population in Kermanshah City, West of Iran using Capture-recapture method. A Cross-sectional study. The data in this study were collected from three different sources: Drop in Centers (DICs), Out Reach Teams (ORTs) and Methadone Maintenance Treatment centers (MMTs) in Kermanshah City from Mar 2015 until Mar 2016, and then indirect Capture-recapture was used to estimate the IDUs' population. The number of IDUs registered in DICs, ORTs, and MMTs were 694, 731, and 156 cases, respectively. Having determined the commonalities and removing duplicates, the number of drug users registered were 1,375 cases, after analysis of data, the number of drug users not registered in any center was estimated as 2,042 (95% CI: 1708, 2444). By counting 1,375 cases recorded in these sources, the total number of injection drug users in the Kermanshah City was about 3,417 people, (95% CI: (3083, 3819). The prevalence of IDUs in Kermanshah City is high, which could cause severe economic and social problems in the society. To reduce the negative effects of drug use, awareness and measuring of the drug users population, seem to be necessary overtime.

Illicit drugs in Emergency Department patients injured in road traffic accidents.

Urine and blood samples from 1730 drivers involved in road accidents (July 2012 - December 2015) were analyzed for the evaluation of driving under influence of drug of abuse according to the Lombardia Region guideline. The 22.5% (95% CI 20.5 to 24.5) of urine screenings tested positive for at least one class of drugs. 10.6% (95% CI 9.2 to 12.1) of the 1730 drivers were under the influence of drug, being blood concentration above the cut-off limit for at least one active substance; the proportion of illicit drugs in blood was cocaine 5.7 % (95% CI 4.7 to 6.9), cannabinoids 3.7 % (95% CI 2.9 to 4.7), opiates 1.4% (95% CI 0.9 to 2.1), methadone 1.4% (95% CI 0.9 to 2.1), amphetamines 0.2% (95% CI 0.04 to 0.5). Trend in proportion showed similar percentage (about 5%) of cocaine and cannabinoids consumption in the last two years. Poly-drug of abuse consumption emerged in the 10.4% (95% CI 6.4 to 15.7) of the positive blood and alcohol was above the legal limit in 47% (95% CI 39.6 to 54.5) of the subjects driving under the influence of drugs.

HHS secretary outrages field with methadone and buprenorphine remarks

HHS secretary outrages field with methadone and buprenorphine remarks

A possible biomarker for methadone related deaths

Methadone (MTH) concentrations in those dying of MTH toxicity totally overlap concentrations where the presence of MTH is only an incidental finding, making it very difficult to make distinctions in actual cases. A biomarker, be it anatomical or biochemical for MTH toxicity is badly needed, particularly if that markers were known to disrupt effective ventilation. Because the brainstem houses the regulatory centers for cardiorespiratory-control enters, it would seem to be the most likely anatomical site to seek abnormalities in cardiorespiratory control. ObjectiveTo locate and describe the cells of nucleus of the solitary tract (TS)(NTS) in human brainstem and determine if neuronal cell death, either necrotic or apoptotic, within the TS of humans is more common in deaths due directly to MTH toxicity than with in the solitary tract itself. Design, setting, participantsThis was a single cohort study of MTH related decedents autopsied at a large university hospital. Each decedent had a recent history of non medical/illicit MTH use and had been pronounced dead in the field, prior to ever reaching the hospital. Complete autopsy and complete toxicology testing were performed on the formalin fixed brains of each individual. Multiple blocks were prepared of the area of interest, namely the tissue lying immediately between the inferior and the super colliculi. This volume, by definition, would have included the area of the Rostral Ventrolateral Medulla (RVLM), the location of the TS. Immunohistochemistry studies utilizing caspase-9 reaction (a protease enzyme involved in the process of preprogrammed death) were performed in order to estimate the degree and proportion of neuronal apoptosis, and also access the degree of classical necrosis within the NTS. Main outcomes and measuresThe primary outcome measure was the presence or absence of neuronal apoptosis and/or necrosis within the NTS. ResultsCells displaying evidence of early apoptosis and advanced apoptosis, consisting primarily of nuclear fragmentation, admixed with other neurons displaying the features of classic necrosis were found. Evidence of classic necrosis was identifiable in most of the controls, though minor degrees of apoptosis were identifiable with Caspase staining and quantitative image analysis of immunohistochemical stains. Conclusionsand Relevance: Our study shows that neurons, primarily along the TS, but occasionally in other cell nuclei (even controls) are vulnerable, both to direct MTH toxicity (via apoptosis) and indirectly (via hypoxia leading to classical cell necrosis). When MTH is found to be present in significant concentrations, but apoptotic lesions are absent, it would be reasonable to assume that MTH was not primarily the cause of cardiorespiratory arrest.

Impact of Fentanyl Use on Maintenance Therapy During Pregnancy [40O

INTRODUCTION: Little is known about the impact of fentanyl abuse on pregnancy care. We sought to investigate whether there is a difference in the pattern of opioid maintenance requirement among pregnant women who test positive for fentanyl at their initial titration compared to those who test negative. METHODS: We conducted a retrospective cohort review of pregnant patients admitted for initial buprenorphine (STX) or methadone (MTD) maintenance dosing from April 2015 to December 2015. Demographic characteristics and obstetrics outcomes in the fentanyl positive and fentanyl negative cohorts were compared using a student’s t-test or chi square as appropriate. We compared mean MTD or STX dose required among fentanyl positive compared to fentanyl negative patients using a student’s t-test. The small sample size allowed analysis only of crude data. RESULTS: Sixteen pregnant patients were admitted for initial STX or MTD maintenance titration. Seven of these patients (43.7%) tested positive for fentanyl on admission. There were no differences in baseline demographics or obstetric outcomes in the two cohorts. There was not a significant differences in dose requirement for fentanyl positive versus fentanyl negative patients (MTD: 45 mg vs 47 mg, p=0.68; 9mg vs 10 mg STX: p=0.12). Average maintenance dos at delivery was higher for fentanyl abusers on MTD maintenance compared to fentanyl non-abusers (90 mg vs 55 mg, p=0.04). CONCLUSION: There was no significant difference in MTD or STX requirement at initial titration, but the fentanyl positive cohort maintained on MTD did require a significantly higher dose by delivery.

A correlation analysis on depression and anxiety and peripheral blood cell counts in heroin-dependent patients receiving methadone maintenance treatment

Objective To explore the relationship between depression and anxiety and peripheral blood cell counts (white blood cell (WBC), neutrophil (NEU), lymphocyte (LYM), red blood cell (RBC) and hemoglobin (HGB)) of heroin-dependent patients receiving methadone maintenance treatment (MMT). Methods Two hundred and fifty-two MMT heroin addicts, who had received peripheral blood tests within the week prior to the study, were administered with a general information questionnaire, SDS and SAS. The results of blood tests of these patients were compared with those of 109 healthy people in physical examination. Multiple linear regression was used to analyze associations between indicators of peripheral blood cell counts and depressive and anxiety symptoms. Results Compared with healthy controls, MMT patients had significantly higher proportions of elevated WBC(14.7% vs 3.7%), NEU(12.7% vs 2.8%) and LYM(9.9% vs 2.8%) counts (all P<0.05), and low RBC(10.3% vs 4.6%) counts and HGB(11.5% vs 4.6%) concentration (both P<0.05). Multivariate linear regression analysis showed that blood cell counts of WBC (β=0.261, P<0.01), NEU (β=0.264, P<0.01), LYM (β=0.196, P=0.003) and RBC (β=-0.144, P=0.021) were independently associated with depression; and blood cell counts of WBC (β=0.298, P<0.01) and LYM (β=0.269, P<0.01) were independently associated with anxiety. Conclusion Improving the inflammatory and malnutrition status may be helpful for reducing depressive and anxiety symptoms of MMT heroin addicts. Key words: Methadone maintenance treatment; Heroin dependence; Blood cell count; Depression; Anxiety

A single-nucleotide polymorphism of GRIN1 in heroin and methamphetamine addicts at a rehabilitation sanatorium in Markazi province, Iran

Introduction: Using addictive drugs can change the amount of neurotransmitters, especially dopamine and glutamate. Glutamate has been known to trigger the relapse and tendency toward addictive drugs. The glutamate receptor ionotropic NMDA type subunit 1 (GRIN1) contains the single- nucleotide polymorphism C1001G (rs11146020) and encodes N-methyl-D-aspartic acid (NDMA) receptor subunit 1 (NR1). The present study was conducted to investigate the relationship between the rs11146020 polymorphism in GRIN1 and addiction to heroin and methamphetamine. Methods: The present case-control study recruited 90 male heroin and methamphetamine addicts treated with methadone and 100 healthy men. Genomic DNA was extracted from peripheral blood using Iraizol kits. Four pairs of specific primers were designed using AlleleID 7.5, and the T-ARMS PCR was optimized. Results: The genotype distribution of GG, GC and CC was respectively found to be 66%, 31% and 3% in the control group and 58%, 31% and 11% in the patient group. The statistical analysis suggested no significant differences between these two groups. Conclusion: No significant relationships were observed between the C1001G polymorphism in GRIN1 and addiction to heroin and methamphetamine.

Risk factors of diarrhea associated with enteral nutrition in elderly patients with severe disease

Objective To study the risk factors of diarrhea associated with enteral nutrition in elderly patients with severe disease. Method One hundred elderly patients with enteral nutrition from July 2015 to May 2016 were divided into two groups. 36 elderly patients were enrolled in the diarrhea group, while 64 elderly patients without diarrhea were allocated in the control group. Body mss index (BMI) , APACHEⅡscore, whether have hypoproteinemia and mechanical ventilation, whether use antibiotics, antiacids and prokinetics, etc. Information of patients were collected, and relevant data of patients in two groups were analyzed by logistic regression. Results The multivariate logistic regression analysis showed that the most dangerous factors of enteral nutrition associated with diarrhea in patients were hypoproteinemia and mechanical ventilation during enteral nutrition (OR=2.528, 4.184; P<0.05) . Conclusions The serum protein should be assessed before carrying out enteral nutrition in elderly patients in case the presence of hypoproteinemia. For elderly patients with mechanical ventilation, the speed of enteral nutrition should slow down, the dose should be reduced with intermittent infusion. Key words: Enteral nutrition; Diarrhea; Intensive care unit (ICU); Elderly patients

Methadone and Corrected QT Prolongation in Pain and Palliative Care Patients: A Case-Control Study.

Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool. We performed a case-control study of adult inpatients receiving ME for pain management. Settings/Subjects: Adult inpatients receiving ME with a QTc >470 msec (males) and >480 msec (females) were matched 1:2 according to age, history of QTc prolongation, and gender with ME patients who did not have a prolonged QTc interval. QTc prolongation risk factors were collected for both groups. Covariates were analyzed using conditional logistic regression. Classification and regression tree analysis was used to identify the ME dose associated with QTc prolongation. Predictors of QTc prolongation included congestive heart failure (CHF) (OR: 11.9; 95% CI: 3.7-38.2; p < 0.00), peptic ulcer disease (PUD) (odds ratio [OR]: 8.3; 95% confidence interval [95% CI]: 2.4-28.9; p < 0.00), hypokalemia (OR: 6.5; 95% CI: 1.5-28.2; p < 0.01), rheumatologic diseases (OR: 4.7; 95% CI: 1.6-13.9; p < 0.00), taking medications with a known torsades de pointes (TdP) risk (OR: 4.4; 95% CI: 1.8-10.7; p < 0.01), malignancy (OR: 3.3; 95% CI: 1.2-9.3; p < 0.03), hypocalcemia (OR: 2.1; 95% CI: 0.9-4.8; p < 0.07), and ME doses >45 mg per day (OR: 1.9; 95% CI: 0.8-4.8; p < 0.16). Mild liver disease was protective against QTc prolongation (OR: 0.05; 95% CI: 0.0-0.46; p < 0.01). Predictors of QTc prolongation in our multivariate conditional logistic regression model included CHF, PUD, hypokalemia, rheumatologic disorders, use of medications with a known TdP risk, malignancy, hypocalcemia, and ME doses >45 mg per day.

Pharmacokinetics and pharmacodynamics of the injectable formulation of methadone hydrochloride and methadone in lipid nanocarriers administered orally to horses.

We investigated the thermal, electrical and mechanical antinociceptive and physiological effects (heart rate, respiratory rate, arterial blood pressure, head height and abdominal auscultation score), and pharmacokinetics, of 0.5mg/kg of the injectable formulation (ORAL) or nanoparticulated methadone (NANO) given orally, in six adult mares, using a crossover, blind and prospective design. Repeated-measure models were used to compare parametric data between and within treatments, followed by Tukey's test. Nonparametric data were analysed with Wilcoxon signed-rank, adjusted by Bonferroni tests. Blood samples were also collected up to 6h after dosing for plasma drug quantification by LC-MS/MS. Methadone pharmacokinetic parameters were determined by noncompartmental and compartmental approaches. There were no differences in pharmacodynamic parameters. No statistical differences were observed in the pharmacokinetic parameters from noncompartmental analysis for both groups, except a significant decrease in peak plasma concentration, increase in apparent volume of distribution per fraction absorbed (Vdss /F) and increased mean residence time (MRT) for NANO. One-compartment open model with first order elimination best described the pharmacokinetic profiles for both groups. Neither ORAL nor NANO administered orally to horses produced antinociception. The nanoencapsulated formulation of methadone given orally to horses did not improve methadone pharmacokinetic parameters or increased systemic body exposure to methadone.

Patients with different body mass index underwent liver enhanced CT scan: the influence of different noise indexes combined with iterative recombination algorithm on image quality and radiation dose

Objective To investigate the effect of different noise index (NI) combined with iterative recombination on the image quality and radiation dose of CT scan in patients with different body mass index (BMI). Method One hundred and sixty patients who had a liver CT enhanced scan were divided into group A (18 kg/m2 ≤ BMI< 24 kg/m2) and group B (24 kg/m2 ≤ BMI< 31 kg/m2) according to BMI, and each group had 80 patients. The two groups were randomly divided into 4 subgroups which NI value was 11, 13, 15 and 17 respectively. All images were restructured with 50% adaptive statistical iterative reconstruction. Subjective evaluation, objective evaluation [signal noise ratio (SNR) and contrast noise ratio (CNR)] and the effective dose of each group were recorded and calculated after the scan. ANOVA and Kruskal-Wallis test were used to evaluated the difference of imaging quality and radiation dose. Results In group A, the SNR, CNR and the subjective score of the later arterial phase images showed a statistical difference between NI= 17 group and other subgroups (P<0.05), while there was no statistical differences among the other three subgroups during three CT enhanced phase. The average ED of NI=15, 17 group were decreased by 57.56% (2.17/3.77) and 61.54% (2.32/3.77) compared with NI=11 group, respectively. In group B, the SNR, CNR and the subjective image scores of the later arterial phase showed a significant difference between NI=15 and NI=11, 13 group (P<0.05). There was a statistically difference of image quality in group NI=17 compared with the other three subgroups in the later arterial phase, portal venous phase and equilibrium phase (P<0.05). The average ED of NI= 13, 15 group was decreased by 26.41% (1.69/6.40) and 45.31% (2.90/6.40) compared with NI=11 group, respectively. Conclusion Upon maintaining diagnostic imaging quality, setting different NI according to BMI and applying the iterative reconstruction algorithm can effectively reduce the radiation dose of liver CT enhanced scanning. Key words: Tomography, X-ray computed; Radiation Dosage; Body weight; Noise index

Comparison of medetomidine—morphine and medetomidine—methadone for sedation, isoflurane requirement and postoperative analgesia in dogs undergoing laparoscopy

ObjectiveTo compare the effects of intravenous (IV) medetomidine-morphine and medetomidine-methadone on preoperative sedation, isoflurane requirements and postoperative analgesia in dogs undergoing laparoscopic surgery. Study designRandomized, crossover trial. AnimalsTwelve adult Beagle dogs weighing 15.1 ± 4.1 kg. MethodsDogs were administered medetomidine (2.5 μg kg−1) IV 5 minutes before either methadone (MET) or morphine (MOR) (0.3 mg kg−1) IV. Anaesthesia was induced with propofol, maintained with isoflurane in oxygen, and depth was clinically assessed and adjusted by an anaesthetist blinded to the treatment. Animals underwent laparoscopic abdominal biopsies. Sedation and nausea scores, pulse rate (PR), respiratory rate (fR), noninvasive systolic arterial blood pressure (SAP), rectal temperature (RT) and pain scores were recorded before drug administration, 5 minutes after medetomidine injection and 10 minutes after opioid administration. Propofol dose, PR, fR, SAP, oesophageal temperature (TOES), end-tidal carbon dioxide and end-tidal isoflurane concentration (Fe′Iso) were recorded intraoperatively. Pain scores, PR, fR, SAP and RT were recorded 10 minutes after extubation, every hour for 6 hours, then at 8, 18 and 24 hours. The experiment was repeated with the other drug 1 month later. ResultsNine dogs completed the study. After opioid administration and intraoperatively, PR, but not SAP, was significantly lower in MET. Fe′Iso was significantly lower in MET. Temperature decreased in both treatments. Pain scores were significantly higher in MOR at 3 hours after extubation, but not at other time points. Two dogs required rescue analgesia; one with both treatments and one in MOR. Conclusion and clinical relevanceAt the dose used, sedation produced by both drugs when combined with medetomidine was equivalent, while volatile anaesthetic requirements and PR perioperatively were lower with methadone. Postoperative analgesia was deemed to be adequate for laparoscopy with either protocol, although methadone provided better analgesia 3 hours after surgery.

Pre-emptive methadone or tramadol analgesia for mastectomy and ovariohysterectomy in bitches

Pre-emptive methadone or tramadol analgesia for mastectomy and ovariohysterectomy in bitches

Distinctive Trajectories of Opioid Use Over an Extended Follow-up of Patients in a Multisite Trial on Buprenorphine + Naloxone and Methadone.

Uncovering heterogeneities in longitudinal patterns (trajectories) of opioid use among individuals with opioid use disorder can increase our understanding of disease progression and treatment responses to improve care. The present study aims to identify distinctive opioid use trajectories and factors associated with these patterns among participants randomized to treatment with methadone (MET) or buprenorphine + naloxone (BUP). Growth mixture modeling was applied to identify distinctive opioid use trajectories among 795 opioid users after their enrollment in a multisite trial during 2006 to 2009, with follow-up interviews conducted during 2011 to 2014. Four distinctive trajectories were identified based on opioid use over the follow-up period: low use (42.0%), high use (22.3%), increasing use (17.1%), and decreasing use (18.6%). Greater odds of being in the high use group (relative to low use) was associated with Hispanics (relative to African American, odds ratio [OR] 3.21), injection drug use (OR 2.12), higher mental health functioning at baseline (OR 1.23), location on the West Coast (vs East Coast, OR 2.15), and randomization to BUP (relative to MET, OR 1.53). High use and increasing use groups had greater severity in problems related to drug, employment, legal, and social/family relationships, and worsened mental health functioning at follow-up. Participation in treatment significantly accounted for both within and between-group differences in opioid use. Continued treatment is necessary to reduce risk for opioid use and related adverse consequences, particularly among individuals (eg, injecting drug) at risk for consistently high level of opioid use.

Buprenorphine, Norbuprenorphine, R-Methadone, and S-Methadone Upregulate BCRP/ABCG2 Expression by Activating Aryl Hydrocarbon Receptor in Human Placental Trophoblasts.

Opioid dependence during pregnancy is a rising concern. Maintaining addicted pregnant women on long-acting opioid receptor agonist is the most common strategy to manage drug abuse in pregnant women. Methadone (MET) and buprenorphine (BUP) are widely prescribed for opiate maintenance therapy. Norbuprenorphine (NBUP) is the primary active metabolite of BUP. These medications can cross the placenta to the fetus, leading to postpartum neonatal abstinence syndrome. Despite their use during pregnancy, little is known about the cellular changes in the placenta brought about by these drugs. In this study, we showed that BUP, NBUP, and MET at clinically relevant plasma concentrations significantly induced BCRP mRNA up to 10-fold in human model placental JEG3 and BeWo cells and in primary human villous trophoblasts, and this induction was abrogated by CH223191, an aryl hydrocarbon receptor (AhR)-specific antagonist. These drugs increased AhR recruitment onto the AhR-response elements and significantly induced breast cancer resistance protein (BCRP) gene transcription. AhR overexpression further increased BCRP mRNA and protein expression. Knockdown of AhR by shRNA decreased BCRP expression, and this decrease was reversed by rescuing AhR expression. Finally, induction of BCRP expression in JEG3 and BeWo cells was accompanied by an increase in its efflux activity. Collectively, we have demonstrated, for the first time, that BUP, NBUP, and MET are potent AhR agonists and can induce BCRP in human placental trophoblasts by activating AhR. Given the critical role of BCRP in limiting fetal exposure to drugs and xenobiotics, long-term use of these medications may affect fetal drug exposure by altering BCRP expression in human placenta.

Diminution de la prévalence du docteur shopping de la buprénorphine entre 2004 et 2014 en France

The opioid maintenance treatments (OMT) are widely misused and diverted in many countries. Doctor shopping represented the main way to obtain high quantities of opioids in abuse/diversion. The aim of this study was to assess the trends in the prevalence of doctor shopping for high dosage buprenorphine (HDB) and methadone (MTD) from 2004to 2014by using the French Health Insurance claims. This was a cross-sectional study of patients treated by OMT (High Dosage Buprenorphine or Methadone) between 2004and 2014from a representative sample of the French Health Insurance claims. Doctor shopping was defined as at least 1day of overlapping prescriptions, written by at least 2different prescribers and filled in at least 3different pharmacies. HDB patients were more likely men (77.9% in 2014) with a mean age ranged from 33.4±7.6years in 2004to 39.5±9.3years in 2014, P<0.001. MTD patients were also more likely men (73.9% in 2014) with a mean age ranged from 33.5±6.9years in 2004to 37.1±8.5years in 2014, P<0.001. In 2014, 35% of HDB patients and 36% of MTD patients presented a long-term disease which was most frequently a mental health disorders. The prevalence of doctor shopping for HDB decreased from 2004to 2014 (12.6% versus 3.9%, P<0.001). The prevalence of doctor shopping for MTD was very low during the period study (0.2% to 0.5%). Overall, the prevalence of doctor shopping was higher for HDB than for MTD whatever the year (P<0.001) of the study. Doctor shopping for HDB decreased significantly during the last decade while doctor shopping for MTD remained nearly inexistent even if it could be underestimated because of dispensations in specialized centers and in hospitals not comprised in the insurance claims. The low rates of doctor shopping reported in these last years could result from the guidelines for good practices in OMT use made in 2004and the adjustments of ANSM (French National Agency for Medicines and Health Products Safety) for HDB best use made in 2011.

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats

ObjectiveTo determine the effects of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold in cats, following buccal and intravenous (IV) administration. Study designRandomized crossover study. AnimalsSix healthy adult female ovariohysterectomized cats weighing 4.5 ± 0.4 kg. MethodsMorphine sulfate (0.2 mg kg−1 IV or 0.5 mg kg−1 buccal), methadone hydrochloride (0.3 mg kg−1 IV or 0.75 mg kg−1 buccal), hydromorphone hydrochloride (0.1 mg kg−1 IV or 0.25 mg kg−1 buccal) or oxymorphone hydrochloride (0.1 mg kg−1 IV or 0.25 mg kg−1 buccal) were administered. All cats were administered all treatments. Skin temperature and thermal threshold were measured in duplicate prior to drug administration, and at various times up to 8 hours after drug administration. The difference between thermal threshold and skin temperature (ΔT) was analyzed. ResultsAdministration of methadone and hydromorphone IV resulted in significant increases in ΔT at 40 minutes after drug administration. Buccal administration of methadone resulted in significant increases in thermal threshold, although no significant difference from baseline measurement was detected at any time point. IV administration of morphine and oxymorphone, and buccal administration of morphine, hydromorphone and oxymorphone did not cause significant thermal antinociception. Conclusion and clinical relevanceAt the doses used in this study, IV administration of methadone and hydromorphone, and buccal administration of methadone resulted in transient thermal antinociception. The results of this study do not allow us to predict the usefulness of these drugs for providing analgesia in clinical patients.