Opioid Use Disorder: A Qualitative Exploratory Analysis of Potential Misunderstandings in Patients with Chronic Non-Cancer Pain.

Purpose: Substance use disorders (SUD) are a challenging comorbidity in patients with chronic non-cancer pain (CNCP) as they complicate diagnosis and therapy, especially when opioids are part of the therapeutic regimen. A definite diagnosis of opioid use disorder (OUD) in patients with CNCP on long-term opioid therapy (LTOT) is a prerequisite for effective and targeted therapy but may be complicated as some criteria of OUD might be attributed to the desire of the patient to relieve the pain. For instance, the desire to increase the dose can be based on both a SUD as well as inadequate pain therapy. Many scientific studies use standardized questions. Therefore, potential misunderstandings due to possible diagnostic overlaps often cannot be clarified. Methods: 14 qualitative guided interviews were conducted and analyzed (Kuckartz content analysis), with the intention to verify if patient's initial response to simple questions based on the wording of the DSM-5, as commonly used in research and practice, were consistent with the results of a more in-depth inquiry. Results: The results suggest that without in-depth investigation, there is a particular risk of false-positive assessment of the DSM-5 criteria for OUD when opioids are prescribed, especially when the questions are considered independently of chronic pain. The risk of a false-negative assessment has also been shown in isolated cases. Conclusion: Only after asking for and describing specific situations it was possible to determine whether the patient's positive or negative answers were based on a misunderstanding of the question. To avoid misdiagnosis, staff conducting DSM-5 interviews should be trained in pain-specific follow-up questions that may help to uncover diagnostic confounding.

Patient Perspectives on Pharmacotherapy of Alcohol Dependence.

INTRODUCTION: Pharmacotherapy with drugs like naltrexone or acamprosate is a well-evaluated element in the treatment of alcohol dependence (AD). However, in many countries, these medications are rarely administered. The objective of the present study was to identify from patients' perspective factors that prevent the initiation and compliance with pharmacological treatment of AD. METHODS: Patients from inpatient alcohol withdrawal treatment underwent a standardized interview. Questions included socio-demographic data, history of AD, treatment history, knowledge and personal experience regarding pharmacotherapy of AD, and personal views about the causes of AD. RESULTS: Three hundred patients (mean age 47.3 years, 27.7% female, mean duration of AD 8.9 years, 67% with a history of previous inpatient withdrawal treatment) were included. The majority of patients (58.7%) already knew drugs for the pharmacotherapy of AD. Thirty percent had ever used such medications, most often acamprosate. Except for disulfiram, pharmacotherapy of AD had lasted only a few weeks, on average. Medication usually had been applied without additional psychotherapy. No severe side effects were reported. Patients had often stopped pharmacotherapy on their own, when assuming they had reached stable abstinence. Openness to start pharmacotherapy for AD was currently stated by 67% of the total sample. In multiple logistic regression, openness was predicted by having a concept of AD as a medical disease and by a shorter duration of AD. DISCUSSION: To improve the administration of pharmacotherapy for AD implementation strategies should be systematically developed and evaluated with a focus on the concept of AD as a medical disease.

[Multimorbidity and its Importance in Future Health Care in Germany: a Secondary Data Analysis Based on 67 Million Health Insurance Policy Holders]. / Multimorbidität in Deutschland und ihre Bedeutung für die Versorgung der Zukunft ­ eine Sekundärdatenanalyse basierend auf 67 Mio. Versichertendaten.

BACKGROUND: Multimorbidity is a particular challenge for health care systems. In Germany, epidemiological findings are primarily sample-based. The estimated prevalence among adults in Germany is high, but there are methodological problems, such as a lack of a uniform definition. METHOD: Statutory health insurance data from the information system for health care data ("Informationssystem Versorgungsdaten") of the former German Institute for Medical Documentation and Information were analyzed. A total of 67.3 million people with statutory health insurance in 2014 were included. Multimorbidity was defined by the presence of at least three chronic diseases from a list of 46 diseases per ICD-10. RESULTS: A total of 21,157,937 individuals, or 31.4% of the total cohort, were defined as multimorbid. In men, progression of multimorbidity occurred at the age of about 40 years, whereas the increase was seen at the age of about 35 years in women. The different disease burden varied in different age and sex groups. CONCLUSION: A better understanding of complex disease interactions in relation to age and sex is needed. Interdisciplinary approaches with specific care concepts for multimorbidity, adapted to the chronic care model, should be explored in order to achieve an ideal care situation in Germany.

[Changes in Prescription Patterns of Oral Anticoagulants in Family Practices after Marketing Approval of Direct Oral Anticoagulants]. / Änderungen bei der Verordnung oraler Antikoagulation in Hausarztpraxen nach Einführung der direkten oralen Antikoagulanzien.

AIM OF THE STUDY: Since 2011, non-vitamin-K-dependent oral anticoagulants (NOAC) have extended the spectrum of anticoagulation therapy. Initially, the approval of NOAC was limited to the prophylaxis of postoperative thrombosis, but in the course of time the spectrum was extended to the therapy of thrombosis and embolism as well as anticoagulation in non-valvular atrial fibrillation. The study was designed to examine how the approval of NOAC had affected the prescribing behaviour of general practitioners in the first years of their approval. METHODS: In a retrospective longitudinal study, the prescriptions of anticoagulants between 2012 and 2017 were analysed in 3 general practitioners' practices in the Bonn area. The study included all patients for whom at least one prescription from a NOAC or a vitamin K antagonist (VKA) was documented in the administrative system of the practices during this period. RESULTS: A total of n=579 patient files were evaluated (47% female; median age 75 years). Of these, 47% received a VKA, and 40% a NOAC (59% rivaroxaban, 29% apixaban, 9% dabigatran and 3% edoxaban). During the period under examination, the share of VKA prescriptions decreased from 45% to 14% and the share of NOAC increased from 28% to 87%. Anti-coagulation was changed in 12%. The most frequent change was from a VKA to a NOAC (70%). CONCLUSION: After marketing approval, the use of NOAC in the initial prescriptions increased steadily. This trend can also be seen in other European studies. VKA are mainly prescribed to patients with stable oral anticoagulation. As recommended in the guidelines, anticoagulation is changed mainly when problems occur during therapy. If the trend in the prescription of anticoagulants continues, in the medium term, VKA will only be prescribed for patients who have been stable for many years and for patients with artificial heart valves.

Specialized Outpatient Palliative Care­Clinical Course and Predictors for Living at Home Until Death

BACKGROUND: Specialized outpatient palliative care (SOPC) is an important component of the palliative medicine care concept in Germany. Its purpose is to improve the out-of-hospital care of patients who cannot be adequately cared for by their primary care physicians and in the setting of general outpatient palliative care (GOPC). METHODS: In this retrospective analysis of anonymized routine treatment data, we analyzed the characteristics of SOPC patients overall and with specific diseases, and depicted them both numerically and graphically. We also carried out a regression analysis of the factors affecting whether or not patients will be able to die in a home environment. RESULTS: The analysis included data from 14 460 patients who were treated by 14 different SOPC teams in the North Rhine area of Germany in 2017 and 2018. The majority of patients who died were able to live at home until death (85.9%); only a small percentage died as inpatients (7.7%). The symptom burden shortly before death was less than at the beginning of treatment. The factors displaying a statistically significant association with dying at home were: more advanced age (aOR 0.96; 95% CI: [0.95; 0.96]), female sex (aOR 0.85; 95% CI: [0.74; 0.98]), and house calls at night (aOR 0.60; 95% CI: [0.51; 0.71]). CONCLUSION: SOPC met its declared objectives of limiting distressing symptoms and enabling patients to live at home until death.

[Critical discussion of new data regarding prevalence of opioid use disorder in patients with chronic pain in Germany]. / Kritische Auseinandersetzung mit neuen Daten zur Prävalenz von Opioidgebrauchsstörungen bei Patienten mit chronischen Schmerzen in Deutschland.

BACKGROUND: There is no opioid crisis in Germany. However, new studies involving patients with chronic noncancer pain (CNCP) in Germany show an unexpectedly high prevalence of opioid use disorder according to DSM­5 (Diagnostic and Statistical Manual for Psychiatric Diseases). OBJECTIVES: Critical discussion of new study results on the prevalence of opioid use disorder in CNCP patients in Germany. MATERIALS AND METHODS: Selective literature search and multiprofessional classification of results by an expert panel (pain therapy, neurology, psychiatry, palliative medicine, general medicine and addiction therapy). RESULTS: The DSM­5 criteria for the diagnosis of "opioid use disorder" have limited applicability to patients with CNCP, but may raise awareness of problematic behavior. The diagnosis of opioid use disorder is not the same as the diagnosis of substance dependence according to ICD-10, as the DSM­5 diagnosis covers a much broader spectrum (mild, moderate, severe). Risk factors for opioid use disorder include younger age, depressive disorders, somatoform disorders, and high daily opioid doses. The interdisciplinary guideline on long-term opioid use for CNCP (LONTS) includes recommendations intended to reduce the risk for opioid use disorder. CONCLUSION: An adaptation of the DSM­5 diagnostic criteria of opioid use disorder to the specific situation of CNCP patients and a validation of these criteria could help to collect more accurate data on opioid use disorders of patients with chronic pain in Germany in the future. Prescribers should be sensitized to this problem without pathologizing or even stigmatizing patients. Further research is needed to classify this previously underestimated phenomenon.

Individualized versus Standardized Risk Assessment in Patients at High Risk for Adverse Drug Reactions (The IDrug Randomized Controlled Trial)-Never Change a Running System?

The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. In total, N = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95%CI 1.02-2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95%CI 1.05-3.76]), and not significant on DOAC treatment (OR 1.52 [95%CI 0.63-3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance.

Factors influencing length of survival in ambulatory palliative care - a cross sectional study based on secondary data.

BACKGROUND: Quality of life and patient self-determination are key elements in successful palliative care. To achieve these goals, a robust prediction of the remaining survival time is useful as it can provide patients and their relatives with information for individual goal setting including appropriate priorities. The Aim of our study was to assess factors that influence survival after enrollment into ambulatory palliative care. METHODS: In this cross-sectional, multicenter study (n = 14 study centers) clinical records of all palliative care patients who were treated in 2017 were extracted and underwent statistical analysis. The main outcome criterion was the association of survival time with clinical characteristics such as age, type of disease, symptoms and performance status. RESULTS: A total of 6282 cases were evaluated. Median time of survival was 26 days (95 % CI: 25-27 days). The strongest association for an increased hazard ratio was found for the following characteristics: moderate/severe weakness (aHR: 1.91; 95 % CI: 1.27-2.86) Karnofsky score 10-30 (aHR: 1.80; 95 % CI: 1.67-1.95), and age > 85 (aHR: 1.50; 95 % CI: 1.37-1.64). Surprisingly, type of disease (cancer vs. non-cancer) was not associated with a change in survival time (aHR: 1.03; 95 % CI: 0.96-1.10). CONCLUSIONS: In this cross-sectional study, the most relevant predictor for a short survival time in specialized ambulatory palliative care was the performance status while type of disease was irrelevant to survival.

Correction: Rate of opioid use disorder in adults who received prescription opioid pain therapy-A secondary data analysis.

[This corrects the article DOI: 10.1371/journal.pone.0236268.].

Risk factors for a positive SARS-CoV-2 PCR in patients with common cold symptoms in a primary care setting - a retrospective analysis based on a joint documentation standard.

BACKGROUND: Combating the COVID-19 pandemic is a major challenge for health systems, citizens and policy makers worldwide. Early detection of affected patients within the large and heterogeneous group of patients with common cold symptoms is an important element of this effort, but often hindered by limited testing resources, false-negative test results and the lack of pathognomonic symptoms in COVID-19. Therefore, we aimed to identify anamnestic items with an increased/decreased odds ratio for a positive SARS-CoV-2 PCR (CovPCR) result in a primary care setting. METHODS: We performed a multi-center cross-sectional cohort study on predictive clinical characteristics for a positive CovPCR over a period of 4 weeks in primary care patients in Germany. RESULTS: In total, 374 patients in 14 primary care centers received CovPCR and were included in this analysis. The median age was 44.0 (IQR: 31.0-59.0) and a fraction of 10.7% (n = 40) tested positive for COVID-19. Patients who reported anosmia had a higher odds ratio (OR: 4.54; 95%-CI: 1.51-13.67) for a positive test result while patients with a sore throat had a lower OR (OR: 0.33; 95%-CI: 0.11-0.97). Furthermore, patients who had a first grade contact with an infected persons and showed symptoms themselves also had an increased OR for positive testing (OR: 5.16; 95% CI: 1.72-15.51). This correlation was also present when they themselves were still asymptomatic (OR: 12.55; 95% CI: 3.97-39.67). CONCLUSIONS: Several anamnestic criteria may be helpful to assess pre-test probability of COVID-19 in patients with common cold symptoms.

Rate of opioid use disorder in adults who received prescription opioid pain therapy-A secondary data analysis.

BACKGROUND AND AIMS: Data on rates of prescription opioid use disorder (pOUD) in European countries is limited. The aim of this investigation was to analyze a representative population sample regarding the 1-year prevalence of opioid use disorder in patients who received prescription opioid pain therapy and to identify related risk factors. DESIGN: Cross-sectional secondary data analysis. SETTING: Secondary data analysis based on data from the 2015 Epidemiological Survey of Substance Abuse (ESA 2015) in Germany. PARTICIPANTS: German-speaking individuals living in private households aged 18 to 64 years were investigated. A total of 9204 individuals participated in the survey, resulting in a response rate of 52.2%. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measure was the weighted prevalence of pOUD in the subgroup of study participants who had received prescription opioids. Secondary outcome measure was an analysis of risk factors connected with pOUD in the same subgroup. FINDINGS: A total of n = 9204 participants were included in the study of which n = 275 had received an opioid prescription in the last 12 months of which n = 54 were diagnosed with pOUD. The weighted 1-year prevalence of pOUD was 21.2% (mild: 14.7% | moderate: 3.5% | severe: 2.9%). Participants who had received opioid pain therapy had significantly higher odds of pOUD if they reported signs of depression (OR: 2.69; CI 95%: 1.13-6.38), inexplicable physical complaints (OR: 2.68; CI 95%: 1.14-6.31) or a psychiatric diagnosis (OR: 4.12; CI 95%: 1.36-12.43), and significantly lower odds of pOUD if they reported the use of non-opioid painkillers (OR: 0.27; CI 95%: 0.09-0.81). CONCLUSIONS: pOUD is a common phenomenon in working-age patients who receive prescription opioid pain therapy in Germany and may be related to the co-existence of psychosomatic and psychiatric disorders such as depression.

[Addressing Issues of Living Will and Power of Attorney in Patients With Dementia - A Cross-Sectional Study Among German General Practitioners]. / Hausärztlicher Umgang mit Patientenverfügung und Vorsorgevollmacht bei Demenzpatienten ­ Eine Querschnittsstudie unter deutschen Hausärzten.

OBJECTIVES: Issues of living will and power of attorney must be addressed as early as possible in dementia patients because of their decreasing independence and ability to act for themselves. The aim of this study was to investigate whether general practitioners (GPs), who usually have long-standing and regular contact with this group of patients, address these precautionary measures and if there is any association between this approach and further communication and educational behaviour of doctors. METHODS: A cross-sectional survey, using standardized, written questionnaires, was conducted in a random sample of 982 GPs in North Rhine-Westphalia in western Germany between October 2017 and January 2018. Descriptive statistical as well as logistic regression analyses were carried out using IBM SPSS Statistics, version 24. RESULTS: A total of 339 GPs responded to the survey questionnaire (response rate: 34.5%). A majority of GPs (70.1%) agreed totally or partially that it was necessary to address their dementia patients on living will and power of attorney; GPs who were more confident in communicating a dementia diagnosis reported addressing the issue of documents for the end of life more frequently (aOR: 1.97; 95%-CI: 1.17-3.33). Older GPs with greater knowledge of regional services for dementia patients also tended to address this topic more frequently. CONCLUSIONS: General practitioners make a major contribution to help dementia patients and their relatives to plan ahead at an early stage of the disease. It can be concluded from our results that GPs' knowledge and experiences about dementia and local services, as well as how to deal with those affected should be improved in order to optimise communication on living will and power of attorney as precautionary measures.

Opioid use disorder in chronic non-cancer pain in Germany: a cross sectional study.

OBJECTIVES: The DSM-5 diagnosis 'opioid use disorder' (OUD) was established to better describe and detect significant impairment or distress related to opioid use. There is no data on rates of OUD in chronic non-cancer pain (CNCP) in European countries. Therefore, our objective was to screen patients in specialised pain centres for signs of OUD. DESIGN: Cross-sectional questionnaire study. SETTING: Four outpatient pain clinics in the area of Bonn, Germany. PARTICIPANTS: n=204 patients participated in the study (response rate: 87.9%). All adult patients with opioid pain therapy >6 months for CNCP were included. Excluded were patients with malignant disease, patients who could not collect their prescription themselves due to age or multimorbidity and patients on opioid-maintenance therapy. PRIMARY AND SECONDARY OUTCOME MEASURE: Primary outcome measure was the proportion of patients with mild to severe OUD. RESULTS: One-fourth (26.5%) of participants were diagnosed with OUD. Moderate to severe disorder was found in 9.3. Young age was the only connected risk factor (OR 0.96 [95% CI 0.94 to 0.99], p: 0.003). CONCLUSIONS: OUD is a relevant diagnosis in patients on long-term opioid therapy for CNCP in the Bonn area. Careful follow-up by the attending physicians is advisable, especially in patients with moderate or severe disorder.

Challenges in diagnosing dementia in patients with a migrant background - a cross-sectional study among German general practitioners.

BACKGROUND: Diagnosing dementia, a syndrome affecting 35.6 million people worldwide, can be challenging, especially in patients with a migrant background. Language barriers and language-based diagnostic tools, cultural differences in the perception of the syndrome as well as restricted access to healthcare can influence medical care. For the first time in Germany, this study investigates whether German general practitioners (GPs) feel prepared to meet the diagnostic needs of these patient groups and whether there are challenges and support needs. METHODS: A cross-sectional study among a random sample of 982 general practitioners in Germany was conducted from October 2017 to January 2018 (response rate: 34.5%). A self-developed, written, standardised questionnaire was used. Descriptive statistics as well as multiple logistic regression analyses were performed using data of 326 GPs. RESULTS: Ninety-six percent of GPs reported having experienced barriers at least once. Uncertainties in diagnosing dementia in patients with a migrant background were indicated by 70.9%. There was no significant association between uncertainties in diagnosing dementia and GPs' sociodemographic characteristics. The most frequently reported barriers were language barriers that affected or prevented diagnostics (89.3%) and information deficits in patients with a migrant background (59.2%). Shameful interaction or lack of acceptance of the syndrome was also common (55.5%). A demand for more information about the topic was expressed by 70.6% of GPs. CONCLUSIONS: Public health measures supporting GPs in their interaction with patients with a migrant background as well as information and services for dementia patients are needed. Efforts to facilitate access to interpreting services and to focus on people with a migrant background in healthcare are necessary. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00012503 , date of registration: 05/09/2017 (German Institute of Medical Documentation and Information. German Clinical Trials Register (DRKS) 2017). Clinical register of the study coordination office of the University hospital of Bonn: ID530, date of registration: 05/09/2017 (Universitätsklinikum Bonn. Studienzentrum. UKB-Studienregister 2017).

[Advance Directives in Family Practices: Results of a Survey of GP Patients on their Care Situation]. / Patientenverfügungen in Hausarztpraxen ­ Ergebnisse einer Befragung von Hausarztpatienten zur ihrer Versorgungssituation.

BACKGROUND: Advance directives (AD) are an important tool for documentation of patients' wishes and are therefore recommended to the elderly as well as patients with chronic diseases. However, there is no standardized procedure in Germany and no guideline for counseling patients who wish to write an AD with or without health care proxy. The aim of this study was to evaluate the care situation concerning the ADs and the role of the primary care physician in drafting the document METHOD: We conducted semi-structured interviews with patients in primary care in North Rhine-Westphalia using a cross-sectional study design. RESULT: Most of the 154 patients who were interviewed (average age: 58 years; 52% female) suffered from chronic diseases (79%), and about one-third (32%) already had an AD. Fear of "loss of autonomy" was the main reason for preparing an AD. Patients without AD were generally not opposed to the concept and named procrastination (43%) as the main reason for not having prepared one. The chance for preparing an AD increased by the factor 1.08 per life-year (Odds ratio (OR): 1.08; CI: 1.04-1.11). Patients with AD mostly got advice via the internet (22%), their primary care physicians (12%) and relatives (12%). Most patients were satisfied with their AD. CONCLUSION: The majority of primary care patients do not make use of ADs. The primary care physicians play an important role in counseling and should motivate patients to complete ADs. Here, the establishment of quality standards would be desirable in the future.

Barriers in general practitioners' dementia diagnostics among people with a migration background in Germany (BaDeMi) - study protocol for a cross-sectional survey.

BACKGROUND: Considering the targeted general practitioner-centred healthcare in Germany, general practitioners (GPs) are in the best possible position to increase awareness of all sorts of dementia, an age-related syndrome with rising relevance in the future. In Germany, a doubling of the number of cases from 1.55 million up to 3 million in 2050 is predicted. Diagnostics can be challenging, especially among patients with a migration background. Complicating factors include: Language-based diagnostic tools, cultural differences in handling the syndrome and its underlying diseases as well as a differing use of the healthcare system. Because of missing research in this field in Germany, the type, frequency and intensity of barriers as well as the way GPs cope with them is unknown. That is why it's crucial to focus research on diagnostics in total and especially among this population group. METHODS: A cross-sectional study among a random sample of 1000 general practitioners in Germany is conducted in October 2017. A self-administered standardized questionnaire was developed, evaluated and send to the GP practices. A response rate of 30% is expected with one reminder letter. Descriptive statistics as well as, depending on the results, multivariable analyses will be executed. Based on these results and the stated needs, a cluster-randomized intervention study will be constructed to improve healthcare. DISCUSSION: This study is the first in Germany focusing on how dementia diagnostics in general practice is performed, what problems occur, especially because of a migration background of patients, and how GPs cope with them. Depending on the results, it should emphasize the necessity of dementia diagnostics to be adjusted to the needs of the rising amount of people with a migration background (22.5% in Germany, 2016) like concluded from international studies. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00012503 , date of registration: 05.09.2017. Clinical register of the study coordination office of the University hospital of Bonn: ID530 , date of registration: 05.09.2017.

Risk of opioid misuse in chronic non-cancer pain in primary care patients - a cross sectional study.

BACKGROUND: Efforts to improve treatment of pain using opioids have to adequately take into account their therapeutic shortcomings which involve addictiveness. While there are no signs of an "opioid epidemic" in Germany similar to that in the US, there is little data on the prevalence of prescription opioid misuse and addiction. Therefore, our objective was to screen primary care patients on long-term opioid therapy for signs of misuse of prescription opioids. METHODS: We recruited 15 GPs practices and asked all patients on long-term opioid therapy (> 6 months) to fill out a questionnaire including the "Current Opioid Misuse Measure" (COMM®), a self-report questionnaire. Patients with a malignant disease were excluded. RESULTS: N = 91 patients participated in the study (response rate: 75.2%). A third (31.5%) showed a positive COMM® - Score which represents a high risk of aberrant drug behaviour. A positive COMM® - Score showed a statistically significant correlation with a lifetime diagnosis of depression and neck pain. CONCLUSIONS: While Germany does not face an "opioid eoidemic", addictiveness of opioids should be considered when using them in chronic non-tumor pain. In our study population, almost every third patient was at risk and should therefore be followed up closely. Co-prevalence of depression is a significant issue and should always be screened for in patients with chronic pain, especially thus with aberrant drug behaviour.