High pneumococcal DNA load, procalcitonin and suPAR levels correlate to severe disease development in patients with pneumococcal pneumonia.

Community-acquired pneumonia (CAP) is mostly caused by Streptococcus pneumoniae. Identification of the pathogen causing CAP can be achieved by conventional culture techniques of sputum and/or blood, antigen detection from urine or molecular analysis. However, it remains difficult to determine patients who are at risk of severe disease development (intensive care unit [ICU] admittance and/or death). In this retrospective study, 121 patients admitted to the emergency department with pneumonia symptoms were included. Several markers of infection (pneumococcal DNA load in blood (real-time LytA PCR), white blood cell (WBC) count, C-reactive protein (CRP), procalcitonin (PCT) and soluble urokinase plasminogen activator receptor (suPAR) levels) were assessed for their ability to predict severe disease development. Of 121 patients, 6 were excluded from the study because of an alternative diagnosis, whereas 8 were excluded from biomarker analysis because of the presence of co-morbidities. Of the 115 patients analysed by the LytA PCR, 23 were positive. PCR detected S. pneumoniae DNA in 82% of patients with positive blood culture for S. pneumoniae. PCR missed three samples from patients in which S. pneumoniae was recovered by blood cultures. However, eight additional LytA PCR-positive samples were detected from patients whose blood cultures remained negative. Pneumococcal DNA load was also monitored in time for 31 patients, of whom 11 had positive PCR results. For 10 out of 11 (91%) positive PCR patients, a clear increase in Ct-values was observed, indicating a lower pneumococcal DNA load in the blood as a result of antibiotic therapy. Biomarker analysis was performed in 107 patients, of whom 29 showed severe disease development. Pneumococcal DNA load (p = 0.026), PCT (p = 0.046) and suPAR (p = 0.001) levels most reliably predicted severe disease development. In conclusion, in patients with CAP, higher pneumococcal DNA load, PCT and suPAR values are associated with severe disease development (ICU admission and/or death). These biomarkers may be useful tools for triage of patients suspected of having CAP in the emergency department.

Practical recommendations for improvement of the physical health care of patients with severe mental illness.

OBJECTIVE: Health care for the physical health of patients with severe mental illness (SMI) needs to be improved. Therefore, we aimed to develop policy recommendations to improve this physical health care in the Netherlands based on consensus (general agreement) between the major stakeholders. METHOD: A modified Delphi was used to explore barriers and subsequently establish policy recommendations with all key stakeholders. Consensus was sought between patients with SMI, their family carers, general practitioners, and mental healthcare professionals--all experts in the everyday practice of health care. RESULTS: Consensus was reached on policy recommendations regarding (i) improvements in collaboration between healthcare professionals, (ii) the need for professional education on the specific medical risks of patients with SMI, and (iii) the distinguished responsibilities of general practitioners on the one hand and mental healthcare professionals on the other hand in taking care of patients' physical health. CONCLUSION: This article provides a range of policy recommendations that could lead to considerable improvements in the physical health of SMI patients.

Developments for improved diagnosis of bacterial bloodstream infections.

Bloodstream infections (BSIs) are associated with high mortality and increased healthcare costs. Optimal management of BSI depends on several factors including recognition of the disease, laboratory tests and treatment. Rapid and accurate identification of the etiologic agent is crucial to be able to initiate pathogen specific antibiotic therapy and decrease mortality rates. Furthermore, appropriate treatment might slow down the emergence of antibiotic resistant strains. Culture-based methods are still considered to be the "gold standard" for the detection and identification of pathogens causing BSI. Positive blood cultures are used for Gram-staining. Subsequently, positive blood culture material is subcultured on solid media, and (semi-automated) biochemical testing is performed for species identification. Finally, a complete antibiotic susceptibility profile can be provided based on cultured colonies, which allows the start of pathogen-tailored antibiotic therapy. This conventional workflow is extremely time-consuming and can take up to several days. Furthermore, fastidious and slow-growing microorganisms, as well as antibiotic pre-treated samples can lead to false-negative results. The main aim of this review is to present different strategies to improve the conventional laboratory diagnostic steps for BSI. These approaches include protein-based (MALDI-TOF mass spectrometry) and nucleic acid-based (polymerase chain reaction [PCR]) identification from subculture, blood cultures, and whole blood to decrease time to results. Pathogen enrichment and DNA isolation methods, to enable optimal pathogen DNA recovery from whole blood, are described. In addition, the use of biomarkers as patient pre-selection tools for molecular assays are discussed.

[Hidden diseases: tuberculosis in a woman with a severe mental illness]. / Tbc bij een vrouw met een ernstige psychiatrische aandoening.

Patients with severe mental illness often have only limited access to health care for physical symptoms. They have difficulty in organising their thoughts and articulating their requests for medical help; in addition, they often have a reduced perception of stimuli like physical pain. There may also be a language barrier and sometimes a cultural barrier. The case that we present demonstrates that these are not separate causes but they are interrelated in a complex manner. Screening for a latent disease such as tuberculosis reduces the risk of a delayed diagnosis stemming from the patient's inability to articulate a request for medical help. The physical symptoms of patients with severe mental illness can only be reliably interpreted when there is close cooperation between physicians and psychiatrists.

Evaluating interventions to improve somatic health in severe mental illness: a systematic review.

OBJECTIVE: To present a systematic review of the evaluation of randomized interventions directed toward improving somatic health for patients with severe mental illness (SMI). METHOD: A systematic search in PubMed, Embase, Cinahl, and PsycInfo was performed. The scope of the search was prospective studies for patients aged 18-70, published from January 2000 till June 2011. Randomized interventions directed toward improving somatic health for patients with SMI were selected. We excluded studies on elderly, children, and studies performed before 2000. Information on population, type of intervention, follow-up, outcome measures, and on authors' conclusions were drawn from the original articles. RESULTS: Twenty-two original studies were included, presenting four types of interventions: health education (n = 9), exercise (n = 6), smoking cessation (n = 5), and changes in health care organization (n = 2). To evaluate the effect of these studies 93 different outcome measures were used in 16 categories. CONCLUSION: Many interventions directed toward improving somatic health for patients with SMI have been started. These studies did not apply similar evaluations, and did not use uniform outcome measures of the effect of their interventions. Valuable comparisons on effectiveness are therefore almost impossible.

Influencing CYP enzymes to boost psychiatric treatment: a review on clinical evidence.

INTRODUCTION: Therapeutic drug monitoring to optimize blood plasma concentrations is advised for certain psychiatric drugs. The current standard is to change the dose based on the blood plasma concentration. We present an overview that blood plasma concentrations can also be influenced by adding co-medication based on pharmacokinetic knowledge. METHOD: We performed a systematic review in medical databases for pharmaco-enhancing strategies, and we present 2 cases on actively influencing CYP3A4 metabolism. RESULTS: 4 original studies were selected on strategies to influence CYP metabolism. 2 studies on influencing CYP2D6 metabolism, 2 studies on influencing CYP1A2 metabolism. In all studies an effect of this influence was present.Ample clinical evidence is present, but shows promising results. Pharmacokinetic knowledge can and should be used in clinical settings to optimize pharmacotherapy for vulnerable patients. Also the access to expensive medication can be increased by reduction of high dosage schemes.

An evaluation of three processing methods and the effect of reduced culture times for faster direct identification of pathogens from BacT/ALERT blood cultures by MALDI-TOF MS.

Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) is a fast and reliable method for the identification of bacteria from agar media. Direct identification from positive blood cultures should decrease the time to obtaining the result. In this study, three different processing methods for the rapid direct identification of bacteria from positive blood culture bottles were compared. In total, 101 positive aerobe BacT/ALERT bottles were included in this study. Aliquots from all bottles were used for three bacterial processing methods, i.e. the commercially available Bruker's MALDI Sepsityper kit, the commercially available Molzym's MolYsis Basic5 kit and a centrifugation/washing method. In addition, the best method was used to evaluate the possibility of MALDI application after a reduced incubation time of 7 h of Staphylococcus aureus- and Escherichia coli-spiked (1,000, 100 and 10 colony-forming units [CFU]) aerobe BacT/ALERT blood cultures. Sixty-six (65%), 51 (50.5%) and 79 (78%) bottles were identified correctly at the species level when the centrifugation/washing method, MolYsis Basic 5 and Sepsityper were used, respectively. Incorrect identification was obtained in 35 (35%), 50 (49.5%) and 22 (22%) bottles, respectively. Gram-positive cocci were correctly identified in 33/52 (64%) of the cases. However, Gram-negative rods showed a correct identification in 45/47 (96%) of all bottles when the Sepsityper kit was used. Seven hours of pre-incubation of S. aureus- and E. coli-spiked aerobe BacT/ALERT blood cultures never resulted in reliable identification with MALDI-TOF MS. Sepsityper is superior for the direct identification of microorganisms from aerobe BacT/ALERT bottles. Gram-negative pathogens show better results compared to Gram-positive bacteria. Reduced incubation followed by MALDI-TOF MS did not result in faster reliable identification.

[Psychotropic drugs dispensed on the island of Bonaire]. / Psychofarmacaverstrekkingen op Bonaire.

BACKGROUND: Up till now little is known about psychiatric disorders in relation to the use of psychotropics drugs on the Dutch Antilles, with the exception of Curaçao. AIM: To map the quantity and type of psychotropics prescribed for Bonairians in 2009. METHOD: We performed a retrospective data analysis of the antipsychotics dispensed by the pharmacies on Bonaire in 2009. Our analysis focused on the benzodiazepines and related compounds, antipsychotics, lithium, antidepressants and ADHD- and narcolepsy-medication. With regard to antipsychotics and antidepressants, we also investigated 'the age distribution of the persons to whom the psychotropics were dispensed'. In addition, we mapped the frequency with which the drugs were dispensed: once only, infrequently, regularly. RESULTS: At least one psychotropic drug was delivered to 18.37% of (N=2365) Bonairians in 2009. Benzodiazepines and related compounds in particular were the most commonly dispensed drugs. CONCLUSION: One in five Bonairians received at least one prescription for psychotropic drugs in 2009.

Acceleration of the direct identification of Staphylococcus aureus versus coagulase-negative staphylococci from blood culture material: a comparison of six bacterial DNA extraction methods.

To accelerate differentiation between Staphylococcus aureus and coagulase-negative staphylococci (CNS), this study aimed to compare six different DNA extraction methods from two commonly used blood culture materials, i.e. BACTEC and BacT/ALERT. Furthermore, we analysed the effect of reduced blood culture incubation for the detection of staphylococci directly from blood culture material. A real-time polymerase chain reaction (PCR) duplex assay was used to compare the six different DNA isolation protocols on two different blood culture systems. Negative blood culture material was spiked with methicillin-resistant S. aureus (MRSA). Bacterial DNA was isolated with automated extractor easyMAG (three protocols), automated extractor MagNA Pure LC (LC Microbiology Kit M(Grade)), a manual kit MolYsis Plus and a combination of MolYsis Plus and the easyMAG. The most optimal isolation method was used to evaluate reduced bacterial incubation times. Bacterial DNA isolation with the MolYsis Plus kit in combination with the specific B protocol on the easyMAG resulted in the most sensitive detection of S. aureus, with a detection limit of 10 CFU/ml, in BacT/ALERT material, whereas using BACTEC resulted in a detection limit of 100 CFU/ml. An initial S. aureus or CNS load of 1 CFU/ml blood can be detected after 5 h of incubation in BacT/ALERT 3D by combining the sensitive isolation method and the tuf LightCycler assay.

Substantial skin disorders in psychiatric illness coincide with diabetes and addiction.

BACKGROUND: Dermatological diseases in psychiatric patients are common; however, epidemiological data on this subject are scarce and to our knowledge integral studies of dermatological disease in psychiatric inpatients are not available yet. AIM: The aim of this study was to describe the incidence of dermatological problems in psychiatric inpatients. METHOD: This study evaluates the consultations for new dermatological problems by inpatients of a general psychiatric hospital of over 700 beds during a 6-month period. RESULTS: A total of 255 patients consulted their physician because of a new dermatological problem. Diagnoses (n=360) included skin infections (32%), accidents (7%), decubitus ulcers (7%), complications of medical treatment (3%), auto mutilation (1%) and neoplasms of the skin (1%). Patients with skin infections were likely to have diabetes [odds ratio (OR)=3.6; 95% confidence interval (CI): 1.56-8.40]. Patients with decubitus ulcers were likely to have an addiction problem (OR=6.4; 95% CI: 1.46-28.00). Dermatitis was associated with affective disorder (OR=2.5; 95% CI: 1.12-5.43) but not with psychosis (OR=0.5; 95% CI: 0.23-0.90). Only a poor correlation existed between the length of hospital stay and skin problems. CONCLUSIONS: Dermatological problems are common in hospitalized psychiatric patients. Patients with diabetes mellitus are at high risk for skin infections. There are significant relationships between the psychiatric and the dermatological diagnoses. The length of the admission to a psychiatric hospital does not seem to play a major role in skin diseases.

Treatment adherence therapy in people with psychotic disorders: randomised controlled trial.

BACKGROUND: Interventions to improve adherence to treatment in people with psychotic disorders have produced inconclusive results. We developed a new treatment, treatment adherence therapy (TAT), whose intervention modules are tailored to the reasons for an individual's non-adherence. AIMS: To examine the effectiveness of TAT with regard to service engagement and medication adherence in out-patients with psychotic disorders who engage poorly. METHOD: Randomised controlled study of TAT v. treatment as usual (TAU) in 109 out-patients. Most outcome measurements were performed by masked assessors. We used intention-to-treat multivariate analyses (Dutch Trial Registry: NTR1159). RESULTS: Treatment adherence therapy v. TAU significantly benefited service engagement (Cohen's d = 0.48) and medication adherence (Cohen's d = 0.43). Results remained significant at 6-month follow-up for medication adherence. Near-significant effects were also found regarding involuntary readmissions (1.9% v. 11.8%, P = 0.053). Symptoms and quality of life did not improve. CONCLUSIONS: Treatment adherence therapy helps improve engagement and adherence, and may prevent involuntary admission.

Missense polymorphisms in three oxidative-stress enzymes (GSTP1, SOD2, and GPX1) and dyskinesias in Russian psychiatric inpatients from Siberia.

Neuronal degeneration due to oxidative stress (OS) has been proposed as a mechanism for tardive dyskinesia (TD) pathogenesis. Cellular defense mechanisms against OS may involve detoxification enzymes (e.g., glutathione peroxidase-1, GPX1; superoxide dismutase-2, SOD2 [also commonly known as MnSOD]; and glutathione S-transferase P1, GSTP1). Several pharmacogenetic studies have examined TD and OS in different ethnic groups, but not in Russians. Here we report the association between orofaciolingual (TDof) and limb-truncal dyskinesias (TDlt) and polymorphisms of GSTP1 (Ile105Val), MnSOD (Ala-9Val), and GPX1 (Pro197Leu) genes in 146 Russian inpatients from Siberia. We applied AIMS instrument to rate dyskinesias. Two-part model analyses, logistic and multivariate parametric regressions were applied to assess the effects of different variables (e.g., genotype, age, gender, and medication use). Our analyses do not suggest that Pro197Leu (GPX1) is associated with TD. However, our analyses suggest that the 105Val-allele of Ile105Val (GSTP1) may be associated with a lower risk and a severity of TDof and TDlt and that Ile105Val pharmacogenetics may be different in Slavonic Caucasians from that in American Caucasians. Furthermore, we find evidence for an association between Ala-9Val (MnSOD) and TDof, but not TDlt. Subject to further replication, our findings extend the available knowledge on the pharmacogenetics of TD and oxidative stress.

Skin disorders in chronic psychiatric illness.

BACKGROUND: Chronic psychiatric patients are prone to develop skin diseases. However, epidemiological data are scarce. OBJECTIVE: To describe the prevalence of skin complaints and dermatological disorders in residential psychiatric patients. METHODS: Ninety-one randomly chosen patients of the residential wards of a general psychiatric hospital completed a short, structured interview concerning skin disease and underwent a physical examination of the skin. RESULTS: Of the examined patients, 69% reported symptoms of skin disease in the month prior to the interview and 77% had skin disorders at physical examination. In 34 (37%) patients, skin disorders were diagnosed, which were not mentioned in the interview. Patients with diabetes had infectious skin disease more often than their fellow patients [odds ratio (OR) 10.9; 95% confidence interval (CI): 2.40-49.75]. Moreover, overweight patients had infectious skin disease more often (OR 7.4; 95% CI: 1.38-39.3). Women reported more skin complaints (OR 6.4: 95% CI: 1.67-24.2), and also had skin problems other than infection, tumours or dermatitis more frequently (OR 3.7; 95% CI: 1.34-10.14). Clozapine use was associated with benign neoplasms of the skin. The nature of this association remains unclear and merits further investigation. CONCLUSIONS: Many chronic psychiatric patients have skin problems. Clinical examination of the skin is important to discover these problems. Patients with diabetes mellitus are particularly at risk for skin infections. Because of their relationship with overweight and diabetes mellitus, atypical antipsychotics may be partly responsible for these serious complications. Only a few other relationships between psychiatric medication and specific skin problems were found.

Diagnose, indicate, and treat severe mental illness (DITSMI) as appropriate care: A three-year follow-up study in long-term residential psychiatric patients on the effects of re-diagnosis on medication prescription, patient functioning, and hospital bed utilization.

BACKGROUND: While polypharmacy is common in long-term residential psychiatric patients, prescription combinations may, from an evidence-based perspective, be irrational. Potentially, many psychiatric patients are treated on the basis of a poor diagnosis. We therefore evaluated the DITSMI model (i.e., Diagnose, Indicate, and Treat Severe Mental Illness), an intervention that involves diagnosis (or re-diagnosis) and appropriate treatment for severely mentally ill long-term residential psychiatric patients. Our main objective was to determine whether DITSMI affected changes over time regarding diagnoses, pharmacological treatment, psychosocial functioning, and bed utilization. METHODS: DITSMI was implemented in a consecutive patient sample of 94 long-term residential psychiatric patients during a longitudinal cohort study without a control group. The cohort was followed for three calendar years. Data were extracted from electronic medical charts. As well as diagnoses, medication use and current mental status, we assessed psychosocial functioning using the Health of the Nations Outcome Scale (HoNOS). Bed utilization was assessed according to length of stay (LOS). Change was analyzed by comparing proportions of these data and testing them with chi-square calculations. We compared the numbers of diagnoses and medication changes, the proportions of HoNOS scores below cut-off, and the proportions of LOS before and after provision of the protocol. RESULTS: Implementation of the DITSMI model was followed by different diagnoses in 49% of patients, different medication in 67%, some improvement in psychosocial functioning, and a 40% decrease in bed utilization. CONCLUSIONS: Our results suggest that DITSMI can be recommended as an appropriate care for all long-term residential psychiatric patients.

Tardive dyskinesia and DRD3, HTR2A and HTR2C gene polymorphisms in Russian psychiatric inpatients from Siberia.

BACKGROUND: Pharmacogenetics of tardive dyskinesia and dopamine D3 (DRD3), serotonin 2A (HTR2A), and 2C (HTR2C) receptors has been examined in various populations, but not in Russians. PURPOSE: To investigate the association between orofaciolingual (TDof) and limb-truncal dyskinesias (TDlt) and Ser9Gly (DRD3), -1438G>A (HTR2A), and Cys23Ser (HTR2C) polymorphisms in Russian psychiatric inpatients from Tomsk, Siberia. METHODS: In total, 146 subjects were included. Standard protocols were applied for genotyping. TDof and TDlt were assessed with AIMS items 1-4 and 5-7, respectively. Two-part model, logistic and log-normal regression analyses were applied to assess different variables (e.g., allele-carriership status, age, gender, and medication use). RESULTS: TDlt, but not TDof, exhibited an association with Ser9Gly and Cys23Ser (with 9Gly and 23Ser alleles exhibiting opposite effects). However, -1438G>A was not associated with TDof and Dlt. CONCLUSIONS: This is the first pharmacogenetic report on tardive dyskinesia in Russians. Subject to further replication, our findings extend and support the available data.

A cross-sectional study of prescribing patterns in chronic psychiatric patients living in sheltered housing facilities.

OBJECTIVE: To analyze prescribing patterns of chronic psychiatric patients living in sheltered housing facilities, to identify the extent of polypharmacy and to estimate associated risks in this patient group. METHODS: In a retrospective cross-sectional study the prescription data of 323 chronic psychiatric patients (average age 48.5 years) living in sheltered housing facilities in Rotterdam, The Netherlands, were analyzed. Prescription data were obtained from pharmacy-dispensing records. RESULTS: Patients received on average 4.6 drugs (95% CI, 4.3-4.9). The most frequently prescribed drugs were as expected antipsychotics, benzodiazepines and antimuscarinic drugs. Overall 25% (n=81) of patients received two or more antipsychotic drugs. A high proportion of patients (38%, n=124) received one benzodiazepine, and 15% (n=50) received two or more benzodiazepines. CONCLUSION: Patients in our study received a worryingly high number of drugs, and a quarter of the population was subject to antipsychotic polypharmacy. This increases the risk that drug-drug interactions, adverse drug reactions and noncompliance occur. Our study indicates potentially low quality of prescribing and shows the need for reviewing and special monitoring of pharmacotherapy in this patient group.

[Schizophrenia and antipsychotics associated with the metabolic syndrome. An overview]. / Schizofrenie en antipsychotica: samenhang met het metabool syndroom.

BACKGROUND: Cardiovascular morbidity and mortality are higher in patients with schizophrenia than in the general population because the metabolic side-effects of antipsychotics and schizophrenia increase the risk of cardiovascular disease (cvd) and diabetes mellitus type 2 (DM2). The metabolic syndrome is defined in order to discover which patients have a high risk of developing cvd and DM2. AIM: To survey the current knowledge about the relationship between schizophrenia and the metabolic syndrome, the influence of the use of antipsychotics on the development of the metabolic syndrome, and the possible differences in the effects that first and second generation antipsychotics have on the syndrome. METHOD: The PubMed and Medscape databases were searched for relevant articles published between 2000 and July 2008. results Schizophrenia and the use of antipsychotics increase the prevalence of abdominal obesity, dyslipidemia and DM2 (i.e. the metabole syndrome). Second generation antipsychotics tend to cause a marked increase in the prevalence of abdominal obesity and dyslipidemia, whereas first generation antipsychotics hardly have any of these effects. Both first and second generation antipsychotics increase the risk of DM2. CONCLUSION: The metabolic syndrome has a significant effect on the morbidity and mortality of patients with schizophrenia because it increases the risk they will develop cvd and DM2. The risk increases still further if patients are taking antipsychotics. The risk of cvd can be decreased if patients with schizophrenia are screened in time and are monitored regularly.

[Chemotherapy during clozapine treatment. Increased risk of agranulocytosis?]. / Chemotherapie bij gebruik van clozapine; een verhoogde kans op agranulocytose?

In a 37-year-old female, a combined treatment consisting of chemotherapy and radiation was considered for cervical cancer. However, she was using clozapine for the treatment of schizophrenia. As both clozapine and chemotherapy can induce decrease of white blood cell counts, we had to decide if clozapine and chemotherapy could be safely co-prescribed. Hypotheses concerning the mechanisms underlying clozapine-induced decrease of white blood cell counts and case reports on combining chemotherapy and clozapine are discussed. After cessation of clozapine the psychosis recurred despite treatment with risperidone. The decision was made to administer radiotherapy only and to reinstate the treatment with clozapine. The radiotherapy treatment went according to plan and the psychosis receded.