Intermittent hemodialysis treatment in cefepime-induced neurotoxicity: Case report, pharmacokinetic modeling, and review of the literature.

Cefepime is a broad-spectrum cephalosporin indicated for in-hospital treatment of severe infections. Acute neurotoxicity, an increasingly recognized adverse effect of this drug in an overdose, predominantly affects patients with reduced renal function. Although dialytic approaches have been advocated to treat this condition, their role in this indication remains unclear. We report the case of an 88-year-old female patient with impaired renal function who developed life-threatening neurologic symptoms during cefepime therapy. She was treated with two intermittent 3-hour high-flux, high-efficiency hemodialysis sessions. Serial pre-, post-, and peridialytic (pre- and postfilter) serum cefepime concentrations were measured. Pharmacokinetic modeling showed that this dialytic strategy allowed for serum cefepime concentrations to return to the estimated nontoxic range 15 hours earlier than would have been the case without an intervention. The patient made a full clinical recovery over the next 48 hours. We conclude that at least 1 session of intermittent hemodialysis may shorten the time to return to the nontoxic range in severe clinically patent intoxication. It should be considered early in its clinical course pending chemical confirmation, even in frail elderly patients. Careful dosage adjustment and a high index of suspicion are essential in this population.

A high proportion of users of low-threshold facilities with needle exchange programmes in Switzerland are currently on methadone treatment: implications for new approaches in harm reduction and care.

BACKGROUND: Increasingly, patients receiving methadone treatment are found in low threshold facilities (LTF), which provide needle exchange programmes in Switzerland. This paper identifies the characteristics of LTF attendees receiving methadone treatment (MT) compared with other LTF attendees (non-MT). METHODS: A national cross-sectional survey was conducted in 2006 over five consecutive days in all LTF (n=25). Attendees were given an anonymous questionnaire, collecting information on socio-demographic indicators, drug consumption, injection, methadone treatment, and self-reported HIV and HCV status. Univariate analysis and logistic regression were performed to compare MT to non-MT. The response rate was 66% (n=1128). RESULTS: MT comprised 57.6% of the sample. In multivariate analysis, factors associated with being on MT were older age (OR: 1.38), being female (OR: 1.60), having one's own accommodation (OR: 1.56), receiving public assistance (OR: 2.29), lifetime injecting (OR: 2.26), HIV-positive status (OR: 2.00), and having consumed cocaine during the past month (OR: 1.37); MT were less likely to have consumed heroin in the past month (OR: 0.76, not significant) and visited LTF less often on a daily basis (OR: 0.59). The number of injections during the past week was not associated with MT. CONCLUSIONS: More LTF attendees were in the MT group, bringing to light an underappreciated LTF clientele with specific needs. The MT group consumption profile may reflect therapeutic failure or deficits in treatment quality and it is necessary to acknowledge this and to strengthen the awareness of LTF personnel about potential needs of MT attendees to meet their therapeutic goals.

Oral and intravenous methadone use: some clinical and pharmacokinetic aspects.

A sample of 15 patients participating in an injectable methadone trial and of 15 patients in an oral methadone maintenance treatment, who admitted injecting part or all of their methadone take-home doses, were compared to 20 patients in maintenance treatment who use methadone exclusively by mouth. The present study confirms the poorer general health, the higher levels of emotional, psychological or psychiatric problems, the higher use of illicit drugs, and the higher number of problems related to employment and support associated with the use of the intravenous mode of administration of methadone. As expected, due to the shunt of metabolism in the gut wall and of the liver first-pass effect, higher concentration to dose ratios of (R)-methadone, which is the active enantiomer, were measured in the intravenous group (23% increase). This difference reached an almost statistically significant value (P = 0.054). This raises the question whether the effect of a higher methadone dose could be unconsciously sought by some of the intravenous methadone users.

Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer

A very long half-life of paroxetine (195 h instead of the usual value of around 16 h) was measured after an overdose with 2 g paroxetine and 1 g clorazepate in a patient who was an extensive cytochrome P4502D6 metabolizer. The patient recovered well without any clinically significant complications. A consequence of the close monitoring of paroxetine levels in this patient was that it was decided not to reintroduce any other antidepressant despite her suicide attempt, until normal levels of paroxetine had been reached, which took over 1 month.

Supervised injection services : what has been demonstrated? A systematic literature review

BACKGROUND: Supervised injection services (SISs) have been developed to promote safer drug injection practices, enhance health-related behaviors among people who inject drugs (PWID), and connect PWID with external health and social services. Nevertheless, SISs have also been accused of fostering drug use and drug trafficking. AIMS: To systematically collect and synthesize the currently available evidence regarding SIS-induced benefits and harm. METHODS: A systematic review was performed via the PubMed, Web of Science, and ScienceDirect databases using the keyword algorithm [("supervised" or "safer") and ("injection" or "injecting" or "shooting" or "consumption") and ("facility" or "facilities" or "room" or "gallery" or "centre" or "site")]. RESULTS: Seventy-five relevant articles were found. All studies converged to find that SISs were efficacious in attracting the most marginalized PWID, promoting safer injection conditions, enhancing access to primary health care, and reducing the overdose frequency. SISs were not found to increase drug injecting, drug trafficking or crime in the surrounding environments. SISs were found to be associated with reduced levels of public drug injections and dropped syringes. Of the articles, 85% originated from Vancouver or Sydney. CONCLUSION: SISs have largely fulfilled their initial objectives without enhancing drug use or drug trafficking. Almost all of the studies found in this review were performed in Canada or Australia, whereas the majority of SISs are located in Europe. The implementation of new SISs in places with high rates of injection drug use and associated harms appears to be supported by evidence.

Management of hepatitis C virus (HCV) infection in drug substitution programs.

BACKGROUND: In Switzerland, intravenous drug use (IDU) accounts for 80% of newly acquired hepatitis C virus (HCV) infections. Early HCV treatment has the potential to interrupt the transmission chain and reduce morbidity/mortality due to decompensated liver cirrhosis and hepatocellular carcinoma. Nevertheless, patients in drug substitution programs are often insufficiently screened and treated. OBJECTIVE/METHODS: With the aim to improve HCV management in IDUs, we conducted a cross sectional chart review in three opioid substitution programs in St. Gallen (125 methadone and 71 heroin recipients). Results were compared with another heroin substitution program in Bern (202 patients) and SCCS/SHCS data. RESULTS: Among the methadone/heroin recipients in St. Gallen, diagnostic workup of HCV was better than expected: HCV/HIV-status was unknown in only 1% (2/196), HCV RNA was not performed in 9% (13/146) of anti-HCV-positives and the genotype missing in 15% (12/78) of HCV RNA-positives. In those without spontaneous clearance (two thirds), HCV treatment uptake was 23% (21/91) (HIV-: 29% (20/68), HIV+: 4% (1/23)), which was lower than in methadone/heroin recipients and particularly non-IDUs within the SCCS/SHCS, but higher than in the, mainly psychiatrically focussed, heroin substitution program in Bern (8%). Sustained virological response (SVR) rates were comparable in all settings (overall: 50%, genotype 1: 35-40%, genotype 3: two thirds). In St. Gallen, the median delay from the estimated date of infection (IDU start) to first diagnosis was 10 years and to treatment was another 7.5 years. CONCLUSIONS: Future efforts need to focus on earlier HCV diagnosis and improvement of treatment uptake among patients in drug substitution programs, particularly if patients are HIV-co-infected. New potent drugs might facilitate the decision to initiate treatment.

Carotid sparing in t1-t2 no glottic cancer using helical tomotherapy

Objective: To study the dosimetric properties and clinical implementation of a carotid dose sparing irradiation protocol using helical Tomotherapy in early stage laryngeal cancer.Materials and Methods: We have developed a simple treatment planning algorithm for carotid sparing. We have compared carotid and critical organ doses and planned target volume (PTV) dose with our standard laryngeal irradiation protocol. Dose constraints were the following: maximum point dose to the carotids <35 Gy, to the spinal cord <30 Gy, and PTV was covered at >95% of the prescribed dose (70 Gy in 2 Gy per fraction). A daily megavoltage CT was done to account for patient movement and anatomy modification. To date, 7 patients have been treated with this protocol in our department.Results: Our early results showed a significant reduction in the carotid dose with an average maximum dose of 35.8 Gy. The average maximum spinal cord dose was 25.8 Gy. PTV was covered without important "hot spots". Average maximum dose in the PTV was 74.1 Gy with an average absolute maximum dose of 75.2 Gy. To date, the clinical outcomes have been excellent.Conclusion: Helical Tomotherapy allows a significant decrease of carotid dose without dangerous spinal cord overdose. There was no important overdose in the PTV that can potentially increase the late complication risks. Daily control imaging brings added security especially when working with such high-dose gradients. We think further studies and longer follow-up are needed to investigate the clinical outcomes such as the local control rate and the vascular late toxicities.

Psychopathologie chez les enfants de patients souffrant de troubles liés à une substance ou de troubles de l'humeur

L'objectif principal de cette thèse est d'exposer les résultats des premières évaluations psychopathologiques menées, dans le cadre d'une étude familiale, sur une cohorte d'enfants de patients souffrant de troubles liés à des substances ou de troubles de l'humeur. Plus précisément, nous avons examiné des enfants de patients souffrant de dépendance à l'alcool et à l'héroïne, de troubles bipolaires et unipolaires, ainsi qu'un groupe d'enfants témoins, dont les parents étaient des patients contrôles recrutés dans des départements d'orthopédie. Nous nous sommes ainsi proposé d'étudier de façon précise le risque de psychopathologie chez des enfants de parents malades en menant une étude longitudinale prospective au moyen d'évaluations standardisées. Ces enfants ainsi que leurs parents-patients (probands) sont actuellement évalués chaque trois ans. Nous avons aussi effectué une évaluation des co-parents biologiques de ces enfants afin de tenir compte également de l'impact de leurs éventuels troubles psychiatriques sur les manifestations psychopathologiques de leurs enfants. Le volet longitudinal-prospectif de ces familles est actuellement en cours, et les deux articles contenus dans cette thèse, publiés dans des revues à politique éditoriale, exposent les résultats obtenus lors de l'évaluation initiale de ces enfants et de leurs deux parents. Nous résultats montrent que les enfants de patients, pourtant encore très jeunes (moyenne d'âge d'environ 11 ans), présentent déjà de plus hauts taux de manifestations psychopathologiques que les enfants de parents contrôles. Nous avons également pu démontrer le rôle joué par le co-parent, en plus de celui du parent-patient, dans le développement de psychopathologie chez ces enfants. Ces résultats soulignent la nécessité d'une identification et d'une prise en charge très précoce de ces enfants, et indiquent également l'importance de porter un intérêt clinique non seulement au parent-patient, mais également au co-parent de ces enfants. - This thesis presents the baseline results of psychopathological assessments conducted in a prospective longitudinal cohort study of children whose parents have substance use disorders or mood disorders. More specifically, we examined children of alcohol- and heroin- dependent patients, children of patients with bipolar or unipolar disorders, and, as a control group, children whose parents were recruited in orthopedics departments. Using standardized assessments, we conducted this study to accurately assess the risk of psychopathology in children of parents with these substance use or mood disorders. The prospective longitudinal study of these families is currently ongoing, with the children and their parent-patients (probands) being followed up every three years. We also assessed the biological co-parent in order to determine the impact of their possible psychiatric disorders on the risk of mental disorders in offspring. The two articles of this thesis, which have been published in peer-reviewed journals, present the results of baseline assessments of the children and their two parents. Our results show that the children of patients who are still very young at baseline assessment (mean age about 11 years) already have higher rates of psychopathological manifestations compared with children of control parents. We also demonstrate the effect of the co-parents, in addition to that of the parent-patients, on the development of early psychiatric manifestations in these children. These results emphasize the importance of prompt identification and treatment of these children and highlight the need for clinical care not only of the patient, but also of the co- parent, in order to optimize the prevention of mental disorders in their offspring.

Death following acute poisoning by moclobemide

A fatality due to ingestion of a reversible inhibitor of monoamine-oxidase A (MAO-A) is reported. Moclobemide is generally considered as a safe drug far less toxic than tricyclic anti-depressants. However, severe intoxications may result from interactions with other drugs and food such as selective serotonin reuptake inhibitors (SSRIs), anti-Parkinsonians of the MAOI-type (e.g. selegiline) or tyramine from ripe cheese or other sources. In the present case, high levels of moclobemide were measured in peripheral blood exceeding toxic values reported so far in the scientific literature. The body fluid concentrations of moclobemide were of 498 mg/l in peripheral whole blood, 96.3 mg/l in urine while an amount of approximately 33 g could be recovered from gastric contents. The other xenobiotics were considered of little toxicological relevance. The victim (male, 48-year-old) had a past history of depression and committed one suicide attempt 2 years before death. Autopsy revealed no evidence of significant natural disease or injury. It was concluded that the manner of death was suicide and that the unique cause of death was massive ingestion of moclobemide.

Patterns and transitions in substance use among young Swiss men: a latent transition analysis approach

This study investigates the potential stages of drug use. Data from the longitudinal Cohort Study on Substance Use Risk Factors were used (N = 5,116). Drug use (alcohol, tobacco, and 16 illicit drugs) over the previous 12 months was assessed at two time points. Patterns and trajectories of drug use were studied using latent transition analysis (LTA). This study's substantive contributions are twofold. First, the pattern of drug use displayed the well-known sequence of drug involvement (licit drugs to cannabis to other illicit drugs), but with an added distinction between two kinds of illicit drugs ("middle-stage" drugs: uppers, hallucinogens, inhaled drugs; and "final-stage" drugs: heroin, ketamine, GHB/GBL, research chemicals, crystal meth, and spice). Second, subgroup membership was stable over time, as the most likely transition was remaining in the same latent class.

Measurement of β-tryptase in postmortem serum, pericardial fluid, urine and vitreous humor in the forensic setting.

In the realm of forensic pathology, β-tryptase measurement for diagnostic purposes is performed in postmortem serum obtained from femoral blood. This may be partially or completely unavailable in some specific cases, such as infant autopsies and severely damaged bodies. The aim of this study was to investigate the usefulness of determining β-tryptase levels for diagnostic purposes in alternative biological samples. Urine, vitreous humor and pericardial fluid were selected and measured in 94 subjects including: fatal anaphylaxis following contrast material administration (6 cases), hypothermia (10 cases), diabetic ketoacidosis (10 cases), gunshot suicide (10 cases), heroin injection-related deaths (18 cases), trauma (10 cases), sudden death with minimal coronary atherosclerosis (10 cases), severe coronary atherosclerosis without myocardial infarction (10 cases) and severe coronary atherosclerosis with myocardial infarction (10 cases). Postmortem serum and pericardial fluid β-tryptase levels higher than the clinical reference value (11.4ng/ml) were systematically identified in fatal anaphylaxis following contrast material administration and 6 cases unrelated to anaphylaxis. β-tryptase concentrations in urine and vitreous humor were lower than the clinical reference value in all cases included in this study. Determination of β-tryptase in pericardial fluid appears to be a possible alternative to postmortem serum in the early postmortem period when femoral blood cannot be collected during autopsy and biochemical investigations are required to objectify increased β-tryptase levels.

Exploratory survey about dietary supplement use: a hazardous and erratic way to improve one's health?

INTRODUCTION: Dietary supplement (DS) use increased rapidly in recent years. However, evidence of benefits of many DSs for healthy users is scarce and may not equate with known risks of overdose, drug interaction and recently discovered negative long-term effects. This exploratory study aimed to investigate the perceptions and motivations of DS users in Lausanne, Switzerland. METHOD: A convenience sample (n = 147) was recruited at the entrances of local sales points. Data were collected in on-site semistructured interviews that assessed dietary supplementation habits. RESULTS: The majority of DSs were all-in-one products, containing a mixture of minerals and vitamins, or products containing only minerals. Among the 147 users, 72 (49%) used one all-in-one product and 3 (2%) used two all-in-one products. Thirty-one (21%) consumers did not know for at least one product what the purpose of their DS use was. Seventy-five percent of participants thought that DS use presents no risk or nearly no risk. Only 49% of participants stated that their physicians were informed about their consumption. Although men searched more often for potential risks (p <0.001), they turned less frequently to health professionals to get this information (p = 0.007). DISCUSSION: As in other surveys performed elsewhere, our study shows that, in Lausanne (Switzerland), DSs are commonly used as mixed products. Risk perception seems generally low among DS users. Physicians should be trained to evaluate patients' perceived needs and DS consumption in order to provide good evidence-based information or to propose alternatives to DS use.

Ultra-rapid opiate detoxification using deep sedation and prior oral buprenorphine preparation: long-term results.

BACKGROUND: New methods of ultra-rapid opiate detoxification (URD) under intravenous sedation have been criticized because of limited data on safety and long-term follow-up. Premedication with buprenorphine has been advocated to improve safety by decreasing vomiting. Prior research has not explored URD in socially impaired patients. METHOD: Sixteen patients were detoxified with URD and prospectively evaluated over at least 30 months. Data of this procedure were compared with those of our previous study without buprenorphine preparation (Drug Alcohol Depend. 52(3) (1998) 243). The 16 patients were followed up by a general practitioner (GP) before and after URD. The GPs also supervised the 7-day course of buprenorphine treatment prescribed for the 16 patients prior to URD. RESULTS: During the procedure, only one episode of vomiting occurred instead of 13 out of 20 in our previous study. Post-procedure, only two patients experienced moderate withdrawal symptoms, such as persistent nausea, abdominal cramps and vomiting lasting from 24 to 48 h, in comparison with most patients in the previous study without buprenorphine. After a period of at least 30 months (36.0+/-6.38), the 16 patients were still alive and were regularly monitored by their GP. Only two of the 16 never relapsed after URD and reported total opiate abstinence. Fourteen patients relapsed; 12 of these were prescribed a licensed methadone substitution program and two were still using heroin. CONCLUSION: In this small sample, the data indicated that URD with buprenorphine preparation was safe and that it markedly decreased post-procedure morbidity. No patient died over a minimum 30-month follow-up period. Furthermore, the procedure was employed with socially impaired patients. In the long term, a few patients were still free of opiates, while the majority opted for a methadone maintenance program, showing that URD can serve as one possible step in a long-term treatment program.

Prevalencia de la infección tuberculosa y por el VIH en los usuarios de un programa de reducción de riesgos para usuarios de drogas por vía parenteral (UDVP)

FUNDAMENTO: Determinar la prevalencia de la infección tuberculosa y por el VIH, así como los factores asociados, en la población de usuarios del programa de reducción de riesgos de la ciudad de Lleida. MÉTODOS: La muestra la formaron los nuevos usuarios del programa en el período abril-junio de 1996, entre los los cuales se realizó un cuestionario para la recogida de datos de las variables: edad, sexo, resultado de la prueba de la tuberculina, vacunación BCG, conocimiento de la serología frente al VIH, ingreso en prisión y años de consumo de heroína. Se calculó la prevalencia de la infección tuberculosa y por el VIH, con el intervalo de confianza (IC) del 95%. La asociación de ambas variables con el resto de variables del estudio se determinó mediante la odds ratio (OR) y su IC del 95% . RESULTADOS: Acudieron 150 pacientes diferentes, de los cuales 45 eran nuevos usuarios. De ellos, el 80,0% eran varones, con una edad media de 31,1 años. La prevalencia de la coinfección fue del 8,9% (IC 95% 2,8-22,1). La prevalencia de la infección tuberculosa fue de 27,3% (IC 95% 12,4-43,0), siendo superior en los que tenían antecedentes de ingreso en prisión (OR=3,4; IC 95% 0,5-27,4). La prevalencia de la infección por el VIH fue del 36,1% (IC 95% 21,3-53,8), siendo superior en los que tenían una antigüedad, en el consumo de heroína, superior a los 11 años ( OR = 7,3; IC 95% 1,0-65,9). CONCLUSIONES: El antecedente de ingreso en prisión es el principal factor de riesgo de la infección tuberculosa. Los años de consumo se asocian con la infección por el VIH, especialmente a partir de los 11 años. Los programas de reducción de riesgos de nuestro país deberían realizar actividades de control de la infección tuberculosa y por VIH.

Cannabis use and other illicit drug use: Do subjective experiences during first cannabis use increase the probability of using illicit drug use?

Background and aims: Few studies have examined whether subjective experiences during first cannabis use are related to other illicit drug (OID) use. This study investigated this topic. Methods: Baseline data from a representative sample of young Swiss men was obtained from an ongoing Cohort Study on Substance Use Risk Factors (N ¼ 5753). Logistic regressions were performed to examine the relationships between cannabis use and of subjective experiences during first cannabis use with 15 OID. Results: Positive experiences increased the likelihood of using hallucinogens (hallucinogens, salvia divinorum, spice; p50.015), stimulants (speed, ecstasy, cocaine, amphetamines/methamphetamines; p50.006) and also poppers, research chemicals, GHB/GBL, and crystal meth (p50.049). Sniffed drugs (poppers, solvents for sniffing) and ''hard'' drugs (heroin, ketamine, research chemicals, GHB/GBL and crystal meth) were more likely to be used by participants who experienced negative feelings on first use of cannabis (p50.034). Conclusion: Subjective feelings seemed to amplify the association of cannabis with OID. The risk increased for drugs with effects resembling feelings experienced on first cannabis use. Negative experiences should also be a concern, as they were associated with increased risk of using the ''hardest'' illicit drugs.