Mass Spectrometry for Identification, Monitoring, and Minimal Residual Disease Detection of M-Proteins.

BACKGROUND: Monoclonal gammopathies (MGs) are plasma cell disorders defined by the clonal expansion of plasma cells, resulting in the characteristic excretion of a monoclonal immunoglobulin (M-protein). M-protein detection and quantification are integral parts of the diagnosis and monitoring of MGs. Novel treatment modalities impose new challenges on the traditional electrophoretic and immunochemical methods that are routinely used for M-protein diagnostics, such as interferences from therapeutic monoclonal antibodies and the need for increased analytical sensitivity to measure minimal residual disease. CONTENT: Mass spectrometry (MS) is ideally suited to accurate mass measurements or targeted measurement of unique clonotypic peptide fragments. Based on these features, MS-based methods allow for the analytically sensitive measurement of the patient-specific M-protein. SUMMARY: This review provides a comprehensive overview of the MS methods that have been developed recently to detect, characterize, and quantify M-proteins. The advantages and disadvantages of using these techniques in clinical practice and the impact they will have on the management of patients with MGs are discussed.

[Contact between neighbourhood residents and residents of a residential care facility]. / Contacten van buurtbewoners met bewoners van beschermende woonvormen.

BACKGROUND: Residential care facilities are available to patients unable to live independently, in order to improve their self-reliance and participation. To succeed, integration in the neighbourhood is essential.
AIM: To assess the contact between neighbours and residents of a residential care facility.
METHOD: 364 surveys were distributed in two neighbourhoods with a Yulius residential facility, including questions on frequency and type of contacts, acceptance of psychiatric facilities and of psychiatric patients.
RESULTS: The response rate was 24% (n = 86). Contact with the facility residents was minimal. The experience of nuisance by neighbours was negatively correlated to the acceptance of psychiatric facilities.
CONCLUSION: This limited contact does not point to a successful integration. A more active role of mental health institutions is desired.

[Intensive home treatment: a first observational evaluation]. / Intensive home treatment: een eerste observationele evaluatie.

BACKGROUND: Yulius intensive home treatment (iht) offers six weeks of home-care to psychiatric patients in crisis who would normally be hospitalised.
AIM: To study patient characteristics and the content and outcomes of iht.
METHOD: We followed the handling of 75 consecutive applications for iht. Details were recorded before and after admission to the treatment.
RESULTS: Fifteen patients were referred in order to shorten the period of hospitalisation, and 60 were referred in order to prevent hospitalisation; 59 of the 75 persons admitted for the treatment received iht, and 41 patients finished the six-week module and provided follow-up data. Psychiatric symptoms improved significantly, suicidality was reduced, the caregiver's burden became much lighter and the evaluation by both patient and caregiver was very positive. iht was sufficient to prevent the need for hospitalisation of 75% of the patients referred for reduced hospitalisation, and it was also adequate to prevent the hospitalisation of more than 91% of patients referred for that particular purpose.
CONCLUSION: iht is highly appreciated and is possibly a good alternative to hospitalisation. However, in the future there will have to be randomised, controlled research in order to determine the effectiveness of iht compared to hospitalisation.

Immune involvement in the pathogenesis of schizophrenia: a meta-analysis on postmortem brain studies.

Although the precise pathogenesis of schizophrenia is unknown, genetic, biomarker and imaging studies suggest involvement of the immune system. In this study, we performed a systematic review and meta-analysis of studies investigating factors related to the immune system in postmortem brains of schizophrenia patients and healthy controls. Forty-one studies were included, reporting on 783 patients and 762 controls. We divided these studies into those investigating histological alterations of cellular composition and those assessing molecular parameters; meta-analyses were performed on both categories. Our pooled estimate on cellular level showed a significant increase in the density of microglia (P=0.0028) in the brains of schizophrenia patients compared with controls, albeit with substantial heterogeneity between studies. Meta-regression on brain regions demonstrated this increase was most consistently observed in the temporal cortex. Densities of macroglia (astrocytes and oligodendrocytes) did not differ significantly between schizophrenia patients and healthy controls. The results of postmortem histology are paralleled on the molecular level, where we observed an overall increase in expression of proinflammatory genes on transcript and protein level (P=0.0052) in patients, while anti-inflammatory gene expression levels were not different between schizophrenia and controls. The results of this meta-analysis strengthen the hypothesis that components of the immune system are involved in the pathogenesis of schizophrenia.

[Medication review in the mental health care service: experiences on long-stay units]. / Medicatiebeoordeling in de ggz: praktijkervaring op afdelingen voor langdurig verblijf.

BACKGROUND: Medication review is a recurrent, structured and critical evaluation of pharmacotherapy by patient, physician and pharmacist. The Dutch Health Care Inspectorate considers medication review to be a way of improving the quality and safety of drug treatment. However, little is known about the costs, effectiveness and feasibility of medication review in the practice of mental health care. AIM: To obtain an impression of the costs and benefits of a first medication review in a clinical mental health care setting with chronic patients. METHOD: In 2013, the mental health organisation Yulius enrolled 70 hospitalised chronic patients for a first medication review. A detailed record was kept of the prescribed medication, medication changes, and the time invested. RESULTS: More than half of the proposed changes in medication were eventually implemented; 20% of these changes were made during a planned evaluation after three months. The number of drugs prescribed decreased after medication review; the reduction applied more often to somatic medication than to psychotropic medication. Costs relating to medication reviews seemed to be at least in balance with the benefits. CONCLUSION: In the group of patients with severe mental disorder, medication review seems to provide a good opportunity to assess the rationality of pharmacotherapy in a multidisciplinary approach. The time invested appears to be offset by the benefits of medication review.

The Stability of Comorbid Psychiatric Disorders: A 7 Year Follow Up of Children with Pervasive Developmental Disorder-Not Otherwise Specified.

The current study was a 7-year follow-up of 74 6-12 year old children with Pervasive Developmental Disorder-Not Otherwise Specified. We examined the rates and 7 year stability of comorbid psychiatric diagnoses as ascertained with the Diagnostic Interview Schedule for Children: Parent version at ages 6-12 and again at ages 12-20. Also, we examined childhood factors that predicted the stability of comorbid psychiatric disorders. The rate of comorbid psychiatric disorders dropped significantly from childhood (81 %) to adolescence (61 %). Higher levels of parent reported stereotyped behaviors and reduced social interest in childhood significantly predicted the stability of psychiatric comorbidity. Re-evaluation of psychiatric comorbidity should be considered in clinical practice, since several individuals shifted in comorbid diagnoses.

ASD Symptom Severity in Adolescence of Individuals Diagnosed with PDD-NOS in Childhood: Stability and the Relation with Psychiatric Comorbidity and Societal Participation.

The current 7-year follow-up study investigated: (1) the stability of ASD severity, and (2) associations of ASD severity in adolescence with (a) childhood and concurrent psychiatric comorbidity, and (b) concurrent societal functioning. The Autism Diagnostic Observation Schedule (ADOS) and the Diagnostic Interview Schedule for Children were administered in childhood (ages 6-12) and in adolescence (ages 12-20) to 72 individuals with a pervasive developmental disorder-not otherwise specified (PDD-NOS). ADOS calibrated severity scores showed a large stability (r = .51). Psychiatric comorbidity in childhood and adolescence were not associated with ASD severity in adolescence. Mental health care use (87 %) and special education needs were high (71 %). Reevaluation of ASD severity and psychiatric comorbidity later in life seem useful when PDD-NOS is diagnosed in childhood.

[Contribution to quality of care or caught in a digital labyrinth? Experience with electronic records of patients receiving long-term mental health care]. / Kwaliteitsverbetering of digitaal doolhof? Praktijkervaring met het elektronisch patiëntendossier bij langdurige behandelingen in de ggz.

BACKGROUND: In recent years electronic health records (EHRs) have been introduced on a large scale into mental health care. EHRs have a great number of advantages, one of the main ones being readability. However, very little attention seems to have been paid to the potential disadvantages and risks associated with EHRs. AIM: To point to some of the disadvantages and risks of EHRs, in their present form, particularly in relation to the care of patients with severe mental illness (SMI). METHOD: On the basis of clinical experience and relevant literature, we discuss some of the disadvantages and risks associated with EHRs in their current form. RESULTS: In long-term, multidisciplinary and complex treatments of patients with SMI, EHRs in their current form fail to provide the psychiatrist with an adequate overview of the treatment process. This is largely due to the way they are designed: an ever-increasing quantity of information about complex treatment stored in separate files that can only be accessed individually and that contain free text. In mental health care the introduction of new technology, unlike the introduction of new drugs, seems to occur without structured surveillance of the disadvantages and risks involved. CONCLUSION: EHRs need to be re-designed at the earliest opportunity.

[Addition of fluvoxamine to clozapine: theory and practice]. / Additie van fluvoxamine aan clozapine: theorie en praktijk.

BACKGROUND: The addition of fluvoxamine to clozapine induces a rise of plasma concentrations of clozapine. This enables the prescription of a lower number of clozapine tablets, yet it attains sufficient clozapine plasma concentrations, and facilitates treatment adherence. AIM: Providing practical advice for the practical implementation of the addition of fluvoxamine to clozapine. METHOD: A review of the literature with Ovid Medline and the presentation of a case series (N=7). RESULTS: Addition of 25 or 50 mg fluvoxamine induces a mean rise of plasma concentrations of clozapine with a factor 2-3, probably even higher with the addition of 100 mg. However, the range of this factor varies considerably between individuals. The use of clozapine and fluvoxamine at the same time possibly has a favourable impact on the metabolic side-effects of clozapine. CONCLUSION: Addition of fluvoxamine to clozapine can lead to a dangerous rise of clozapine plasma concentrations. However, it can also be used to prescribe a lower number of clozapine tablets and to facilitate treatment adherence. A sufficient safety margin should be taken and regular control of clozapine plasma concentrations is mandatory.

[Recognition of psychiatric disorders with a religious content by members of the clergy of different denominations in the Netherlands]. / De herkenning van psychische problemen met religieuze inhoud door pastores: een vignetstudie.

BACKGROUND: Clergy members (CMS) frequently provide support and counselling for people with psychological and psychiatric disorders. There is evidence in the literature that CMS consider themselves to be inadequately trained to recognise psychiatric disorders. AIM: To investigate to what extent CMS are able to recognise psychiatric symptoms. METHOD: CMS were recruited in the south-west of the Netherlands among various denominations (Roman Catholic, strict (orthodox) Protestant, moderate Protestant and Evangelical; n = 143) by means of a regional sampling method. The participating CMS (n = 143) and a control group consisting of mental health care professionals MPHS; n = 73) evaluated four vignettes of psychiatric problems with a religious content: two were about a psychiatric disorder (a psychotic state and a psychotic depression/melancholic state), and two concerned non-psychiatric states (a spiritual/religious experience and a mourning reaction with a religious dilemma). For each vignette the respondents scored the suitability of psychiatric medication, the desirability of mental health care, the severity of the disorder and whether there was a religious or spiritual aetiology. RESULTS: Some CMS were able to recognise psychiatric problems almost as well as the MHPS, but among the CMS the degree of recognition varied according to the denomination. Recognition was relatively poor among Evangelical CMS, but was best among the strict Protestant CMS. Evangelical pastors and strict Protestant CMS tended to interpret the non-psychiatric states as pathological. CONCLUSION: The findings of this study emphasise the need for collaboration between MHPS and CMS and stress the importance of consultation.

Psychiatric side effects and fluctuations in serotonergic parameters in the treatment of chronic hepatitis C infection.

INTRODUCTION: Treatment of hepatitis C with peginterferon induces psychiatric side effects. These might include changes in serotonergic function. METHODS: Twenty-two hepatitis C patients were treated with peginterferon. At different time points, psychometric assessment was performed using the profile of mood states. Plasma samples were taken to study serotonergic parameters. RESULTS: Anger and depression increased compared to baseline, starting with anger (from week 3 onwards), followed by depression (from week 7 onwards). Other scores did not show consistent changes. No consistent changes were observed in tryptophan, tryptophan/large neutral amino acids ratio, biopterin and 5-hydroxyindoleacetic acid. The tyrosine/large neutral amino acids ratio, neopterin, phenylalanine/tyrosine ratio, and prolactin concentrations increased compared to baseline. Prolactin levels were associated with the occurrence of depression and anger. DISCUSSION: Particularly anger and depression increased during treatment. Neither a decrease in tryptophan and tryptophan availability was seen, nor a relationship between these parameters and the development of psychopathology. Therefore, other mechanisms in the induction of psychopathology should be considered. The observed increases in neopterin and phenylalanine/tyrosine ratio are indicative of changes in tetrahydrobiopterin, which is involved in the metabolism of serotonin, noradrenaline and dopamine, and possibly mediating the increase in prolactin. The increase in prolactin levels and its relationship with depression and anger needs further exploration.

The effects of guided discontinuation of antipsychotics on neurocognition in first onset psychosis.

OBJECTIVE: To assess the effects of second generation antipsychotics on neurocognitive function in patients with stable remission of first episode psychosis. METHODS: Fifty-three patients with first onset psychosis in the schizophrenia spectrum entered a randomised controlled trial of guided discontinuation (GD) versus maintenance treatment (MT) with second generation antipsychotics. A comprehensive neurocognitive test battery was administered at the time of remission and shortly after dose reduction or discontinuation (GD-group) or at the same time in the MT-group. RESULTS: With the exception of negative symptoms, PANSS scores decreased over time and neurocognition improved significantly on most tests in both groups. The GD-group, however, improved significantly more than the MT-group on three neurocognitive measures in the domain of speed of processing. CONCLUSION: These data suggest that, in first episode patients, dose reduction or discontinuation of second generation antipsychotics after stable remission is achieved, might improve neurocognitive function more than continuing second generation antipsychotics, suggesting a negative role for second generation antipsychotics, specifically in the domain of speed of processing.

Randomised clinical trial: escitalopram for the prevention of psychiatric adverse events during treatment with peginterferon-alfa-2a and ribavirin for chronic hepatitis C.

BACKGROUND Treatment of hepatitis C with peginterferon and ribavirin is associated with psychiatric side-effects, frequently necessitating dose reduction or therapy cessation. AIM To assess the efficacy of prophylactic escitalopram to prevent psychiatric side-effects during peginterferon and ribavirin treatment in a randomised, double-blind, placebo-controlled trial. METHODS Seventy-nine hepatitis C patients were treated with peginterferon and ribavirin. Patients received escitalopram (n = 40, 10 mg) or placebo (n = 39), which was initiated together with peginterferon and ribavirin. Primary outcomes were an increase of two points or more on the items reported sadness, inner tension and impaired concentration of the Montgomery-Asberg Depression Rating Scale, and hostile feelings of the Brief Anxiety Scale. Secondary outcome was the development of depression diagnosed by the Mini-International Neuropsychiatric Interview. Measurements were performed at baseline, week 4, 12 and 24 during anti-viral treatment, and 24 weeks thereafter. RESULTS The incidence of psychiatric side-effects was significantly lower in patients treated with escitalopram compared with placebo for all primary and secondary outcomes, except for impaired concentration: reported sadness 27.5 vs. 48.7% (P = 0.052), inner tension 17.5 vs. 38.5% (P = 0.038), impaired concentration 55.0 vs. 66.7% (P = 0.288) and hostile feelings 22.5 vs. 43.6% (P = 0.046) (escitalopram vs. placebo, Chi-squared test). The sum scores of all four endpoints showed an overall beneficial effect of escitalopram (P = 0.009, Mann-Whitney U-test). Depression occurred in 12.5% of the patients in the escitalopram-group vs. 35.9% in the placebo-group (P = 0.015, Chi-squared test). CONCLUSIONS Prophylactic treatment with escitalopram is effective in the prevention of psychiatric side-effects during interferon-based treatment of hepatitis C.

[Typical and atypical antipsychotics: Is there a difference in their influence on neurocognition?]. / Typische en atypische antipsychotica bij patiënten met schizofrenie: is er verschil in invloed op neurocognitie?

BACKGROUND: Neurocognitive dysfunction is a core feature of schizophrenia and is related to the functional outcome of the illness. It has been suggested that the so-called atypical antipsychotics may have a more favourable influence on neurocognition than the older, typical antipsychotics and thus also on the functional outcome. AIM: To review the recent scientific literature concerning the effects of antipsychotics on neurocognition. METHOD: The literature was reviewed systematically via the most important databases. RESULTS: Meta-analyses suggest that atypical antipsychotics have moderate, positive effects on neurocognition and in that respect are more beneficial than typical antipsychotics. Recent studies, however, challenge this finding. CONCLUSION: The reported positive, cognitive effects of atypical antipsychotics are slight, particularly compared to the severity of neurocognitive dysfunction found in schizophrenia. In clinical practice there seem to be no convincing reason for attaching much weight to any differential effects that typical or atypical antipsychotics may have on neurocognition.

[Toxic plasma concentration of clozapine in inflammatory processes]. / Toxische plasmaconcentratie van clozapine bij ontstekingsprocessen.

Clozapine has a narrow therapeutic range. The threshold value for plasma concentrations is 350 µg/l. If plasma concentrations exceed that value, serious side-effects can occur. An increase in plasma concentrations can occur as a result of inflammatory processes which may or may not be caused by an infection. Two cases are discussed in which the plasma concentration of clozapine increased as a result of an inflammatory reaction and signs of intoxication were observed. These developments seemed to be due to cholecystitis and bacterial pneumonia respectively. The clinical presentation and pathophysiology are discussed in relation to inflammatory processes.

[Antipsychotic agents and stimulants: a judicious combination?]. / Antipsychotica en stimulantia: een zinvolle combinatie?

A 31-year-old male, diagnosed with schizophrenia and receiving maintenance treatment with olanzapine, was prescribed methylphenidate for comorbid attention deficit hyperactivity disorder (adhd). The adhd symptoms diminished and there were hardly any side-effects. No increase in psychotic symptoms occurred. The patient used far fewer amphetamines and benzodiazepines. In theory, stimulants and antipsychotics produce opposite effects. Relevant literature on the subject is discussed.

[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.

Plasma activity of prolyl endopeptidase in relation to psychopathology during immunotherapy with IFN-alpha in patients with renal cell carcinoma.

Abnormal activity in peripheral blood of the cytosolic enzyme prolyl endopeptidase (PEP, EC 3.4.21.26, post prolyl cleaving enzyme, prolyl oligopeptidase) has been found in patients with a variety of psychiatric disorders, most consistently in mood disorders. Mood disturbance is a well-known side effect of immunotherapy with interferon-alpha (IFN-alpha). Earlier, we documented a decrease in serum PEP activity in the first 4 weeks of treatment with IFN-alpha. In 24 patients (16 men, 8 women, median age 60.5 years, range 47-72 years) with metastatic renal cell carcinoma (RCC), psychiatric assessment and blood sampling were performed before and at 4 and 8 weeks and at 6 months after initiation of treatment with IFN-alpha. No episodes of depression were observed, and the sum score and the scores on the subscales for depression and hostility of the Symptom Check List-90 (SCL-90) did not change during follow-up, whereas the anxiety scores were somewhat lower at 4 and 8 weeks compared with baseline. No change in plasma PEP activity and no relationships between change in psychiatric parameters and change in plasma PEP activity were found. As more subtle relationships between PEP activity and psychiatric status could have easily been obscured, a role for PEP in the pathophysiology of IFN-alpha-induced mood disturbance can neither be confirmed nor excluded.