Antipsychotic drug-induced neutropenia: results from the AMSP drug surveillance program between 1993 and 2016.

Neutropenia and agranulocytosis (N&A) are relatively rare, but potentially fatal adverse drug reactions (ADR). This study presents cases of N&A related to one or more antipsychotic drugs (APDs) in psychiatric inpatients. Data on APD utilization and reports of N&A caused by APDs were analyzed by using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2016. 333,175 psychiatric inpatients were treated with APDs for schizophrenia and other indications during the observation period. A total of 124 cases of APD-induced N&A were documented, 48 of which fulfilled the criteria for agranulocytosis, corresponding to a rate of 0.37, respectively, 0.14 in 1000 inpatients treated with APDs. Neutropenia was more often detected in women, whereas there was no difference regarding sex in cases of agranulocytosis. Clozapine had the highest relative risk for inducing N&A and was imputed alone as a probable cause of N&A in 60 cases (1.57‰ of all patients exposed). Perazine showed the second highest relative risk with 8 cases and an incidence 0.52‰, followed by quetiapine (15 cases resp. 0.23‰ of all patients exposed) and olanzapine (7 cases; 0.13‰ of all patients exposed). N&A most often occurred during the first 3 months of treatment. Overall N&A are severe and potentially fatal complications that can occur during treatment with APDs. The results from this study largely agree with the currently available literature, highlighting the positive effects of alertness and established appropriate monitoring.

Incidence of Drug-Induced Delirium During Treatment With Antidepressants or Antipsychotics: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2016.

OBJECTIVES: Successful treatment of delirium depends on the detection of the reversible contributors. Drugs with delirogenic properties are the most prevalent reversible cause of delirium. METHODS: This observational study is based on data from Arzneimittelsicherheit in der Psychiatrie, a multicenter drug surveillance program in German-speaking countries recording severe adverse drug reactions (ADRs) in psychiatric inpatients. The present study analyzes drug-induced delirium (DID) during treatment with antidepressants and antipsychotics. RESULTS: A total of 436 565 psychiatric inpatients were treated with antidepressants and/or antipsychotics during the observation period from 1993 to 2016 in the participating 110 hospitals. Overall, 254 cases (0.06% of all patients treated with antidepressants and/or antipsychotics) of DID were detected. Implicated either in combination or alone (multiple drugs were implicated in 70.1% of DID), clomipramine (0.24%), amitriptyline (0.21%), and clozapine (0.18%) showed the highest incidence rates of DID. When implicated alone (98 cases overall), clozapine (0.11%) followed by amitriptyline (0.05%) were most likely causally associated with the occurrence of DID. Drugs with strong antimuscarinic properties generally exhibited higher risk of DID. CONCLUSIONS: With an incidence rate of <0.1%, the use of antidepressants and antipsychotics was rarely associated with DID within the Arzneimittelsicherheit in der Psychiatrie program. Tricyclic antidepressants and clozapine were the most commonly implicated psychotropic drugs. These data support the specific role of antimuscarinic properties in DID.

Galactorrhea during antipsychotic treatment: results from AMSP, a drug surveillance program, between 1993 and 2015.

Galactorrhea is a well-known adverse drug reaction (ADR) of numerous antipsychotic drugs (APD) and is often distressing for those affected. Methodological problems in the existing literature make it difficult to determine the prevalence of symptomatic hyperprolactinemia in persons treated with APDs. Consequently, a large sample of patients exposed to APDs is needed for more extensive evaluation. Data on APD utilization and reports of galactorrhea caused by APDs were analyzed using data from an observational pharmacovigilance program in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP)-from 1993 to 2015. 320,383 patients (175,884 female inpatients) under surveillance were treated with APDs for schizophrenia and other indications. A total of 170 events of galactorrhea caused by APDs were identified (0.97 cases in 1000 female inpatient admissions). Most cases occurred during the reproductive age with the highest incidence among patients between 16 and 30 years (3.81 cases in 1000 inpatients). The APDs that were most frequently imputed alone for inducing galactorrhea were risperidone (52 cases and 0.19% of all exposed inpatients), amisulpride (30 resp. 0.48%), and olanzapine (13 resp. 0.05%). In three cases, quetiapine had a prominent role as a probable cause for galactorrhea. High dosages of the imputed APDs correlated with higher rates of galactorrhea. Galactorrhea is a severe and underestimated condition in psychopharmacology. While some APDs are more likely to cause galactorrhea, we identified a few unusual cases. This highlights the importance of alertness in clinical practice and of taking a patient's individual situation into consideration.

[First Results of the German consulting center for infection control outbreak registry]. / Infektionen und Kolonisationen: Was können wir verbessern?

BACKGROUND: Outbreaks of infectious diseases and / or colonization pose an increasing burden on hospitals and the health system in general and can be a threat to patient safety. METHODS: At the end of 2013 we implemented a quality assurance registry of outbreak investigations performed by the Deutsches Beratungszentrum für Hygiene (German Consulting Center for Infection Control and prevention) in Freiburg. Now we analyzed the registered outbreaks until January 2015. RESULTS: Norovirus was the leading causative organism and gram negative bacteria dominated the group of bacterial outbreaks. Outbreaks lasted between 6 and 185 days. 24 % of outbreaks were related to colonization only. Within 29 outbreaks we had 187 infected patients, 50 colonized patients und 92 infected health care workers (64 x norovirus, 20 x influenza, 8 x scabies). No deaths were recorded. Several risk factors and improvement potentials for future outbreaks could be identified. CONCLUSION: Lack of staff compliance with vaccination or prophylactic therapy, misuse of personal protective equipment and lapses in absence from work for the required time can play an important role for prolonged outbreak situations esp. with viral outbreaks and scabies. A structured and goal directed outbreak management especially in the initial phase of an outbreak seems to be important for an efficient and fast termination of an outbreak.

[Colonization-outbreak of two clonally different strains of Serratia marcescens in a neonatal intensive care unit]. / Kolonisationsausbruch mit zwei klonal unterschiedlichen Stämmen von Serratia marcescens auf einer neonatologischen Intensivstation.

We describe an outbreak of two clonally different strains of Serratia marcescens in a neonatal intensive care unit. Three colonization cases in the first outbreak phase were related to contact transmission from an index patient during emergency respiratory treatment while eight colonizations in the second phase were caused by contaminated bathing lotion. All transmissions resulted in colonization only and no infections were recorded. Based on our experience and the literature review sufficient staffing levels, basic hygiene and a goal-directed investigation of the environment are the cornerstones of a rapid outbreak termination. The epidemiological search for parallels in cases should be assisted by sophisticated electronic records.

History, background, concepts and current use of comedication and polypharmacy in psychiatry.

Based on a careful literature search a review is presented of the history, background, concepts and current use of comedication and polypharmacy in psychiatry. The pros and cons of comedication and polypharmacy are presented, as well as their apparent increase in recent times. Possible reasons for the increase of comedication/polypharmacy are described. Both the potential advantages as well as the potential risks are discussed. The one sided view that all comedication/polypharmacy is nothing but problematic is questioned. Comedication/polypharmacy seems to be, among others, the current answer to the well-known limited efficacy and effectiveness of current monotherapy treatment strategies.

Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study.

This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice.

[Infection prevention by the anesthesia team]. / Infektionsprävention durch das anästhesieteam.

The anesthesia team acts every day in a highly complex and high risk environment for the transmission of pathogenic organisms and the induction of infectious complications. With strict adherence to standard precautions and infection control practices in particular regular hand disinfection before and after direct patient contact and before performance of aseptic tasks during anesthesia and an optimized perioperative process the members of the anesthesia team can become infection control pioneers within the hospital. In order to be successful, structural and organizational resources in the form of training, personnel, materials and time, need to be adequate for the situation. This review summarizes the infection control recommendations for anesthesia practice based on the most recent literature and guidelines and offers practical advice for commonly observed mistakes.

[Quality management in regional anesthesia using the example of a Regional Anesthesia Surveillance System (RASS)]. / Qualitätsmanagement in der Regionalanästhesie am Beispiel des Regionalanästhesie Surveillance Systems (RASS).

Regional anesthesia and regional analgesia techniques with or without a continuous catheter are frequently utilized in all areas of modern anesthesiology. There are individual and economic benefits but also risks involved with those techniques. While the incidence of severe complications is rare and preventive action not always possible, the consequences can be detrimental especially with hematoma or abscess formation associated with central neuraxial blocks. Therefore, it is important to create national and international databases with large case numbers utilizing standardized definitions of complications in order to allow realistic risk assessment and early discovery of potential dangers and preventive actions. This article shows the integration of standardized codes from the Regional Anesthesia Surveillance System with a software tool to allow high-quality data acquisition and the building of a foundation for national and international data collection and analysis as well as for feedback of institutional data for individual process optimization as part of a quality management system.

Tight turns in stick insects.

We investigated insects Carausius morosus walking whilst hanging upside down along a narrow 3 mm horizontal beam. At the end of the beam, the animal takes a 180 degrees turn. This is a difficult situation because substrate area is small and moves relative to the body during the turn. We investigated how leg movements are organised during this turn. A non-contact of either front leg appears to indicate the end of the beam. However, a turn can only begin if the hind legs stand in an appropriate position relative to each other; the outer hind leg must not be placed posterior to the inner hind leg. When starting the turn, both front legs are lifted and usually held in a relatively stable position and then the inner middle leg performs a swing-and-search movement: The leg begins a swing, which is continued by a searching movement to the side and to the rear, and eventually grasps the beam. At the same time the body is turned usually being supported by the outer middle leg and both hind legs. Then front legs followed by the outer middle leg reach the beam. A scheme describing the turns based on a few simple behavioural elements is proposed.

Nosocomial infections and infection control in regional anesthesia.

BACKGROUND: Although rare, infectious complications from regional anesthesia and analgesia can be devastating. The literature on this topic consists primarily of surveys, case reports, case series, and studies in which used supplies were cultured. We derived infection control recommendations from the existing literature and compared these recommendations with existing guidelines. METHODS: Structured literature search of the Cochrane Central Register of Controlled Trials, MEDLINE, including old MEDLINE and EMBASE until 2005. Descriptive statistics were cited when applicable. MAIN RESULTS: Incidence rates for infectious complications vary substantially between studies and range from 3.7 to 7.2/100,000 for spinal anesthesia-associated meningitis and from 0.2 to 83/100,000 for epidural anesthesia-associated epidural abscesses. Few comprehensive prospective trials have been conducted and most case reports do not provide complete information about infection control practices. CONCLUSION: Studies using more robust methods are necessary to define the rates of infection after different regional anesthesia procedures and to identify risk factors for infections. Data on risk factors would allow anesthesiologists to develop evidence-based guidelines for placement and care of catheters used for regional anesthesia. A multicenter surveillance system may help anesthesiologists address some of the unanswered questions and to develop evidence-based infection control recommendations.

[Sadistic fetishism--deadly passion. Forensic psychiatric assessment of sex offenders]. / Tödliche Lust--sadistischer Fetischismus. Forensisch-psychiatrische Begutachtung von Sexualstraftätern.

This article reviews current developments in psychiatric assessment of sex offenders for criminal courts. These developments are characterized by constantly changing laws and increasing neurobiological findings about paraphilias. Psychiatrists must prepare their reports taking into account the tension between psychopathological, neurobiological, and normative aspects of their judgement. The complexity of such assessments can best be demonstrated by narratives. This narrative concerns a 47-year-old patient who killed eight women after strangling them and masturbating or having intercourse with the unconscious victims. He explained in detail six of these crimes and gave ample information about his history, sexual development, fantasies, and a number of other sexual crimes he had committed. From this information a plausible explanation of his development to sexual fetishism and from there to sadism could be derived. Brain MRI displayed gliotic scars in the frontal lobe and right hippocampus. Consequences of the various findings on psychiatric assessment of legal culpability are discussed in this paper, concluding that a differentiated approach to the assessment is possible only from a psychopathological point of view in which behaviour, clinical features, and motivations are analysed.

Regional Anesthesia Surveillance System: first experiences with a quality assessment tool for regional anesthesia and analgesia.

BACKGROUND: The incidence of complications related to regional anesthesia and analgesia is hardly known and estimates are based on extrapolation from controlled trials, insurance registries and retrospective chart reviews and only a few attempts of prospective data collection have been made. We designed a surveillance system for regional anesthesia for easy and reliable data acquisition. METHODS: A list of definitions of complications and quality indicators of interest was created and introduced in a single institution. Data are collected within the hospital information system and by individual reports of complications from trained reporters in the Acute Pain Service. A data cross-check is performed by the Surveillance coordinator. RESULTS: We present complications rates for 9790 catheter days and 4547 punctures for continuous neuraxial and peripheral nerve blocks between October 2003 and January 2006. Most complications were related to catheter dislocation and 'wet taps'. Serious complications such as neurologic deficits, bleeding complications and infections were rare. Data quality reached 98% reliability of complication coding. DISCUSSION: This is the description of a prospective regional anesthesia surveillance system, which currently allows longitudinal analysis of performance parameters at a single institution and will provide data about the incidences of complications related to regional anesthesia and analgesia in the future.

[Safety and effectiveness of the cervical paravertebral approach to the brachial plexus--data from the Regional Anesthesia Surveillance System (RASS)]. / Sicherheit und Effektivität des zervikal posterioren Zugangs zum Plexus brachialis--Daten des Regionalanästhesie Surveillance Systems (RASS).

BACKGROUND: This is the first report of the Regional Anesthesia Surveillance System (RASS) analyzing complication data of the relatively new cervical posterior approach to the brachial plexus. MATERIAL AND METHODS: The Regional Anesthesia Surveillance System (RASS) was introduced in October 2003. All regional anesthesia punctures and continuous catheters in place are recorded as part of the midnight-statistic and forwarded to the RASS databank. Complications are registered and coded according to standardized definitions ( www.UIRASS.com ) by the acute pain service. Plausibility of coding is checked against the medical record by the RASS-coordinator for data quality assurance. RESULTS: From October 2003-October 2005 there have been 360 cervical posterior punctures and 547 catheterdays. The utilization ratio of the cervical posterior brachial plexus block is 1.42 %. A pneumothorax occurred in 2.7/1000 punctures, local anesthetic toxicity and short term neurologic deficits were also observed in 2.7/1000 punctures. Catheter dislocation occurred in 5.4/1000 catheterdays and severe neck pain was noticed in 16.3/1000 punctures. There were no catheter associated long term neurological deficits, bleeding or infectious complications. CONCLUSION: The cervical posterior approach to the brachial plexus is an alternative to the interscalene approach with the advantages of high success rate and secure catheter placement. Neck pain can be a disadvantage of the technique and acute complications like pneumothorax and local anesthetic toxicity seem to be similar to those reported with interscalene blocks in the literature.