Changes in Opioid Agonist Treatment Practice in Germany during the COVID-19 Pandemic: What Have Physicians Done, and What Would They Like to Keep Doing?

INTRODUCTION: Opioid agonist treatment (OAT) is the most common and most effective treatment option for persons with opioid use disorders (OUD). In Germany, the prescription of OAT medications is regulated by the Narcotic Drugs Prescription Ordinance. With the introduction of restrictions to contain the SARS-CoV-2 virus, the German OAT regulations have been amended to ensure a legal continuation of OAT for people with OUD. In this study, we aimed to examine the use of the OAT regulations in practice, the experience made by physicians prescribing OAT medications, and their perspective on OAT regulations. METHODS: Between September and December 2021, a questionnaire on the current situation and potential changes in the provision of OAT during the COVID-19 pandemic was sent out to 2,416 German physicians prescribing OAT medications. Differences between physicians with and without addiction medicine certification were analyzed. RESULTS: The response rate of physicians was 22.8%. Their average age was 57.4 (±10.1) years, and 62.3% were male. During the COVID-19 pandemic, take-home periods for stable patients have been extended by 48.2% of physicians, and 52.6% would like to maintain this prescribing practice in the future. Most physicians (71.6%) indicated that patients handled the extended take-home prescriptions predominantly responsibly. A total of 71.8% of the physicians generally did not use video consultation. A corona pandemic-related switch of the OST medication to depot buprenorphine injection did rather not occur, as 71.2% reported no patients treated with depot buprenorphine, and only 2.6% switched first-time or more patients to depot buprenorphine due to the COVID-19 pandemic. CONCLUSION: The corona situation opened up opportunities for physicians and patients and enabled change processes in OAT. Physicians had positive experiences implementing expanded take-home prescriptions for stable patients. Video contacts rarely took place, suggesting resistance to digital consultation. The number of depot buprenorphine prescriptions has not increased substantially since the pandemic's beginning and has remained at low levels. Further research is needed to assess to what extent the changes in OAT will be maintained over time and whether they will also lead to long-term benefits for OAT patients.

[Opioid Substitution Treatment in Germany: Physicians' View on the Effects of the 3rd Revision of the Narcotic Drugs Prescription Ordinance]. / Die Substitutionstherapie Opioidabhängiger in Deutschland: Auswirkungen der 3. BtMVVÄndV aus der Sicht substituierender Ärztinnen und Ärzte.

STUDY AIM: Opioid substitution treatment (OST) is the most effective drug treatment for opioid dependence worldwide. This form of therapy is also well established in Germany. Nevertheless, there are gaps in the provision of care, especially in rural areas and some states, due to a decreasing number of physicians involved in implementing the substitution programs. The 3rd revision of the Narcotic Drugs Prescription Ordinance (NDPO), which came into force in 2017, transferred medical therapeutic tasks of OST to the policy-making power of the German Medical Association. This comprehensive reform of the general conditions for OST led to greater legal certainty for this form of treatment. The present study aimed to analyze the effects of the 3rd revision of the Narcotic Drugs Prescription Ordinance from the providers' perspective. METHODS: Between August and December 2019, a questionnaire on individual experiences with the changes implemented in 3rd revision of the Narcotic Drugs Prescription Ordinance was sent by the Federal Opium Agency and the Associations of Statutory Health Insurance Physicians of the chosen federal states to 2,503 physicians implementing the substitution program in Germany as well as 563 physicians in Hamburg, Bavaria, North Rhine-Westphalia and Saxony who were not or no longer involved in this field of medical practice.The evaluation distinguished between physicians with and without further training in addiction medicine and between urban and rural districts. RESULTS: The response rate of physicians was 34.1%. The average age was 57.9 (±8.7) years, and 64.5% were male. The most relevant changes of the NDPO revision were found to be no time limit for achieving opioid abstinence (85.3%), new assessment and treatment using additional psychotropic substances (71.0%), extending take-home regulation to a maximum of 30 days (70.0%) and greater legal certainty (66.2%). Widening of consultative care up to 10 patients met with little approval (14.8%); 36.7% did not believe that care of substituted patients was assured either now or in the future. CONCLUSIONS: The NDPO revisions were considered to be relevant in terms of increased legal certainty and treatment liberties. Information was needed in rural areas, among physicians who carried out substitution therapy without advanced training in addiction medicine and physicians no longer involved in substitution therapy.

Switching opioid-dependent patients in substitution treatment from racemic methadone, levomethadone and buprenorphine to slow-release oral morphine: Analysis of the switching process in routine care.

Since 2015 slow-release oral morphine (SROM) is approved for opioid substitution treatment (OST) in Germany. The SROMOS study (efficacy and tolerability of slow-release oral morphine in opioid substitution treatment) evaluates the efficacy and safety of SROM in routine care. This article describes the switching process from racemic methadone, levomethadone and buprenorphine to SROM. Between July 2016 and November 2017 180 patients in 23 study centers in Germany were included in the prospective, non-interventional, naturalistic observational study. Patients were already in OST and switched from a previous medication to SROM. The switching process was analyzed during a period of fourteen days. Data were available for 169 participants. The switching process had a different progression depending on premedication and pre dosage. On the fourteenth day of SROM treatment patients switched from racemic methadone took an average dosage of 922.2 mg/day, from levomethadone 801.0 mg/day and from buprenorphine 626.7 mg/day. Average conversion ratio racemic methadone to SROM was 1:11.8, levomethadone to SROM 1:17.4 and buprenorphine to SROM 1:58.0. This study provides the first data on the switching process from buprenorphine to SROM. Average dose ratio racemic methadone to SROM on the fourteenth day of treatment was considerably higher than recommended in the prescribing information.

[Reasons for Long-Term Use of Benzodiazepines and Z-Drugs in Older Patients]. / Ursachen und Hintergründe der Langzeiteinnahme von Benzodiazepinen und Z-Substanzen bei älteren Patienten.

BACKGROUND: Long-term use of benzodiazepines (BZD) and Z-drugs is associated with the risk of developing dependency. Many older patients use these drugs for long durations, which is often associated with low-dose dependency without an increase in dose. AIM: The aim of this study is to investigate the reasons, symptoms, and side effects, as well as the prescription conditions among older patients who were prescribed BZD or Z-drugs within the last 12 months. METHODS: A 9-page questionnaire was sent to 4,000 patients of the AOK-NordWest, stratified according to age group (50-56 years;>65 years) and intake behavior (long-term use/ guideline incompatible; short-term use/ guideline compatible). Patients provided demographic data and indicated on a comprehensive list of BZD and Z-drugs, which substances they had used or were currently using. In addition, patients were asked about the reasons and underlying symptoms for taking these medications, possible side effects, and previous attempts to discontinue the medications. RESULTS: A total of 466 patients returned completed questionnaires (11.7%). A further 43 privately insured patients were recruited through pharmacies. 169 patients, mainly from the group with guideline-compatible prescriptions, indicated that they had never taken these medications. The remaining 340 patients were 68.5% female and the average age was 72.1 years. Compared to patients with guideline-compatible prescriptions, a greater proportion of patients with guideline-incompatible prescriptions were taking Z-drugs. The average daily dose (DDD) consumed was significantly higher than in those with guideline-compatible prescriptions, although on average both patient groups took low doses (<1 DDD) of the medication. In both groups, the main reason for taking BZD and Z-drugs was sleeping problems. CONCLUSIONS: Considering the recommendation that BZD and Z-drugs are to be taken only short-term for sleeping problems, the extent of insomnia indications is high. The low doses suggest a careful and controlled prescription behavior in both groups, with the majority of long-term consumers likely to have developed low-dose dependency. This is associated with only a limited need for intervention, since only few medication-dependent people underwent addiction treatment.

Electronic Cigarettes in Germany: Patterns of Use and Perceived Health Improvement.

AIMS: The aim of the study was to characterize e-cigarette users in terms of their consumption patterns, motives, and the perceived health benefits they experience from using e-cigarettes. DESIGN: The study was a cross-sectional online survey in 2015. A total of 3,320 German e-cigarette users were enrolled. A total of 91.5% were former tobacco smokers, 7.5% used both e-cigarettes and tobacco products, 1.0% were never-smokers. RESULTS: No differences were found between ex-smokers and dual users with regard to sociodemographic and smoking history (mean age 40.8 years, 81% men, 45% with a high school degree or above). Both groups had smoked 26.4 tobacco cigarettes a day for 22 years, had unsuccessfully tried to quit smoking using various other nicotine replacement products, and had used e-cigarettes for an average of 2 years. Ex-smokers consumed lower nicotine strength and more liquid per month, experienced more positive health changes, and had made vaping their hobby. Never-smokers were about 5 years younger, used liquid without nicotine and without tobacco flavor, and had no physical dependency. CONCLUSIONS: E-cigarettes were primarily used as an alternative to smoking and a substitute for nicotine. More dual users than ex-smokers used e-cigarettes in places where smoking is forbidden. Positive health changes were more pronounced in ex-smokers than dual users.

Silicon- and Tin-Containing Open-Chain and Eight-Membered-Ring Compounds as Bicentric Lewis Acids toward Anions.

Herein, we report the syntheses of silicon- and tin-containing open-chain and eight-membered-ring compounds Me2 Si(CH2 SnMe2 X)2 (2, X=Me; 3, X=Cl; 4, X=F), CH2 (SnMe2 CH2 I)2 (7), CH2 (SnMe2 CH2 Cl)2 (8), cyclo-Me2 Sn(CH2 SnMe2 CH2 )2 SiMe2 (6), cyclo-(Me2 SnCH2 )4 (9), cyclo-Me(2-n) Xn Sn(CH2 SiMe2 CH2 )2 SnXn Me(2-n) (5, n=0; 10, n=1, X=Cl; 11, n=1, X=F; 12, n=2, X=Cl), and the chloride and fluoride complexes NEt4 [cyclo- Me(Cl)Sn(CH2 SiMe2 CH2 )2 Sn(Cl)Me⋅F] (13), PPh4 [cyclo-Me(Cl)Sn(CH2 SiMe2 CH2 )2 Sn(Cl)Me⋅Cl] (14), NEt4 [cyclo-Me(F)Sn(CH2 SiMe2 CH2 )2 Sn(F)Me⋅F] (15), [NEt4 ]2 [cyclo-Cl2 Sn(CH2 SiMe2 CH2 )2 SnCl2 ⋅2 Cl] (16), M[Me2 Si(CH2 Sn(Cl)Me2 )2 ⋅Cl] (17 a, M=PPh4 ; 17 b, M=NEt4 ), NEt4 [Me2 Si(CH2 Sn(Cl)Me2 )2 ⋅F] (18), NEt4 [Me2 Si(CH2 Sn(F)Me2 )2 ⋅F] (19), and PPh4 [Me2 Si(CH2 Sn(Cl)Me2 )2 ⋅Br] (20). The compounds were characterised by electrospray mass-spectrometric, IR and (1) H, (13) C, (19) F, (29) Si, and (119) Sn NMR spectroscopic analysis, and, except for 15 and 18, single-crystal X-ray diffraction studies.

[Opioid agonist therapy and the German Narcotic Drugs Prescription Ordinance from the pharmacist's perspective]. / Opioidsubstitutionstherapie im Rahmen der neuen Betäubungsmittel-Verschreibungsverordnung aus Sicht von Apothekerinnen und Apothekern.

BACKGROUND: Opioid agonist therapy (OAT) has been established to be the most important therapy option for improving health and social burdens of people with opioid dependence. Pharmacies provide drug substitutes to substitution practices or outpatient clinics and administer drugs to substituted patients (medication under visual control) or supply prescriptions for unsupervised, at-home use by patients. Given the gaps in medical care, the relevance of pharmacies for the comprehensive treatment of opioid-dependent patients will become even more important in the future. The 3rd Revision of the Narcotic Drugs Prescription Ordinance (NDPO) adopted sweeping reforms to the framework of OAT in 2017. This paper examines the impact of this reform from the pharmacist's perspective. METHODS: Between November 2020 and March 2021, pharmacists in the German federal states of Hamburg, North-Rhine Westphalia, Saxony, and Bavaria were informed by their State Chambers of Pharmacists about participation in this online study. A total of 480 questionnaires were evaluated. The analysis differentiates between pharmacists who are currently involved in the substitution of opioid-dependent patients (54.2%), pharmacists who were involved in the past (21.4%), and those who have never been involved in opioid substitution (24.4%). RESULTS: Pharmacists involved in OAT have not seen any positive changes resulting from the 3rd Revision of the NDPO. According to 97.9% of the pharmacists, remuneration for administering medication under visual control should be analogous to remuneration in doctors' practices. Mixed prescriptions (prescription of take-home dose and intermediate medication under visual control) increase the administrative workload and have been rejected by a quarter of the pharmacists. Non-involved pharmacists significantly overestimated the occurrence of critical situations with substituted patients in the pharmacy. While only 2.7% of pharmacists involved in OAT reported drug emergencies, 23.1% of non-involved pharmacists expressed such concerns. 39.3% of the pharmacists felt they could be motivated to participate in OAT if they were approached directly, and 73.9% of the pharmacists who are currently involved in OAT said they could provide substitution medication under visual control to additional opioid-dependent patients. CONCLUSIONS: The 3rd Revision of the NDPO has no influence on the situation and willingness of pharmacists to be involved in OAT. However, to ensure that pharmacists continue to be actively involved in OAT and attract new substituting pharmacies, their importance for comprehensive OAT must be upgraded. This includes, and not least, the funding of pharmacists' administration of substitution drugs under visual control. In addition, knowledge about OAT, attitudes toward opioid-dependent patients, and contact anxiety could be addressed by promoting educational awareness and training.

Substitution treatment for opioid dependence with slow-release oral morphine: Retention rate, health status, and substance use after switching to morphine.

INTRODUCTION: Since April 2015, slow-release oral morphine (SROM) has been approved for opioid agonist treatment (OAT) in Germany. Experimental studies show that benefits of SROM over methadone include less heroin craving, better tolerability, and higher patient satisfaction and mental stability. The SROMOS study (Efficacy and Tolerability of Slow-Release Oral Morphine in Opioid Substitution Treatment) aims to investigate the long-term effects (effectiveness and safety) of morphine substitution under routine care in Germany. MATERIAL AND METHODS: This is a prospective, noninterventional, naturalistic, observational study. Between July 2016 and November 2017, this study recruited patients in OAT who decided to switch to SROM from 23 outpatient addiction treatment centers in Germany. The study collected data on mental health (Brief Symptom Inventory - BSI-18), substance use, somatic health (Opiate Treatment Index Health-Symptoms-Scale - OTI-HSS), opioid craving (visual analogue scale), and withdrawal symptoms (Short Opiate Withdrawal Scale) at baseline (t0) and after 3 (t3), 6 (t6) and 12 (t12) months. Physicians documented side effects as adverse events (AEs) and adverse drug reactions (ADRs). RESULTS: Three-quarters of the enrolled study participants (N = 180) were male. The average age was 44.4 years. Patients were opioid-dependent for 23 years and had been in OAT for almost seven years on average. After 12 months, 60.6% were still being treated with SROM. Mental health improved significantly under SROM treatment between t0 and t12. The intention-to-treat (ITT), as well as the per-protocol (PP) analysis, shows a statistically significant improvement of the mean Global Severity Index (GSI) of the BSI-18 value of 20% (ITT) and 24% (PP). Physical health also improved significantly under SROM treatment. There were no statistically significant changes in the use of cannabis, cocaine, amphetamines, and tranquillizers in the past 30 days, but heroin use, intravenous consumption, and the number of drinking days significantly decreased. CONCLUSIONS: This study provides some of the first long-term data on OAT with SROM under routine care conditions. SROM treatment is an effective alternative for a subgroup of opioid-dependent patients with an unsatisfactory course of OAT or in cases where undesirable side effects due to alternative substances have occurred. ETHICAL STATEMENT: The study protocol was approved by the Ethics Committee of the Chamber of Physicians in Hamburg in March 2016 (No. PV5222). The study was conducted by following the Declaration of Helsinki and is registered with the German Register of Clinical Trials (DRKS, ID: DRKS00010712).

Implication of gender differences in heroin-assisted treatment: results from the German randomized controlled trial.

Despite a lower prevalence of opioid dependence among females, drug-related problems and risk factors such as prostitution have a negative effect for women in treatment. This study was conducted with the purpose of analyzing gender differences in the German trial on heroin-assisted treatment (HAT), which compared HAT with methadone maintenance treatment (MMT). Significant baseline gender differences were found, with females showing a greater extent of mental distress. Differences in retention and outcome were significant for male patients, but no differences between treatment options were found for female patients. Ongoing prostitution was found to influence drug use outcomes. Other outcome criteria may need to be stressed when assessing the effect of HAT for women.

Oxazepam versus clomethiazol in alcohol withdrawal treatment.

The pharmacological management of the alcohol withdrawal syndrome associated with alcohol dependence is heterogeneous; however, according to the guidelines, clomethiazol is the standard medication in Germany. Benzodiazepines offer another safe possibility of treating alcohol withdrawal. In a retrospective study, alcohol-dependent patients treated either with oxazepam (n = 141) or clomethiazol (n = 357) were assessed with respect to the course of treatment and withdrawal symptoms. The results showed that under oxazepam treatment, there were fewer days with severe alcohol withdrawal symptoms and less severe adverse events, but patients receiving clomethiazol treatment had a more severe course of alcohol dependence. Oxazepam is a safe, efficient and cheap drug for the treatment of alcohol withdrawal symptoms, but controlled studies are needed to compare its effectiveness with that of clomethiazol.

Long-term use of benzodiazepines and Z drugs: a qualitative study of patients' and healthcare professionals' perceptions and possible levers for change.

BACKGROUND: Although long-term use of benzodiazepines (BZDs) and Z drugs is associated with various side effects, they remain popular among the older population. Possible reasons for this phenomenon could be ineffective ways of transmitting information on the health risks associated with long-term use, and communication gaps between patients and healthcare professionals. AIM: The aim was to investigate the views of patients, physicians, nurses, and pharmacists regarding long-term BZD and Z drug use. DESIGN & SETTING: The qualitative study design used focus group interviews with physicians, pharmacists, and nurses in Hamburg. Patient interviews were conducted in Lippstadt, Germany. METHOD: The interviews were audiotaped with each participant's permission, transcribed, and thematically analysed using a software program for qualitative research (MAXQDA). RESULTS: The data from the four focus groups consisting of 28 participants were analysed. Patients indicated lack of knowledge about risks and side effects, difficult access to alternatives, and fears of ceasing drug use without professional support. Although the physicians were reported to be cautious about prescribing BZDs and Z drugs, the psychosocial problems of older patients are often considered to be complex and treatment knowledge, experience, and resources are frequently unsatisfactory. Nurses described that when BZDs were prescribed, they did not feel it was their responsibility to evaluate their effects. Pharmacists were reported to be strongly ambivalent in informing patients about the risks, which may contradict the prescription advice provided by the physician. CONCLUSION: Patients, physicians, nurses, and pharmacists reported differences in the perception of long-term BZD and Z drug use. Nevertheless, all of the participants described lack of information and expressed the need for greater communication exchange.

[Treatment of Alcohol Withdrawal Syndrome with Oxazepam or Clomethiazole - A Naturalistic Observational Study]. / Die Behandlung des Alkoholentzugs mit Oxazepam oder Clomethiazol ­ eine naturalistische Beobachtungsstudie.

Whilst internationally benzodiazepines are first choice for treatment of alcohol withdrawal syndrome, Germany has a long tradition with clomethiazole. This study explores effectiveness of clomethiazole versus oxazepam in the treatment of alcohol withdrawal syndrome within an observational, stratified, non-inferiority study in routine care. Main outcome criterion was severity of the alcohol withdrawal syndrome (Alcohol Withdrawal Syndrome [AWS]) Scale in the first five days. Additionally, the association between the detoxification protocol (five vs. ten days) and AWS-Score was examined. 453 patients (74.2 % male, average age 47.1 years [±â€Š9.2]) took part; 249 received oxazepam (55.0 %) and 204 clomethiazole (45.0 %). The average duration of inpatient treatment was 14.0 days (±â€Š6.3) in both groups. The average AWS-score was lower in the oxazepam group compared to the clomethiazole group (50.0 [±â€Š26.5] vs. 56.2 [±â€Š31.5]; p < .05; effect size d = - .25). Patients with a shorter detoxification protocol had a lower AWS sum score compared to patients with a longer protocol (p < .001; d = - .46). In treatment of alcohol withdrawal syndrome in routine care oxazepam yields at least comparable results to clomethiazole.

Potentially inappropriate use of benzodiazepines and z-drugs in the older population-analysis of associations between long-term use and patient-related factors.

INTRODUCTION: The long-term use of benzodiazepines (BZD) and z-drugs in older populations is associated with a variety of sociodemographic and health-related factors. Recent studies reported that long-term BZD and z-drugs use is associated with increased age, female sex, and severe negative psychological (e.g., depression) and somatic (e.g., chronic disease) factors. The current study explores the sociodemographic and health-related factors associated with long-term BZD and z-drugs use in the elderly. METHODS: We conducted a cross-sectional survey among randomly selected patients of one health insurance plan ("AOK North-West") with BZD and z-drugs prescriptions in the past 12 months. The sample was stratified by appropriate German prescription guidelines (yes vs. no) and age (50-65 vs. >65 years). To examine the association of selected sociodemographic and psychological variables (e.g., sex, employment status, quality of life, depression) with long-term use, a binary logistic regression analysis was conducted. RESULTS: In total, data from 340 patients were analyzed. The mean age was 72.1 (SD = 14.5) years, and the most commonly used substances were zopiclon (38.1%), oxazepam (18.1%), and lorazepam (13.8%). The mean defined daily dose (DDD) was 0.73 (SD = 0.47). Insomnia was the main reason for prescribing BZD and z-drugs. The long-term use of BZD and z-drugs was significantly associated with unemployment (OR = 2.9, 95% CI [1.2-7.1]) and generally problematic medication use (OR = 0.5, 95% CI [0.2-1.0]). DISCUSSION: Unemployment status and problematic medication use had a significant association with the patient-reported, long-term use of BZD and z-drugs. Divergent prescription patterns might suggest problematic patterns of BZD and z-drugs use. The causal connection between the identified factors and problematic BZD and z-drugs prescription is not discussed in this paper. Nevertheless, employment status and possible evidence of general problematic drug use may be a warning signal to the prescribers of BZD and z-drugs.

Patient-centered care interventions to reduce the inappropriate prescription and use of benzodiazepines and z-drugs: a systematic review.

BACKGROUND: Benzodiazepines (BZDs) and z-drugs are effective drugs, but they are prescribed excessively worldwide. International guidelines recommend a maximum treatment duration of 4 weeks. Although these drugs are effective in the short-term, long-term BZD therapy is associated with considerable adverse effects, the development of tolerance and, finally, addiction. However, there are different interventions in terms of patient-centered care that aim to reduce the use of BZDs and z-drugs as well as assist health care professionals (HCPs) in preventing the inappropriate prescription of BZDs. AIM: The aim of this systematic review was to identify interventions that promote patient-centered treatments for inappropriate BZD and z-drug use and to analyze their effectiveness in reducing the inappropriate use of these drugs. METHODS: To identify relevant studies, the PubMed, EMBASE, PsycINFO, Psyndex, and Cochrane Library databases were searched. Studies with controlled designs focusing on adult patients were included. Trials with chronically or mentally ill patients were excluded if long-term BZD and z-drug use was indicated. Study extraction was performed based on the Cochrane Form for study extraction. To assess the quality of the studies, we used a tool based on the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials. RESULTS: We identified 7,068 studies and selected 20 for systematic review. Nine interventions focused on patients, nine on HCPs, and two on both patients and HCPs. Intervention types ranged from simple to multifaceted. Patient-centered interventions that provided patient information effectively increased the appropriate use of BZDs. The educational approaches for HCPs that aimed to achieve appropriate prescription reported inconsistent results. The methods that combined informing patients and HCPs led to a significant reduction in BZD use. CONCLUSIONS: This is the first review of studies focused on patient-centered approaches to reducing the inappropriate prescription and use of BZDs and z-drugs. The patient-centered dimension of patient information was responsible for a decrease in BZD and z-drug consumption. Further, in some studies, the patient-centered dimensions responsible for reducing the prescription and use of BZDs and z-drugs were the clinician's essential characteristics and clinician-patient communication.

Nerve growth factor in serum is a marker of the stage of alcohol disease.

Long-term alcohol abuse has deleterious effects on the peripheral and central nervous system. Nerve growth factor (NGF) is a pleiotropic neurotrophic protein involved in development, maintenance of function and regeneration of nerve cells. We examined patients in different stages of alcohol disease and measured their NGF serum concentrations based on the hypothesis that these reflect the state of disease. We examined 57 patients suffering from alcohol-dependence for more than 2 years (DSM IV) on day 8 of a qualified withdrawal, 18 patients with Korsakoff's syndrome and 40 healthy controls. In addition to clinical examination, careful history taking and a standard neuropsychological test battery, serum NGF concentrations were measured by a highly sensitive enzyme-immunoassay. Of the 57 patients 9 had suffered from severe withdrawal delirium in the past, other clinical parameters were alike. Cognitive test performance did not differ from the control group. Mean NGF levels of controls amounted to 42.1pg/ml (S.D. 68.0); mean levels of patients with alcohol dependence were raised significantly to 401.5pg/ml (S.D. 932.6) without delirium in the past and even further to 3292.5pg/ml (S.D. 4879.6) with former withdrawal delirium. By contrast, patients with persistent amnestic disorder (Korsakoff's syndrome) showed values identical to the controls. NGF serum levels were significantly elevated in alcohol-dependent patients, more so in those with prior delirium. Their cognitive tests being normal, this possibly reflects the activity of NGF as an endogenous repair mechanism for damaged neurons. In accordance with this hypothesis, NGF values are "normal" in patients with persistent alcohol-related cognitive decline.

Meta-analysis on the effectiveness of alcohol screening with brief interventions for patients in emergency care settings.

BACKGROUND AND AIMS: Despite ambiguous evidence for the effectiveness of alcohol screening with brief interventions (BI) in emergency departments (ED), ambition for their widespread implementation continues to grow. To clarify whether such an application of BI is justifiable, we conducted a systematic review and meta-analysis on studies testing the impact of BI on alcohol consumption. METHODS: We included peer-reviewed, randomized controlled studies investigating the effects of BI on alcohol consumption in injured and/or intoxicated patients, published January 2002-September 2015. Changes from baseline in consumption quantity, intensity and number of heavy drinking episodes were assessed at 3-, 6- and 12-month follow-up, resulting in nine separate random-effects meta-analyses of standardized mean differences (SMD). Moderation effects of intervention mode, length, type of interventionist, intensity of control intervention and study quality were assessed using subgroup comparisons and meta-regression. RESULTS: We considered 33 publications (28 separate studies) including 14 456 patients. Six of nine comparisons revealed small significant effects in favour of BI, with the highest SMD at 0.19 [95% confidence interval (CI) = 0.08-0.31]. No significant moderators could be identified, and statistical heterogeneity (I(2) ) was below 40%. CONCLUSIONS: In a large meta-analysis of randomized controlled trials in emergency care settings, there was evidence for very small effects of brief interventions on alcohol consumption reductions. More intensive interventions showed no benefit over shorter approaches. Non-face-to-face interventions appear to be comparably effective, but this finding remains tentative due to the low number of non-face-to-face studies.

Lisuride, a dopamine D2 receptor agonist, and anticraving drug expectancy as modifiers of relapse in alcohol dependence.

Due to a central role of dopamine in mediating ethanol intake and dependence, the authors tested lisuride, a dopamine D2 receptor agonist, for relapse prevention in alcoholics. Psychological and neuroendocrine determinants of outcome were also assessed within the study. This double-blind, placebo-controlled randomized study comprised 120 alcoholics who were subjected to an intend-to-treat analysis (ITT). After hospital detoxification, patients received an outpatient rehabilitation program and either the study medication or placebo for 6 months and follow-up for another 6 months without medication. Pharmacological and psychological effects on relapse and times to first drink were assessed using survival analysis and multivariate analysis of variance (ANOVA). Neuroendocrine assessments were made using growth hormone (GH) response to stimulation with dopamine D2 receptor agonist apomorphine. In contrast to our hypothesis, the pharmacological effects of lisuride shortened (effect size: 0.51) and the expectation of receiving the drug (while being on medication) prolonged the latency of relapse (effect size: 0.47) in weaned alcoholics. Lisuride was associated with side effects like dizziness and hypotension. Dopaminergic responsivity to apomorphine stimulation was reduced under lisuride. This study supports the view that alcoholics may relapse due to decreased dopamine function, resulting from intake of dopamine D2 receptor agonists. In particular, our data do not support the use of lisuride for relapse prevention in alcoholics. The favorable impact of anticraving drug expectancy on outcome was unrelated to this effect.

Investigating the stability of the nonionic surfactants tocopheryl polyethylene glycol succinate and sucrose laurate by HPLC-MS, DAD, and CAD.

High-performance liquid chromatography (HPLC) methods using a charged aerosol detector (CAD), a mass selective detector (MSD), and a diode array detector (DAD) were developed to characterize the nonionic surfactants d-α-tocopheryl polyethylene glycol (1000) succinate (TPGS) and Surfhope sugar ester D-1216 (sucrose laurate). The molecular structure and the heterogeneous composition resulting from different isomers and various lengths of polyethylene glycol (PEG) chains make it difficult to develop sensitive and specific analytical methods for both surfactants. Hence, there is lack of knowledge about the stability and grade of impurity of these compounds. Sucrose laurate does not possess any chromophore, thus UV detection is not applicable. Therefore, CAD and MSD have been used for determination. The aim of the study was to characterize these nonionic surfactants and to examine chemical stability at pH 1.0 and 37 °C, simulating harsh gastric conditions. It was shown that both compounds are liable to degradation under these conditions. Sucrose monolaurate exhibited a massive degradation within 8 h incubation due to cleavage of the glycosidic bondage. About 50% of sucrose monolaurate broke down, whereas a marginal amount of 3.4% (± 0.4%) of TPGS degraded into d-α-tocopheryl succinate and the associated PEG chain.