Co-prescription network reveals social dynamics of opioid doctor shopping.

This paper examines network prominence in a co-prescription network as an indicator of opioid doctor shopping (i.e., fraudulent solicitation of opioids from multiple prescribers). Using longitudinal data from a large commercially insured population, we construct a network where a tie between patients is weighted by the number of shared opioid prescribers. Given prior research suggesting that doctor shopping may be a social process, we hypothesize that active doctor shoppers will occupy central structural positions in this network. We show that network prominence, operationalized using PageRank, is associated with more opioid prescriptions, higher predicted risk for dangerous morphine dosage, opioid overdose, and opioid use disorder, controlling for number of prescribers and other variables. Moreover, as a patient's prominence increases over time, so does their risk for these outcomes, compared to their own average level of risk. Results highlight the importance of co-prescription networks in characterizing high-risk social dynamics.

Human abuse potential studies of abuse-deterrent opioids: lessons from oral and intranasal studies with morphine abuse-deterrent, extended-release, injection-molded tablets.

BACKGROUND: The development and use of abuse-deterrent (AD) opioids is part of a multifaceted strategy to reduce misuse, abuse, and diversion, while maintaining access for patients with severe pain who may benefit from their analgesic efficacy. Morphine AD, extended-release (ER), injection-molded tablets (morphine-ADER-IMT; ARYMO ER; Egalet US Inc., Wayne, PA) is approved by the FDA as an AD opioid. As part of the characterization of AD opioids, assessments of their human abuse potential (HAP) are required. Evidence from HAP studies can guide clinicians on the use of AD opioids in clinical practice. Herein, we describe HAP study design, and how specific AD features can impact the conduct of a study and interpretation of its results. OBJECTIVES: To review the design features and results of the oral and intranasal HAP studies with morphine-ADER-IMT in order to improve the understanding of key elements of HAP studies of AD opioids. CONCLUSIONS: Results from HAP studies with morphine-ADER-IMT and other AD opioids suggest that key study design features include the release profile (immediate-release vs extended-release) of the positive control, study drug doses, and the way the products are manipulated. These elements can directly impact the outcomes of the pharmacokinetic and pharmacodynamic (e.g. Maximum Drug Liking, Overall Drug Liking, and Take Drug Again) results. When evaluating HAP studies, it is important to understand study design features to assist in the interpretation of the results and understand the clinical relevance of the data to help guide clinical decision-making about the use of AD opioids.

[Correlation between insufficient methadone dosage and morphine positive urine on drop out of treatment in patients with access to methadone maintenance treatment].

Objective: To estimate the incidence of drop out of treatment in patients with access to methadone maintenance treatment and explore the correlation and interaction between insufficient methadone dosage and morphine positive urine on the drop out in Guangxi Zhuang Autonomous Region. Methods: Face to face interview was conducted in 1 031 patients at 3 methadone maintenance treatment clinics in Guangxi. Results: The study included 1 031 participants, 40.6% of them (419/1 031) had stopped treatment. The drop out rates in urine morphine positive group and methadone dosage<100 mg/d group were 57.6% (99/172) and 37.4% (347/929) respectively, higher than those in urine morphine negative group and methadone dosage ≥100 mg/d group (42.3%, 363/859, and 26.5%, 27/102). Orderly logistic regression analysis results showed that after adjusted factors, such as gender, age, marital status, ethnic group, patients who received a dosage less than 100 mg/day (OR=3.05, 95%CI: 1.84-5.06) and had morphine positive urine (OR=2.25, 95%CI: 1.59-3.19) were more likely to drop out of the treatment. Interaction analysis showed that dosage less than 100 mg/d and morphine positive urine during treatment had additive interaction (RERI=256.46, AP=0.87, S= 8.05) and multiplication interaction (OR=2.45, 95%CI: 1.71-3.49). Conclusion: Insufficient dosage and morphine positive urine were significantly correlated with drop out of treatment in patients with access to methadone maintenance treatment.

Opioid agonist doses for oxycodone and morphine dependence: Findings from a retrospective case series.

INTRODUCTION: Use of opioid agonist treatments for prescription opioid (PO) dependence is rapidly increasing. Current guidelines are based on research with heroin users. This study aimed to examine methadone and buprenorphine dose requirements for PO-dependent people. DESIGN AND METHODS: A retrospective case series of PO-dependent patients entering methadone and buprenorphine treatment. Daily oral morphine equivalent (OME) doses at baseline were calculated using standard dose conversion calculations. Dose conversion tables were used to estimate opioid agonist doses, based on starting dose of PO. Baseline methadone and buprenorphine dose at days 7 and 28 were examined. Linear models were fit to the data. RESULTS: Participants (n = 44) were 67% male, mean age 41 years (SD 10 years); 69% reported a pain condition. The methadone group (n = 21) had a mean PO dose of 704.5 mg OME (SD 783.5 mg) prior to treatment, and mean methadone dose of 45.3 mg (SD 13.1 mg) at day 7 and 61.6 mg (SD 20.8 mg) at day 28. The buprenorphine group (n = 23) had a mean PO dose of 771.7 mg OME (SD 867.7 mg) prior to treatment, with a mean dose of 14.6 mg (SD 8.3 mg) at day 7 and 18.1 (SD 8.9 mg) at day 28. Linear relationships were not found between OME and opioid agonist dose. CONCLUSIONS: Opioid agonist dosages varied substantially between individuals, and from predicted dosages based on dose conversion tables. Use of conversion tables to guide selection of opioid agonist dosage may compromise patient safety. [Nielsen S, Bruno R, Degenhardt L, Demirkol A, Lintzeris N. Opioid agonist doses for oxycodone and morphine dependence: Findings from a retrospective case series Drug Alcohol Rev 2017;36:311-316].

Evidence of slow-release morphine sulfate abuse and diversion: epidemiological approaches in a French administrative area.

Slow-release oral morphine sulfate (SM) is one of the most abused prescription opioids in France. However, the regional feature of the abuse of morphine is poorly documented. To investigate the abuse of SM in a French administrative region, a multisource approach was applied. The first approach was based on SM exposition at national and regional level using the OPPIDUM survey. In a second approach, we analyzed a drug reimbursement database to assess the magnitude of SM abuse in Languedoc-Roussillon (LR) region. A clustering method was applied to classify patients and to describe the profile of deviant patients. The third approach was based on a self-administered anonymous questionnaire, proposed to patients seen in addiction care centers in the LR region and consuming oral SM. The OPPIDUM study showed that in most regions, where the prevalence of heroin use is higher than the national average of 9.1%, SM consumers were fewer. With the clustering method, three subgroups were identified. One of them gathered 35 users (3.2%) with a deviant behavior characterized by significantly more dispensations, dispensing pharmacies, and prescribers. These subjects were mainly men, younger, and more consumers of benzodiazepines and opioid maintenance therapy than the others. The third study allowed specifying that SM was mainly injected (93.7%), bought in the street (80%), and used because of unavailability and the poor quality of heroin (33.9%). The three proposed approaches are complementary and help to clarify the abuse of oral SM, while assessing the motivations of this abuse.

Jurisdictional differences in opioid use, other licit and illicit drug use, and harms associated with substance use among people who tamper with pharmaceutical opioids.

INTRODUCTION AND AIMS: The harms associated with non-medical use of pharmaceutical opioid analgesics are well established; however, less is known about the characteristics and drug-use patterns of the growing and hidden populations of people using pharmaceutical opioids illicitly, including the frequency of pharmaceutical opioid injection. This paper aimed to undertake a detailed examination of jurisdictional differences in patterns of opioid use among a cohort of people who regularly tamper with pharmaceutical opioids in Australia. DESIGN AND METHODS: Data were drawn from the National Opioid Medications Abuse Deterrence study. The cohort was recruited from New South Wales (NSW; n = 303), South Australia (SA; n = 150) and Tasmania (TAS; n = 153) to participate in face-to-face structured interviews collecting data on use of pharmaceutical opioids, benzodiazepines, other sedative drugs and illicit substances, as well as the harms associated with substance use. RESULTS: TAS participants reported greater use and injection of certain pharmaceutical opioids (particularly morphine and methadone tablets), and limited heroin use, with lower rates of engagement in opioid substitution treatment, compared with NSW participants. NSW participants were more socially disadvantaged and more likely to report risky injecting behaviours and injecting-related injuries and diseases compared with SA and TAS participants. SA participants reported greater rates of pain conditions, greater use of pain-based services, as well as broader use of pharmaceutical opioids in regards to forms and route of administration, compared with NSW participants. DISCUSSION AND CONCLUSIONS: Distinct jurisdictional profiles were evident for people who tamper with pharmaceutical opioids, potentially reflecting jurisdictional differences in prescribing regulatory mechanisms and addiction treatment models.

Dentition of addiction in Queensland: poor dental status and major contributing drugs.

BACKGROUND: Although it is said that drug addiction is associated with poor dental health, there is little research in this area. In particular, there is little work comparing the effects of the different drugs of addiction. METHODS: A cross-sectional patient survey of dental health was undertaken in a family practice comparing opiate and other drug addicts (DA) with non-addicts (NA). The age range was restricted to 19-45 years. Damaged teeth were counted and a semi-quantitative score applied to severity to allow the calculation of an overall dental index. A medical review only was undertaken; recognized dental diagnostic criteria were not applied. RESULTS: There were 233 and 47 respondents in the DA and NA groups, respectively. The mean ages and gender ratios were similar in both groups. DA used more addictive drugs than NA (all P < 0.001). DA had more absent, traumatized, major cavitated and extracted teeth (all P < 0.05). Addicts had a worse severity index (P < 0.02) and dental index (13.13 + 24.00 vs. 4.74 +/- 16.03; P < 0.005). Furthermore, dental pathology developed in DA at younger ages than in NA with 56.8% vs. 5.4% of patients younger than 38 years having dental indices more than 10 respectively (OR = 22.98, 95% CI = 5.57-200.65, P < 0.0000001). At multivariate analysis age, gender, and dose and/or duration of tobacco, methadone, morphine, and alcohol were significantly associated with these pathologies. CONCLUSION: These data are consistent with published dental reports and basic science information that drug addiction has a deleterious effect on dental health, that in addiction this effect is rapid and severe, and that tobacco, methadone, morphine and alcohol contribute importantly to these changes.

Patterns of drug use and associated harms among rural injecting drug users: comparisons with metropolitan injecting drug users.

OBJECTIVE: Given the harms associated with injecting drug use to both individuals and community and the paucity of such data from rural areas, the study aimed to compare: patterns of drug use, harms, and service access and utilisation among rural and metropolitan injecting drug users (IDU). DESIGN: Cross-sectional survey, using interviewer-administered structured questionnaire. PARTICIPANTS: One hundred and sixty-four rural and 96 metropolitan IDU from seven different New South Wales Area Health Services, recruited through needle and syringe programs (NSPs), snowballing techniques and advertisement. RESULTS: Age, gender, education and employment were similar for rural and metropolitan participants. Both samples reported use of a range of drugs, but rural participants were less likely than metropolitan participants to report daily heroin use (2% vs 10%), but more likely to report having injected morphine (50% vs 21%) in the last six months. Similar proportions reported using a needle/syringe after another person. Rural participants were less likely to report use of NSPs (36% vs 80%) and reported a number of barriers to NSP access and also to drug treatment services. Rural participants reported a significantly longer period of time between blood-borne virus testing. CONCLUSION: Samples of rural IDU are similar to metropolitan, although report some differences in patterns of drug use. Service provision, including access to new injecting equipment, blood-borne virus testing and drug treatment was found to cause considerable problems for rural IDU. These issues warrant further consideration.

[Current consumer conditions among opioid addicts--implications for maintenance-treatment programmes provided by ambulatory drug treatment centers and physicians]. / Aktuelle Konsumformen bei Drogenabhängigkeit--Implikationen für Substitutionsprogramme in ambulanten Einrichtungen und bei behandelnden Arzten.

BACKGROUND: Anonymous evaluation of the current conditions of drug scene and drug consumption, entrance age, personal motives for drug consumption and satisfaction among opioid-dependent clients with treatments available within an ambulant maintenance treatment setting. METHODS: The questionnaire for the study was based on representative studies and covered 112 questions regarding drug consumption. In addition, an instrument of the "Hessische Landesstelle gegen die Suchtgefahren", which measures satisfaction of opioid clients regarding public drug-treatment centers, was used. RESULTS: A total of 158 opioid clients within an ambulant maintenance treatment setting were enrolled in the study. The mean age at first drug consumption was 15.1 (2.4) years for men and 15.2 (3.5) years for women. The Spearman correlation showed a significant positive correlation (r=0.284) between age and time of first drug consumption (p=0.019). Cannabis was the most frequent entrance drug (55.8%), followed by alcohol (33.8%), opioids (17.6%) and nicotine (11.8%). Additional consumption of benzodiazepines was observed in 44.7% of men and 39.7% of women, of cannabis in 74.5% of men and 52.4% of women, and of sustained-release morphine in 41.4% of men and 33.3% of women. Within the previous 6-12 months cocaine was consumed significantly less (p=0.024) by men (63.8%) than by women (90.5%). 93.3% of the drug users rated a follow-up assistance programme after withdrawal and 71.9% special care programmes for designer drugs very important. IMPLICATIONS: The present study supports the assumption of an earlier age of first drug consumption. In view of our findings on entrance age, and on polytoxicomanic consumption patterns and gender-specific differences, we believe that the objectives of substitution programmes can only be reached if programmes are adequately adapted to the actual conditions of the drug scene and are able to cooperate with other public drug-treatment systems.

Nervous regulation of breathing in opiate dependent patient. Part II. Respiratory system efficiency and breathing regulation of persons classified to the methadone maintenance treatment.

The measurements of respiratory pattern parameters, occlusion pressure and respiratory tract resistance had never been performed in opiate dependent persons administered by the methadone maintenance treatment. The aim of this study was assessment of ventilatory efficiency and nervous regulation of 35 depended on opiates before starting the treatment. The presently examined opiate addicts classified to the methadone programme had intensified changes in nervous breathing regulation compared to the group of opiate dependent patients treated at the Department of Clinical Toxicology CMUJ in the first stage of controlled abstinence and to the control group. They had the higher values of minute ventilation, occlusion pressure and higher value of tidal volume to the inspiratory flow (VT/TIN) index which is the driving component of the breathing cycle and reflects the activity of the respiratory centres in the spinal cord and pons. A monitoring of respiratory patterns parameters, occlusion pressure and respiratory resistance, which are not disturbed or biased by lack of patient's cooperation, will allow to determinate the direction of changes in ventilatory efficiency in the course of methadone maintenance treatment programme.

[Drug abuse among new draftees]. / Rusmiddelbrug blandt nyindkaldte vaernepligtige.

The aim of the study was to investigate the pattern of the use of drugs among young conscripts by a test screening of their urine. The participants in the investigation also filled in a questionnaire about use of drugs. The urine samples from 916 young recruits were examined for cannabinoids and 429 were also examined for amphetamines, cocaine, opiates and benzodiazepines. We found 68 (7.8%) positive tests for cannabis and a negligible number of positive tests for other drugs. The questionnaire showed a lower statement of use of drugs though 3.3% stated a daily or weekly use of cannabis. Fifty-eight percent of the soldiers admitted that they had tried cannabis. Six percent had used other drugs. The consumption of alcohol is low during weekdays. We concluded that the conscripts did not constitute a population of drug abusers. We recommend that urine test screening (regular or spot test) should be incorporated in the future medical examination in the Danish Army to pinpoint personnel with a moderate use of cannabis.

The misuse of buprenorphine and a buprenorphine-naloxone combination in Wellington, New Zealand.

Two surveys of 12 months duration were undertaken on opioid users presenting to the Wellington Alcohol and Drug Centre before and after the introduction of a combination buprenorphine 0.2 mg-naloxone 0.17 mg tablet (Bu-Nx), which was launched in 1991 in the hope of reducing intravenous misuse. There was considerable intravenous (i.v.) misuse of buprenorphine 0.2 mg tablets (Bu) in 1990 with self-reports of misuse in 81% of the patients over the 4 weeks prior to presentation, and 65% of the patients had buprenorphine in their urine. In the repeat survey 57% reported misuse of the Bu-Nx combination over the previous 4 weeks, and 43% had buprenorphine +/- naloxone detected in their urine. There was a reduction in the street price of Bu-Nx. One-third of the patients who used Bu-Nx i.v. reported instances of withdrawal symptoms, and subjectively the drug was less attractive to misusers. The combination product may have less misuse potential than buprenorphine alone, but it remains a preparation, in the dosages employed, that is intravenously misused.

HIV infection among injecting drug users in north-east Malaysia, 1992.

Human immunodeficiency virus (HIV) has spread widely among injecting drug users (IDUs) in countries to the north and west of the 'Golden Triangle' region of South-East Asia; it is likely to have spread southwards to Malaysia as well. In order to assess HIV seroprevalence among IDUs in north-east Malaysia and describe risk factors for HIV infection in this population, we performed a cross-sectional seroepidemiological study among 210 IDUs recruited at the detoxification ward of the General Hospital in the capital city of the north-eastern Malaysian state, Kelantan. Subjects were sequential entrants to the detoxification ward, interviewed about HIV risk behaviour, and tested for antibody to HIV and to syphilis. Nearly a third (62/210, 30%) of these IDUs were HIV seropositive. Three-quarters (159/210) had travelled to Thailand in the preceding 5 years, of whom 32% (51/159) were HIV seropositive; this was associated with injecting in Thailand, but not with sexual contact there. Of those who had not left Malaysia in the preceding 5 years, 26% (11/43) were HIV seropositive, a rate not significantly different from those who had travelled. Travel within Malaysia was common (144/210, 69%) among IDUs interviewed, as was unsafe injecting and unsafe sexual behaviour (20% had shared injecting equipment and 21% had had unprotected intercourse) in other states. In every locale, rates of unsafe injecting behaviour were high (55% sharing in last month), even among those who knew they were HIV infected, and rates of condom usage were low (93% of 160 sexually active IDUs had never used a condom). Syphilis was not associated with HIV infection, but with contact with Thai prostitutes.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: 210 intravenous drug users (IVDU) recruited in the detoxification ward of the general hospital in the capital city of the northeastern Malaysian state of Kelantan were interviewed about their HIV risk behavior and tested for antibodies to HIV and syphilis. The study was conducted to assess HIV seroprevalence among IVDUs in northeast Malaysia and describe risk factors for HIV infection in that population. 62 of the individuals were HIV-seropositive (HIV+). 159 of the 210 had travelled to Thailand in the preceding 5 years, of whom 51 were HIV+. Their serostatus was associated with injecting in Thailand, but not with sexual contact there. Of the 43 who had not left Malaysia in the preceding 5 years, 11 were HIV+; this 26% rate is not significantly different from the rate among those who had travelled. 69% of the sample had travelled within Malaysia; 20% had shared injecting equipment; and 21% had had unprotected sexual intercourse in other states. 55% had shared injecting equipment in the previous month, even among those who knew they were infected with HIV. 93% of sexually active IVDUs had never used a condom. Syphilis was not associated with HIV infection, but with contact with Thai prostitutes. Multivariate analysis found that the major predictors of HIV seropositivity were multiple sharing partners, low income, and few years of education. These findings support the notion that HIV is widespread among IVDUs in northeast Malaysia and that it is associated with low socioeconomic status. HIV is spreading endogenously within Kelantan and probably in other states. The frequent risk behavior in this high prevalence population suggests that transmission rates will probably stay high and that large-scale prevention efforts are urgently needed.