The Obesity Paradox in the Trauma Patient: Normal May not Be Better.

OBJECTIVE: The obesity paradox is the association of increased survival for overweight and obese patients compared to normal and underweight patients, despite an increased risk of morbidity. The obesity paradox has been demonstrated in many disease states but has yet to be studied in trauma. The objective of this study is to elucidate the presence of the obesity paradox in trauma patients by evaluating the association between BMI and outcomes. METHODS: Using the 2014-2015 National Trauma Database (NTDB), adults were categorized by WHO BMI category. Logistic regression was used to assess the odds of mortality associated with each category, adjusting for statistically significant covariables. Length of stay (LOS), ICU LOS and ventilator days were also analyzed, adjusting for statistically significant covariables. RESULTS: A total of 415,807 patients were identified. Underweight patients had increased odds of mortality (OR 1.378, p < 0.001 95% CI 1.252-1.514), while being overweight had a protective effect (OR 0.916, p = 0.002 95% CI 0.867-0.968). Class I obesity was not associated with increased mortality compared to normal weight (OR 1.013, p = 0.707 95% CI 0.946-1.085). Class II and Class III obesity were associated with increased mortality risk (Class II OR 1.178, p = 0.001 95% CI 1.069-1.299; Class III OR 1.515, p < 0.001 95% CI 1.368-1.677). Hospital and ICU LOS increased with each successive increase in BMI category above normal weight. Obesity was associated with increased ventilator days; Class I obese patients had a 22% increase in ventilator days (IRR 1.217 95% CI 1.171-1.263), and Class III obese patients had a 54% increase (IRR 1.536 95% CI 1.450-1.627). CONCLUSION: The obesity paradox exists in trauma patients. Further investigation is needed to elucidate what specific phenotypic aspects confer this benefit and how these can enhance patient care. LEVEL OF EVIDENCE: Level III, prognostic study.

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

[Pharmacotherapy of psychiatric acute and emergency situations: General principles]. / Pharmakotherapie von psychiatrischen Akut- und Notfallsituationen : Allgemeine Prinzipien.

The pharmacotherapy of psychiatric emergencies is essentially determined by the acuteness, the scene of the emergency, the diagnostic assessment and the special pharmacological profile of the drug used. As there are no specific drugs, syndromic treatment is carried out. For this, primarily antipsychotic drugs and benzodiazepines are available. This article gives an overview of the current state of treatment options for major psychiatric emergency syndromes, namely agitation, delirium, stupor and catatonia, anxiety and panic, as well as drug-induced emergencies.

[Psychiatric care in emergency departments]. / Psychiatrische Versorgung in der Notaufnahme.

BACKGROUND: Psychiatric emergency situations (PES) are frequent in emergency departments (EDs). There are, however, only few investigations that focus on the prevalence of these patients or on diagnostic and therapeutic standards. These PESs in EDs should be treated according to standards comparable to medically disabled patients. Thus it is necessary to learn more about the diagnostic and therapeutic possibilities in EDs, about the procedures and the decision-making process whether these patients are transferred to further outpatient or inpatient treatment. MATERIALS AND METHODS: A survey was conducted in EDs throughout Germany and 1,073 were contacted and asked to participate. The questionnaire consisted of questions concerning the size of the ED and of the hospital (e.g. number of patients and physicians), the prevalence of psychiatric disorders, the diagnostic and therapeutic possibilities, standard procedures for dealing with PES and the method of care in six typical case reports. RESULTS: A total of 74 EDs participated (76% interdisciplinary EDs) with an average of 22,827 ± 12,303 patients per year in the ED. Psychiatry as a medical discipline was integrated into 10 EDs (14%) and psychiatric competence could be activated in 84% of EDs. Participating EDs reported prevalence rates of 15% mentally disordered patients and 9% of patients who required psychiatric diagnostic and therapeutic procedures. Of the patients 2% presented after suicide attempts and 3% were considered to be aggressive. Approximately 50% of all PESs were related to substance abuse disorders. An average of 2.5 ± 4.2 (range 0-25) members of the medical and nursing staff were injured during a 1-year period by violent patients. Legal actions against the will of patients were initiated in 81% of EDs. Standardized diagnostic screening instruments or self-rating questionnaires were used in only four EDs. As standard procedures for the diagnostic work-up of psychiatric patients (medical clearance) physical examination, measurement of heart rate and blood pressure and conducting of some laboratory tests (glucose, blood cell count, electrolytes and renal function) were named. Diazepam (91%), lorazepam (88%) and haloperidol (87%) were considered to be indispensable psychopharmacological agents in the ED. CONCLUSIONS: In the majority of participating EDs, diagnostic standards for PES were known but were not routinely applied. It has to be assumed that many psychiatric disorders, in particular suicide attempts and suicidal ideation are not discovered. In many EDs psychiatric knowledge was available but a psychiatric consultation was only rarely requested. Physicians in the ED report a high degree of legal uncertainty with psychiatric patients. The use of screening instruments is recommended.

Effects of polypharmacy on outcome in patients with schizophrenia in routine psychiatric treatment.

OBJECTIVE: Evaluating the effects of different types of psychotropic polypharmacy on clinical outcomes and quality of life (QOL) in 374 patients with schizophrenia and schizoaffective disorder in routine care. METHOD: Psychotropic regimen, clinical outcomes, and QOL were assessed before discharge and after 6, 12, 18, and 24 months. Data were analyzed by mixed-effects regression models for longitudinal data controlling for selection bias by means of propensity scores. RESULTS: At baseline 22% of participants received antipsychotic monotherapy (APM) (quetiapine, olanzapine, or risperidone), 20% more than one antipsychotic drug, 16% received antipsychotics combined with antidepressants, 16% antipsychotics plus benzodiazepines, 11.5% had antipsychotics and mood stabilizers, and 16% psychotropic drugs from three or more subclasses. Patients receiving APM had better clinical characteristics and QOL at baseline. Patients receiving i) antipsychotics plus benzodiazepines or ii) antipsychotics plus drugs from at least two additional psychotropic drug categories improved less than patients with APM. CONCLUSION: Combinations of antipsychotics with other psychotropic drugs seem to be effective in special indications. Nevertheless, combinations with benzodiazepines and with compounds from multiple drug classes should be critically reviewed. It is unclear whether poorer outcomes in patients with such treatment are its result or its cause.

AGNP consensus guidelines for therapeutic drug monitoring in psychiatry: update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint eff ort.

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from "strongly recommended" to "potentially useful". Evidence-based "therapeutic reference ranges" and "dose related reference ranges" were elaborated after an extensive literature search and a structured internal review process. A "laboratory alert level" was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.

Response and remission of subjective well-being in patients suffering from schizophrenia spectrum disorders.

BACKGROUND: Purpose of this study was to assess subjective well-being in schizophrenia inpatients and to find variables predictive for response and remission of subjective well-being. METHOD: The subjective well-being under neuroleptic treatment scale (SWN-K) was used in 232 schizophrenia patients within a naturalistic multicenter trial. Early response was defined as a SWN-K total score improvement of 20% and by at least 10 points within the first 2 treatment weeks, response as an improvement in SWN-K total score of at least 20% and by at least 10 points from admission to discharge and remission in subjective well-being as a total score of more or equal to 80 points at discharge. Logistic regression and CART analyses were used to determine valid predictors of subjective well-being outcome. RESULTS: Twenty-nine percent of the patients were detected to be SWN-K early responders, 40% fulfilled criteria for response in subjective well-being and 66% fulfilled criteria for remission concerning subjective well-being. Among the investigated predictors, SWN-K early improvement and the educational status were significantly associated with SWN-K response. The SWN-K total score at baseline showed a significant negative predictive value for response. Baseline SWN-K total score, PANSS global subscore, and side effects as well as the educational status were found to be significantly predictive for remission. CONCLUSIONS: Depressive symptoms should be radically treated and side effects closely monitored to improve the patient's subjective well-being. The important influence of subjective well-being on overall treatment outcome could be underlined.

Evaluating depressive symptoms and their impact on outcome in schizophrenia applying the Calgary Depression Scale.

OBJECTIVE: To examine depressive symptoms, their course during treatment, and influence on outcome. METHOD: Weekly Calgary Depression Scale for Schizophrenia ratings were performed in 249 inpatients with schizophrenia. Early response was defined as a 20% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia from admission to week 2, response as a 50% reduction in the total score of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS) from admission to discharge and remission according to the consensus criteria. RESULTS: Thirty six per cent of the patients were depressed at admission, with 23% of them still being depressed at discharge. Depressed patients scored significantly higher on the PANSS negative and general psychopathology subscore, featured more impairments in subjective well-being (P < 0.0001) and functioning (P < 0.0001). They suffered from more suicidality (P = 0.0021), and had greater insight into their illness (P = 0.0105). No significant differences were found regarding early response, response, and remission. CONCLUSION: Patients with depressive symptoms should be monitored closely, given the burden of negative symptoms, their impairments in well-being and functioning and the threat of suicidality.

A critical analysis and discussion of the appropriateness of the schizophrenia consensus remission criteria in clinical pharmaceutical trials.

BACKGROUND: The aim of this paper is to apply the proposed consensus remission criteria to an acutely ill inpatient sample at admission and evaluate their adaptability in this patient population and pharmaceutical trials. METHODS: The Remission in Schizophrenia Working Group's consensus criteria were applied to 272 acutely ill schizophrenia patients. Patients were examined using the PANSS, HAMD, UKU and SWN-K total scales at admission as well as the GAF, SOFAS and the Strauss-Carpenter Prognostic Scale. Sociodemographic and clinical baseline variables were assessed using a standardized documentation system. RESULTS: 33 patients (12%) fulfilled the symptom severity component of the proposed remission criteria already at baseline. Almost no significant differences were found when comparing patients with achieved and failed symptom severity component that would explain the hospitalization of the patients with achieved criteria despite their apparently mild psychopathological symptoms. The only explainable difference was that patients with an achieved symptom severity component had received significantly more antipsychotics and had suffered from significantly more life events before admission. CONCLUSION: The present results raise the question whether the symptom severity threshold is adequate to identify patients in remission when applied in clinical trials.

Time course of antipsychotic treatment response in schizophrenia: results from a naturalistic study in 280 patients.

OBJECTIVE: To describe the course of positive and negative symptoms during inpatient treatment and examine remission and response rates under routine clinical care conditions. METHODS: Two hundred and eighty inpatients with schizophrenia (DSM-IV criteria) were assessed with the Positive and Negative Syndrome Scale (PANSS) at admission and at biweekly intervals until discharge from hospital. Remission was defined according to the symptom-severity component of the consensus criteria (Remission in Schizophrenia Working Group) as a rating of three or less in the relevant PANSS items at discharge, and response as a reduction of at least 20% in the PANSS total score from admission to discharge. RESULTS: The mean duration of inpatient treatment was 54.8 days. Of the total sample, 78.5% achieved the criteria for response and 44.6% those for remission. Mean PANSS total scores decreased from 72.4 at admission to 52.5 at discharge (p<0.001). A reduction in PANSS total scores was found from visit to visit, up to week 8. The most pronounced decline was observed within the first two weeks of treatment. CONCLUSION: Response rates were comparable to those found in efficacy studies, and remission rates were slightly higher. This may be explained by differences in the selection and the treatment of patients. Nevertheless, the findings might indicate that a complex naturalistic treatment approach is beneficial in terms of effectiveness.

[Combining antidepressants: a useful strategy for therapy resistant depression?]. / Kombination von Antidepressiva--eine sinnvolle Behandlungsstrategie bei therapieresistenten Depressionen?

Various pharmacological strategies have been developed to treat such refractory depression, of which combination therapies with antidepressants are one of the most important. This article reviews both benefits and risks of all known antidepressant combination strategies. The relevant literature was identified by means of a computerized MEDLINE research on the years 1990-2006 and scanning of review articles. The use of antidepressant combinations to overcome refractory depression is a common strategy in practice. Many antidepressants can be usefully combined especially if they engage separate mechanisms of action--like SSRIs with Reboxetine, Bupropion, Mirtazapine and Tricyclics--or on the other hand--Tricyclics with MAO-Inhibitiors. Combination strategies are effective treatment options, however they do have potential safety risks due to pharmacokinetic and pharmacodynamic interactions. Combinations including MAOIs can cause serotonin syndrome, and some SSRIs like Fluoxetine may elevate tricyclic plasma levels with the consequence of an increased risk of toxicity. The distinct knowledge of available antidepressant combination strategies may help to increase response--as well as remission rates in therapy resistant depression. However, further research is urgently needed to determine relative efficacy.

Long-term treatment with flupentixol results of a post-marketing surveillance study.

Schizophrenia is one of the most expensive illnesses. Antipsychotics are an essential component of the acute and preventative treatment of this illness, and long-term treatment is necessary to decrease the risk of psychotic relapse. The efficacy and tolerability of flupentixol was evaluated in a post-marketing surveillance study (PMS) in schizophrenic patients receiving long-term treatment in routine clinical practice. Psychiatrists in office practice treated patients for approximately 10 weeks, with a subsequent follow-up period of up to 18 months. We here report on the follow-up period in 128 patients. The benefit for schizophrenic patients increased with the treatment duration of flupentixol as documented by the Clinical Global Impression (CGI). Subjective quality of life improved during the first study period, and this remained stable in the follow-up period. No increase in body weight was observed during the study. The relapse rate was much lower than in other studies. Anticholinergic medication was necessary for 22.7% of the patients at any time. More than 70% of the psychiatrists involved evaluated the treatment as very good or good. The results of this study suggest that flupentixol is a potent and safe antipsychotic for the long-term treatment of schizophrenia in routine clinical practice.

Standardized remission criteria in schizophrenia: descriptive validity and comparability with previously used outcome measures.

INTRODUCTION: Standardized consensus criteria for remission in schizophrenia were recently proposed. As yet, the validity of these criteria and their comparability with previously used outcome measures are unclear. METHODS: The symptom-severity component of the proposed remission criteria was applied to 288 inpatients who fulfilled the ICD-10 criteria for schizophrenia. Global functioning and psychopathological symptoms were assessed using GAF, PANSS, SANS, HAM-D and CDSS. RESULTS: When patients with symptom remission at discharge from hospitalization (n=158, 54.9%) were compared to those without symptom remission, significant differences were found with respect to the global functioning (GAF) and all observed psychopathological symptom dimensions. The percentage agreement with previously used outcome measures ranged between 52.6 and 80.0%, the kappa values between 0.120 and 0.594. A moderate accordance (kappa value: 0.495) was found with a Clinical Global Impression (CGI) severity score of three or less. DISCUSSION: The results indicate a high descriptive validity of the symptom-severity component of the proposed remission definition. However, the new criteria differ partially from previously used outcome measures. This aspect should be considered in the interpretation of clinical trials.

[Polypharmacy in the treatment of schizophrenia]. / Polypharmazie in der Behandlung der Schizophrenie.

Current standards for the pharmacological treatment of schizophrenia favour antipsychotic monotherapy. Most atypical antipsychotics developed in recent years meet the statutory requirement of being at least as effective as Haloperidol. Nevertheless, pharmacoepidemiological data show an increase in polypharmacy. The importance of the studies is underlined by the fact that 40 - 50 % of schizophrenic inpatients and up to 90 % schizophrenic outpatients receive antipsychotic combination therapies. Treatment resistance, reduction of dose-related side effects caused by antipsychotic monotherapy or the effect on concomitant symptoms of schizophrenia, such as comorbid depression, might justify combination therapy or augmentation strategies. Apart from the high costs, polypharmacy is associated with reduced patient compliance and an increased risk of undesired pharmacological effects. Since polypharmacy is increasingly common further educational measures in psychopharmacology should be getting more attention. Due to the very small number of controlled studies that exist at present this report will focus on case reports of the most frequent as well as some of the lesser prescribed combination therapies. Finally, conclusions will be discussed in relation to therapy recommendations.