Early- and delayed antipsychotic response and prediction of outcome in 528 severely impaired patients with schizophrenia treated with amisulpride

'Early-onset' studies have shown that symptomatic response often occurs early and that early symptomatic response is predictive for later outcome. Limiting factors of these studies include the restriction on symptomatic outcome, the inclusion of mostly moderately ill patients, and the use of various antipsychotics.

The Hamburg-Model of Integrated Care for Patients with Psychosis: Part 1

Objective: The "Hamburg model" designates an integrated care model for severely ill patients with psychotic disorders financed by the health insurance system in accordance with § 140 SGB V.Methods: It comprises comprehensive and long-term treatment within a regional network of the psychosis center of the University Medical Center Hamburg-Eppendorf (UKE) and private psychiatrists. The treatment model consists of therapeutic assertive community treatment (ACT) provided by a highly specialized treatment team and need-adapted in- and outpatient care.Results and conclusions: The present article summarizes the disease- and treatment-specific rationales for the model development as well as the model structure and treatment contents. The article further summarizes the effectiveness and efficiency results of a study comparing the Hamburg model and treatment as usual (without ACT) within a 12-month follow-up study (ACCESS trial).

The Hamburg-Model of Integrated Care for Patients with Psychosis: Part 2

Objective: Since the beginning of the integrated care model for severely ill patients with psychotic disorders ("Hamburg model") in 2007 different clinical parameters have been consecutively assessed within a naturalistic, observational, prospective study.Methods: Clinical outcome of the 2-year and 4-year follow-ups of n = 158 patients.Results: A significant and ongoing improvement of psychopathology, severity of illness, functional outcome, quality of life and satisfaction with care in this sample of severely ill and merely chronic patients with psychosis was shown. Moreover, medication adherence improved and quality and quantity of outpatient treatment increased.Conclusion: The ongoing psychosocial stabilisation of the patients most likely result from a combination of various factors: continuity of care, multimodal and individualized care, therapeutic specialisation and the multidisciplinary ACT team. Results provide clinical and scientific evidence for future implementations of the integrated care model "Hamburg Model" for the treatment of psychosis.

A clinical prediction model to identify patients at high risk of death in the emergency department.

PURPOSE Rapid assessment and intervention is important for the prognosis of acutely ill patients admitted to the emergency department (ED). The aim of this study was to prospectively develop and validate a model predicting the risk of in-hospital death based on all available information available at the time of ED admission and to compare its discriminative performance with a non-systematic risk estimate by the triaging first health-care provider. METHODS Prospective cohort analysis based on a multivariable logistic regression for the probability of death. RESULTS A total of 8,607 consecutive admissions of 7,680 patients admitted to the ED of a tertiary care hospital were analysed. Most frequent APACHE II diagnostic categories at the time of admission were neurological (2,052, 24 %), trauma (1,522, 18 %), infection categories [1,328, 15 %; including sepsis (357, 4.1 %), severe sepsis (249, 2.9 %), septic shock (27, 0.3 %)], cardiovascular (1,022, 12 %), gastrointestinal (848, 10 %) and respiratory (449, 5 %). The predictors of the final model were age, prolonged capillary refill time, blood pressure, mechanical ventilation, oxygen saturation index, Glasgow coma score and APACHE II diagnostic category. The model showed good discriminative ability, with an area under the receiver operating characteristic curve of 0.92 and good internal validity. The model performed significantly better than non-systematic triaging of the patient. CONCLUSIONS The use of the prediction model can facilitate the identification of ED patients with higher mortality risk. The model performs better than a non-systematic assessment and may facilitate more rapid identification and commencement of treatment of patients at risk of an unfavourable outcome.

[Meningitis (II)--acute bacterial meningitis]

Acute meningitis is a medical emergency, particularly in patients with rapidly progressing disease, mental status changes or neurological deficits. The majority of cases of bacterial meningitis are caused by a limited number of species, i.e. Streptococcus pneumoniae, Neisseria meningitis, Listeria monocytogenes, group B Streptococci (Streptococcus agalactiae), Haemophilus influenzae and Enterobacteriaceae. Many other pathogens can occasionally cause bacterial meningitis, often under special clinical circumstances. Treatment of meningitis includes two main goals: Eradication of the infecting organism, and management of CNS and systemic complications. Empiric therapy should be initiated without delay, as the prognosis of the disease depends on the time when therapy is started. One or two blood cultures should be obtained before administering the first antibiotic. Empiric therapy is primarily based on the age of the patient, with modifications if there are positive findings on CSF gram stain or if the patient presents with special risk factors. It is safer to choose regimens with broad coverage, as they can usually be modified within 24-48 hours, when antibiotic sensitivities of the infecting organism become available. Adjunctive therapy with dexamethasone is also administered in severely ill patients concomitantly with the first antibiotic dose. In patients who are clinically stable and are unlikely to be adversely affected if antibiotics are not administered immediately, including those with suspected viral or chronic meningitis, a lumbar puncture represents the first step, unless there is clinical suspicion of an intracerebral mass lesion. Findings in the CSF and on CT scan, if performed, will guide the further diagnostic work-up and therapy in all patients.

A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate

PURPOSE: The primary purpose of the clinical trial was to assess the safety and efficacy of once-a-day compared with three-times-a-day gentamicin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations. PATIENTS AND METHODS: A total of 249 hospitalized patients with suspected or proven serious infections were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC, or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dosage for patients with estimated creatinine clearance values of > or =80 mL/min was 5.1 mg/kg. With lower creatinine clearance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Evaluability required documentation of achievement of protocol-defined peak serum gentamicin levels. RESULTS: Of the total 175 evaluable patients, there were no significant differences found between treatment regimens with respect to clinical or microbiologic efficacy. Bedside audiometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinine values from baseline values, no differences in renal toxicity between the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of renal function, preservation of renal function was better in the gentamicin once-a-day patients as opposed to the gentamicin three-times-a-day patients, P <0.01. CONCLUSIONS: Gentamicin once a day plus TC, gentamicin three times a day plus TC, and TC alone had similar effects in seriously ill hospitalized patients. The incidence of nephrotoxicity was similar in the three treatment groups. Using a nonvalidated post-hoc analysis, renal function was better preserved in gentamicin once-a-day + TC and TC-only patients as opposed to gentamicin three-times-a-day + TC.

Can outcome prediction data change patient outcomes and organizational outcomes?

PURPOSE OF REVIEW: Intensive care medicine consumes a high share of healthcare costs, and there is growing pressure to use the scarce resources efficiently. Accordingly, organizational issues and quality management have become an important focus of interest in recent years. Here, we will review current concepts of how outcome data can be used to identify areas requiring action. RECENT FINDINGS: Using recently established models of outcome assessment, wide variability between individual ICUs is found, both with respect to outcome and resource use. Such variability implies that there are large differences in patient care processes not only within the ICU but also in pre-ICU and post-ICU care. Indeed, measures to improve the patient process in the ICU (including care of the critically ill, patient safety, and management of the ICU) have been presented in a number of recently published papers. SUMMARY: Outcome assessment models provide an important framework for benchmarking. They may help the individual ICU to spot appropriate fields of action, plan and initiate quality improvement projects, and monitor the consequences of such activity.

Once daily dosing of netilmicin in neonatal and pediatric intensive care

OBJECTIVE: To examine a once daily dosing regimen of netilmicin in critically ill neonates and children. DESIGN AND SETTING: Open, prospective study on 81 antibiotic courses in 77 critically ill neonates and children, hospitalized in a multidisciplinary pediatric/neonatal intensive care unit. For combined empiric therapy (aminoglycoside and beta-lactam), netilmicin was given intravenously over 5 min once every 24 h. The dose ranged from 3.5-6 mg/kg, mainly depending upon gestational and postnatal age. Peak levels were determined by immunoassay 30 min after the second dose and trough levels 1 h before the third and fifth dose or after adaptation of dosing. RESULTS: All peak levels (n = 28) were clearly above 12 mumol/l (mean 22, range 13-41 mumol/l). Eighty-nine trough levels were within desired limits (< 4 mumol/l) and 11 (11%) above 4 mumol/l, mostly in conjunction with impaired renal function. CONCLUSIONS: Optimal peak and trough levels of netilmicin can be achieved by once daily dosing, adapted to gestational/postnatal age and renal function.

[Community-integrated acute psychiatric care. Options and limitations]

The shift of psychiatric care from the hospital to the community has been accompanied by a reduction of hospital beds and shortened durations of inpatient treatment, but also by an increase in admissions. This evolution may be largely attributed to the prime focus of community mental health institutions on rehabilitation. The continued implementation of reforms in psychiatric care is contingent upon effectively halting the "revolving door phenomenon" by incorporating community-integrated treatment approaches into the care of acutely ill patients. Since the mid-1960s, a series of studies have established the efficacy of two community-integrated modalities for the treatment of acute psychiatric illness, i.e. home-based and day hospital treatment. In general, these approaches not only seem to be as effective as inpatient care for certain groups of patients but also reduce their need of hospitalisation, thereby contributing towards a cost effective, comprehensive psychiatric care system.

Implantation of the continuous flow HeartWare(R) left ventricular assist device

Recent outstanding clinical advances with new mechanical circulatory systems have led to additional strategies in the treatment of end-stage heart failure. Heart transplantation can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVADs). Mechanical support of the failing left ventricle enables appropriate haemodynamic stabilization and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. An LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group O or B, with high or low body weight and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent perioperative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of an LVAD represents a surgical challenge. The care of patients after the implantation of miniaturized LVADs, such as the HeartWare® system, seems to be easier than following pulsatile devices. The explantation of such devices at the time of transplantation is technically more comfortable than after HeartMate II implantation.

Integrated care programmes for adults with chronic conditions: a meta-review.

OBJECTIVE To review systematic reviews and meta-analyses of integrated care programmes in chronically ill patients, with a focus on methodological quality, elements of integration assessed and effects reported. DESIGN Meta-review of systematic reviews and meta-analyses identified in Medline (1946-March 2012), Embase (1980-March 2012), CINHAL (1981-March 2012) and the Cochrane Library of Systematic Reviews (issue 1, 2012). MAIN OUTCOME MEASURES Methodological quality assessed by the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) checklist; elements of integration assessed using a published list of 10 key principles of integration; effects on patient-centred outcomes, process quality, use of healthcare and costs. RESULTS Twenty-seven systematic reviews were identified; conditions included chronic heart failure (CHF; 12 reviews), diabetes mellitus (DM; seven reviews), chronic obstructive pulmonary disease (COPD; seven reviews) and asthma (five reviews). The median number of AMSTAR checklist items met was five: few reviewers searched for unpublished literature or described the primary studies and interventions in detail. Most reviews covered comprehensive services across the care continuum or standardization of care through inter-professional teams, but organizational culture, governance structure or financial management were rarely assessed. A majority of reviews found beneficial effects of integration, including reduced hospital admissions and re-admissions (in CHF and DM), improved adherence to treatment guidelines (DM, COPD and asthma) or quality of life (DM). Few reviews showed reductions in costs. CONCLUSIONS Systematic reviews of integrated care programmes were of mixed quality, assessed only some components of integration of care, and showed consistent benefits for some outcomes but not others.

Endstation Notfallstation: Perzeption und Rezeption des Begriffs «palliativer Patient» sowie Ansätze zur Verbesserung der interdisziplinären Zusammenarbeit – ein Survey unter notfallmedizinischem Personal auf einer Schweizer Notfallstation

Hintergrund: Wegen sich verändernder Strukturen im Spitalbereich sowie im Bereich der Hausarztabdeckung als auch infolge zunehmenden Drucks auf das Gesundheitssystem kommen mehr Patienten auf die Notfallstationen, die aufgrund ihrer Grunderkrankung und des fortgeschrittenen Krankheitsstadiums von einem palliativen Behandlungskonzept profitieren. Eine wesentliche Herausforderung ist hierbei bereits die Definition von «Palliative Care» (PC), sowie die Klärung, was genau die palliative Versorgung beinhaltet. Häufig vermischt wird der Terminus «Palliative Care» mit «End of life care». Die vorliegende Studie ist eine Standortbestimmung im Universitären Notfallzentrum des Inselspitals Bern (UNZ), das jährlich rund 32 400 Patienten versorgt. Ziel ist es, mehr über den Wissensstand und die persönliche Einstellung der Mitarbeiter zu palliativen Fragestellungen und speziell zum Begriff «Palliative Care» zu erhalten. Methodik: Die Mitarbeiter des Universitären Notfallzentrums des Inselspitals Bern (UNZ) wurden mittels einer Online-Umfrage durch eine spitalexterne Fachinstitution interviewt. Diese Befragung basiert auf einem Instrument [1], das in einer vergleichbaren Studie auf einer Notfallstation in den USA entwickelt und validiert wurde. Resultate: Von 154 Mitarbeitenden (Pflege und Ärzte) füllten 60 Mitarbeitende die Befragung vollständig aus, entsprechend einer Antwortrate von 39%. Die Definition von Palliative Care (von n=60) war sehr heterogen und konnte in sechs Themenbereiche eingeteilt werden. Bei den Fragen nach spezifischen Leistungsangeboten äusserten die Mitarbeitenden den Wunsch nach einem erleichterten Zugang zu bestehenden Patientendaten, nach einem 24-Stunden-Palliative-Care-Konsiliardienst und nach mehr Besprechungszeit für Fragestellungen der PC im klinischen Alltag. Schlussfolgerungen: Die heterogene Begriffsdefinition von «Palliative Care» bestätigt sich. Es besteht kein klares Vorgehen, und zudem lässt sich ein Zeitmangel für ausführliche Patientengespräche in palliativen Situationen im UNZ feststellen. Der Patientenwunsch oder Patientenverfügungen mit DNR/DNI-Prozedere stehen nicht im Widerspruch zu den persönlichen Wertvorstellungen der meisten Mitarbeitenden. Die 24-Stunden-Verfügbarkeit eines spezialisierten PC-Teams, das Erarbeiten von Guidelines und vermehrtes Training für PC würde von den UNZ-Mitarbeitenden begrüsst.

Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe.

The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic "per kg" dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki' disease, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases.

Psychological distress in medical seeking ED care for somatic reasons: results of a systematic review

Objectives: The aim of this systematic literature review is to investigate (A) currently used instruments for assessing psychological distress, (B) the prevalence of psychological distress in medical emergency department (ED) patients with acute somatic conditions and (C) empirical evidence on how predictors are associated with psychological distress. Methods: We conducted an electronic literature search using three databases to identify studies that used validated instruments for detection of psychological distress in adult patients presented to the ED with somatic (non-psychiatric) complaints. From a total of 1688 potential articles, 18 studies were selected for in-depth review. Results: A total of 13 instruments have been applied for assessment of distress including screening questionnaires and briefly structured clinical interviews. Using these instruments, the prevalence of psychological distress detected in medical ED patients was between 4% and 47%. Psychological distress in general and particularly depression and anxiety have been found to be associated with demographic factors (eg, female gender, middle age) and illness-related variables (eg, urgency of triage category). Some studies reported that coexisting psychological distress of medical patients identified in the ED was associated with physical and psychological health status after ED discharge. Importantly, during routine clinical care, only few patients with psychological distress were diagnosed by their treating physicians. Conclusions: There is strong evidence that psychological distress is an important and prevalent cofactor in medically ill patients presenting to the ED with harmful associations with (subjective) health outcomes. To prove causality, future research should investigate whether screening and lowering psychological distress with specific interventions would result in better patient outcomes.

Differential effectiveness of integrated cognitive remediation therapy for schizophrenbia outpatients: The impact oft he duration of illness

Background Nowadays there is extensive evidence available showing the efficacy of cognitive remediation (CR). To date, only limited evidence is available about the impact of the duration of illness on CR effects. The Integrated Neurocognitive Therapy (INT) represents a new developed CR approach. It is a manualized group therapy targeting all 11 NIMH-MATRICS domains. Methods In an international multicenter study, 166 schizophrenia outpatients (DSM-IV-TR) were randomly assigned either to INT or to Treatment-As-Usual (TAU). 60 patients were defined as Early Course group (EC) characterized by less than 5 years of illness, 40 patients were in the Long-Term group (LT) characterized by more than 15 years of illness, and 76 patients were in the Medium-Long-Term group (MLT) characterized by an illness of 5-15 years. Treatment comprised of 15 biweekly sessions. Assessments were conducted before and after treatment and at follow up (1 year). Multivariate General Linear Models (GLM) examined our hypothesis, whether EC, LT, and MLT groups differ under INT and TAU from each other in outcome. Results First of all, the attendance rate of 65% was significantly lower and the drop out rate of 18.5% during therapy was higher in the EC group compared to the other groups. Interaction effects regarding proximal outcome showed that the duration of illness has a strong impact on neurocognitive functioning in speed of processing (F>2.4) and attention (F>2.8). But INT intervention compared to TAU only had a significant effect in more chronically ill patients of MLT and LT, but not in younger patients in EC. In social cognitive domains, only the EC group showed a significant change in attribution (hostility; F>2.5), LT and MLT groups did not. However, no differences between the 3 groups were evident in memory, problem solving, and emotion perception. Regarding more distal outcome, LT patients had more symptoms compared to EC (F>4.4). Finally, EC patients showed higher improvements in psychosocial functioning compared to LT and MLT (F=1.8). Conclusions Against common expectations, long-term, more chronically ill patients showed higher effects in basal cognitive functions compared to younger patients and patients without any active therapy (TAU). On the other hand, early-course patients had a greater potential to change in attribution, symptoms and psychosocial functioning. Consequently, more integrated therapy offers are also recommended for long-term course schizophrenia patients.