[Analysis of mental health care utilization data in comparison with medical-specialist and general practitioner health care consumption data]. / Behoefte aan en consumptie van ggz-zorg vergeleken met somatische zorg in Nederland.

BACKGROUND: Quantification of population-level socioeconomic-demographic factors impacting onset and course of health care consumption can help health care commissioning and public health planning.
AIM: To analyse associations between mental health care, medical-specialist care and general practitioner (GP) care with regional socioeconomic-demographic factors. Two cost parameters were examined: (i) absolute costs; and (ii) relative costs, defined as the proportion of PC3-level costs attributable to outliers (defined as costs above the 80th percentile - as a proxy for care intensity).
METHOD: Analysis of Vektis data over the period 2014-2017 in the age range of 18-65 years.
RESULTS: Mental health care cost variation was for 28% reducible to (younger) age, urbanicity, PC3-level ethnic density and PC3-level socioeconomic-demographic factors. Variation in medical-specialist care and GP care costs were reducible principally to (older) age. Costs attributable to outliers ranged from 34% for GP care to 55% for mental health care. Socioeconomic-demographic factors explained a substantial part of the variation in the PC3-level proportion of outlier costs for mental health care (31%), medical-specialist care (43%) and GP-care (33%).
CONCLUSION: Analysis of the degree and pattern of socioeconomic-demographic factors impacting mental health care can inform both public mental health planning and mental health care commissioning. Tijdschrift voor psychiatrie 63(2021)1, 39-47.

Clinical effects and treatment outcomes of long-term compulsory in-patient treatment of treatment-resistant patients with severe mental illness and substance-use disorder.

BACKGROUND: The treatment of homeless dual-diagnosis patients (i.e., those with severe mental illness and substance-use disorder) is difficult and often fails. For patients in the Netherlands who had not responded to earlier voluntary and compulsory treatment, a new treatment facility - Sustainable Residence (SuRe) - was developed to offer long-term compulsory in-patient treatment. AIM OF THE STUDY: To study patterns of changes in clinical and functional outcomes during treatment at SuRe and how these relate to eventual treatment outcome. METHODS: On the basis of the intensity of care needed after four years, three groups of patients were distinguished (total n = 165): those discharged to a less restrictive and less supportive setting (n = 70, 42%), those still hospitalized at SuRe at the end of the four-year study period (n = 69, 42%) and those referred to a more appropriate setting (n = 26, 16%). Random coefficient analysis was used to examine differences between groups regarding changes in clinical and functional outcomes during treatment. During treatment, outcomes were monitored using Routine Outcome Assessment. RESULTS: All three groups made small but significant improvements on global psychosocial functioning, distress and therapeutic alliance (effect sizes (ES) 0.11 to 0.16 per year). Patients who were discharged to a less restrictive setting showed small to moderate improvement in risk to self and others, psychiatric symptoms, and skills for daily living (ES 0.19-0.33 per year and 0.42-0.73 for their mean 2.2-year treatment period). Patients remaining at SuRe showed a small increase in risk to self (ES 0.20 per year; 0.80 for their treatment period of four years or more). Oppositional behaviour was consistently greater in referred patients than in the other groups (ES 0.74-0.75). CONCLUSION: Long-term compulsory treatment appeared to have helped improve clinical and functional outcomes in a substantial proportion (42%) of previously severely dysfunctional, treatment-resistant dual-diagnosis patients, who could then be discharged to a less restrictive and less supportive environment. However, risk-to-self increased in a similar proportion. A smaller number of patients (16%) showed marked oppositional behaviour and needed a higher level of care and protection in another facility.

The use of an electronic clinical rule to discontinue chronically used benzodiazepines and related Z drugs.

PURPOSE: The chronic use of benzodiazepines and benzodiazepine-related drugs (BZ/Z) in older people is common and not without risks. The objective of this study was to evaluate whether the implementation of a clinical rule promotes the discontinuation of chronically used BZ/Z for insomnia. METHODS: A clinical rule, generating an alert in case of chronic BZ/Z use, was created and applied to the nursing home (NH) setting. The clinical rule was a one-off intervention, and alerts did not occur over time. Reports of the generated alerts were digitally sent to NH physicians with the advice to phase out and eventually stop the BZ/Z. In cases where the advice was adopted, a follow-up period of 4 months on the use of BZ/Z was taken into account in order to determine whether the clinical rule alert led to a successful discontinuation of BZ/Z. RESULTS: In all, 808 NH patients were screened. In 161 (19.1%) of the patients, BZ/Z use resulted in a clinical rule alert. From these, the advice to phase out and stop the BZ/Z was adopted for 27 patients (16.8%). Reasons for not following the advice consisted of an unsuccessful attempt in the past (38 patients), patients family and/or patient resistance (37 patients), the non-continuous use of BZ/Z (32 patients) and indication still present (27 patients). Of the 12 NH physicians, seven adopted the advice. CONCLUSIONS: The success rate of a clinical rule for discontinuation of chronically used BZ/Z for insomnia was low, as reported in the present study. Actions should be taken to help caregivers, patients and family members understand the importance of limiting BZ/Z use to achieve higher discontinuation rates.

Factors that influence treatment decision-making in elderly DLBCL patients: a case vignette study.

Elderly patients with diffuse large B-cell lymphoma (DLBCL) are frequently not treated with standard immunochemotherapy, and this influences survival negatively. The purpose of this study was to gain more insight into treatment decision-making by hematologists. Case vignettes concerning patients with DLBCL were presented to hematologists in the Netherlands. Patient characteristics (age, comorbidity) differed per case. Respondents were asked in each case if they would treat the patient with curative intent by means of full-dose chemotherapy or chemotherapy with dose reduction or if they would not treat the patient with curative intent. The vast majority of respondents would treat an elderly patient diagnosed with DLBCL without a relevant medical history with full-dose chemotherapy irrespective of age. In the presence of comorbidity, lack of social support, cognitive disorders, and untreated depression dose reductions in advance are frequently applied or patients are not treated with curative intent. This is most pronounced for patients aged older than 80 years. Respondents working in a university hospital more frequently refrain form full-dose chemotherapy with curative intent compared to respondents working in tertiary medical teaching hospitals or general hospitals. Patients without a relevant medical history are generally treated with curative intent irrespective of age. Cognitive disorders, comorbidity, and depression reduce the change of being treated with curative intent. This is most prominent in the eldest patient category.

Risk modelling of outcome after general and trauma surgery (the IRIS score).

BACKGROUND: A practical, easy to use model was developed to stratify risk groups in surgical patients: the Identification of Risk In Surgical patients (IRIS) score. METHODS: Over 15 years an extensive database was constructed in a general surgery unit, containing all patients who underwent general or trauma surgery. A logistic regression model was developed to predict mortality. This model was simplified to the IRIS score to enhance practicality. Receiver operating characteristic (ROC) curve analysis was performed. RESULTS: The database contained a consecutive series of 33 224 patients undergoing surgery. Logistic regression analysis gave the following formula for the probability of mortality: P (mortality) = A/(1 + A), where A = exp (-4.58 + (0.26 x acute admission) + (0.63 x acute operation) + (0.044 x age) + (0.34 x severity of surgery)). The area under the ROC curve (AUC) was 0.92. The IRIS score also included age (divided into quartiles, 0-3 points), acute admission, acute operation and grade of surgery. The AUC predicting postoperative mortality was 0.90. CONCLUSION: The IRIS score accurately predicted mortality after general or trauma surgery.

Clinical practice: drug desensitization in children.

Immediate type allergic reactions to medication are potentially life threatening and can hamper drug therapy of several medical conditions. Exact incidence and prevalence data for these reactions in children are lacking. If no alternative drug treatment is available, a desensitization procedure may secure the continuation of necessary therapy. Desensitization is only appropriate in case of a strong suspicion of an IgE-mediated allergic reaction. It should be performed by trained clinicians (allergy specialists) in a hospital setting where treatment of a potential anaphylactic reaction can be done without any delay. In this article, literature describing desensitization procedures for several antibiotics, antineoplastic agents, and vaccines in children is reviewed. In general, desensitization schemes for children differ only in final dose from schemes for adults. Contradictory data were found regarding the protective effects of premedication with antihistamines and glucocorticoids.

Patients' representations of their end-stage renal disease: relation with mortality.

BACKGROUND: Self-regulation theory explains how patients' illness perceptions influence self-management behaviour (e.g. via adherence to treatment). Following these assumptions, we explored whether illness perceptions of ESRD-patients are related to mortality rates. METHODS: Illness perceptions of 182 patients participating in the NECOSAD-2 study in the period between December 2004 and June 2005 were assessed. Cox proportional hazard models were used to estimate whether subsequent all-cause mortality could be attributed to illness perception dimensions. RESULTS: One-third of the participants had died at the end of the follow-up. Mortality rates were higher among patients who believed that their treatment was less effective in controlling their disease (perceived treatment control; RR = 0.71, P = 0.028). This effect remained stable after adjusting for sociodemographic and clinical variables (RR = 0.65, P = 0.015). CONCLUSIONS: If we consider risk factors for mortality, we tend to rely on clinical parameters rather than on patients' representations of their illness. Nevertheless, results from the current exploration may suggest that addressing patients' personal beliefs regarding the effectiveness of treatment can provide a powerful tool for predicting and perhaps even enhancing survival.

[Changes in crisis intervention and emergency psychiatry, Amsterdam emergency consultations in 1983 and 2005]. / Veranderingen in crisisinterventie en acute psychiatrie; Amsterdamse consulten in 1983 en 2005.

BACKGROUND: Since 1992 The Netherlands has seen a striking increase in the number of compulsory admissions. There is a danger that coercion will become the dominant form of treatment in the Amsterdam clinics. AIM: To build up a picture of the changes in emergency psychiatry which have contributed to the increase in the number of acute compulsory admissions. METHOD: A cohort (n = 460) of consultations conducted by the city crisis service in 1983 was compared with a similar cohort (n = 436) of consultations conducted in 2004-2005 based on the following variables: crisis-service procedures, patient characteristics, diagnosis and consultation outcomes. RESULTS: In 2003-2004 more services were involved with psychiatric patients in acute situations in the public domain than were involved in 1983. The number of patients referred by the police almost doubled, rising from 29.3 to 62.7%. In 1983 all consultations took place where the patients were located; in 2004-2005 60% took place at the premises of the crisis service. The number of psychotic patients in the cohort rose from 52 to 63.3%. There was a rise in the number of compulsory admissions (from 16.7 to 20%) and a sharp decline in voluntary admissions (from 25.7 to 7.6%). The total number of admissions following a consultation decreased from 42 to 28%. CONCLUSIONS: The front-line outreach service of 1983 has been transformed into a specialist psychiatric emergency department with only a modest outreach component. Voluntary admissions via the consultation service have almost ceased. Further research is needed into the characteristics of the consultations and into the variables that play a role in the use of compulsion in emergency psychiatry.

[Smoking and doctors: from 'therapeutic panacea' to 'tobacco use discouragement in the individual']. / Roken en artsen: van 'geneeskrachtig wondermiddel' tot 'individuele tabaksontmoediging'.

In The Netherlands smoking will be prohibited in bars, restaurants, pubs and enclosed public spaces on 1 July 2008, in accordance with European legislation. Smoking is already not allowed in most Dutch hospitals. Europeans have a long history of tobacco smoking, going back to the introduction of this habit by Columbus. For centuries tobacco was used as a medicine, and later as a recreational drug, especially after the introduction of the cigarette. There was no scientific understanding of the harmful effects of smoking until the 19th century, when nicotine was isolated and recognised as a poison. Despite the fact that health care professionals represent a valuable resource for tobacco control, doctors have generally shown a poor appreciation of their critical role in smoking control. A decreasing smoking prevalence in the general population however, will emphasize the function of physicians as role model.

Energy consumption and water-soluble protein release by cell wall disruption of Nannochloropsis gaditana.

Several cell disruption methods were tested on Nannochloropsis gaditana, to evaluate their efficiency in terms of cell disintegration, energy input and release of soluble proteins. High-pressure homogenization (HPH) and bead milling were the most efficient with >95% cell disintegration, ±50% (w/w) release of total proteins and low energy input (<0.5kWh.kg-1biomass). Enzymatic treatment required low energy input (<0.34kWh.kg-1biomass), but it only released ±35% protein (w/w). Pulsed Electric Field (PEF) was neither energy-efficient (10.44kWh.kg-1biomass) nor successful for protein release (only 10% proteins w/w) and cell disintegration. The release of proteins after applying HPH and bead milling always required less intensive operating conditions for cell disruption. The energy cost per unit of released protein ranged from 0.15-0.25 €.kgProtein-1 in case of HPH, and up to 2-20 €.kgProtein-1 in case of PEF.

Biorefinery of microalgal soluble proteins by sequential processing and membrane filtration.

A mild biorefinery process was investigated on the microalga Nannochloropsis gaditana, to obtain an enriched fraction of water soluble proteins free from chlorophyll. After harvesting, a 100g.L-1 solution of cells was first subjected to cell disruption by either high-pressure homogenization (HPH) or enzymatic treatment (ENZ). HPH resulted in a larger release of proteins (49%) in the aqueous phase compared to the Alcalase incubation (35%). In both cases, an ultrafiltration/diafiltration (UF/DF) was then performed on the supernatant obtained from cell disruption by testing different membrane cut-off (1000kDa, 500kDa and 300kDa). After optimising the process conditions, the combination of ENZ→UF/DF ended in a larger overall yield of water soluble proteins (24.8%) in the permeate compared to the combination of HPH→UF/DF (17.4%). A gel polarization model was implemented to assess the maximum achievable concentration factor during ultrafiltration and the mass transfer coefficient related to the theoretical permeation flux rate.

Characterisation and foaming properties of hydrolysates derived from rapeseed isolate.

Two hydrolysis methods used to obtain rapeseed isolate derivates were compared: chemical hydrolysis performed under alkaline conditions and pepsic proteolysis performed under acidic conditions. The mean molecular weights obtained for the hydrolysates varied from 26 to 2.5 kDa, depending on the level of hydrolysis. Further characterisation showed that, at the same level of hydrolysis, the chemical hydrolysates differed by their charges and hydrophobicity from those derived from enzymatic digestion. Analysis of the foaming properties showed, for both cases, that a limited degree of hydrolysis, around 3%, was sufficient to optimise the foaming properties of the isolate despite the different physicochemical properties of the peptides generated. The study of foaming properties at basic, neutral and acidic pHs showed that the hydrolysate solutions yielded dense foams which drained slowly and which maintained a very stable volume under the three pH conditions tested.

Validity, Reliability and Feasibility of Tools to Identify Frail Older Patients in Inpatient Hospital Care: A Systematic Review.

BACKGROUND: The objective of this study is to identify and review screening tools for frailty in older adults admitted to inpatient hospital care with respect to their validity, reliability and feasibility. METHODS: Studies were identified through systematically searching PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and PsycINFO and screening reference lists till June 2014. Papers dealing with screening tools aimed at identifying frail older patients in in-hospital care, and including information about validity, reliability or feasibility, were included in the review. The quality of the included studies was critically appraised via the Quality Assessment of Diagnostic Accuracy Studies (QUADAS). RESULTS: From the originally identified 2001 studies 32 studies met the inclusion criteria, in which 16 screening tools were presented. The screening tools showed different characteristics with respect to the number of items, the method of administration and the domains included. The most frequently studied tools with respect to predictive validity were the Identification Seniors At Risk (ISAR) and Triage Risk Stratification Tool (TRST). Studies retrieved poorer information about reliability and feasibility. Overall sensitivity was fairly good. The ISAR, ISAR-HP (Identification Seniors At Risk Hospitalized Patients) and Multidimensional Prognostic Index (MPI) generally had the best sensitivity. CONCLUSIONS: Many screening tools are available for daily practice. These tools to identify frail older patients in inpatient hospital care could be useful. For no tool, however, is clear evidence available yet regarding validity, reliability and feasibility. The overall sensitivity of the included screening tools was fairly good, whereas information on reliability and feasibility was lacking for most tools. In future research more attention should be given to the latter items.

Usually Available Clinical and Laboratory Data Are Insufficient for a Valid Medication Review: A Crossover Study.

OBJECTIVES: To establish the quality of medication reviews performed by nursing home physicians, general practitioners and pharmacists. DESIGN AND SETTING: 15 Pharmacists, 13 general practitioners and 18 nursing home physicians performed a medication review for three cases (A, B and C), at three evaluation moments. First, they received the medication list. Secondly, they also received laboratory results and reason for admission and finally, we added medical history. Remarks were divided into 6 categories, i.e. indication without medication, medication without indication, contraindications/ interactions, dosage problems, double medication and wrong medication. Remarks were compared to the remarks made by our expert panel and scored according to our grading model as appropriate (0 to +3) or missed or potentially harmful (-1). For each medication error category, the percentage of participants who made this error was computed. RESULTS: After the first evaluation moment, the overall estimated mean percentage score was -1.7% for case A, 3.9% for case B, and 8.7% for case C. After the second review, this score was 15.0% for case A, 19.8% for case B, and 22.2% for case C. This further increased to 30.0% for case A, 36.7% for case B and 44% for case C at the final evaluation. The absence of medication where there was an indication (indication without medication) was frequently missed and did not improve after adding the extra information regarding laboratory results, reason for admission and finally medical history. CONCLUSION: Increasing clinical information helps physicians and pharmacists to improve their medication reviews, however, additional information was still related with a high margin of error. Detection of certain errors becomes easier with additional information, whereas other errors remain undetected. To achieve a high standard of medication review, we have to change the way medication reviews should be performed.

Isolation and characterisation of the linked genes, FPS1 and QCR8, coding for farnesyl-diphosphate synthase and the 11 kDa subunit VIII of the mitochondrial bc1-complex in the yeast Kluyveromyces lactis.

The KlQCR8 gene of the yeast Kluyveromyces lactis encoding subunit VIII of the mitochondrial bc1 complex is 70.2% identical to its counterpart in Saccharomyces cerevisiae (ScQCR8). As in S. cerevisiae, chromosomal linkage between the K. lactis QCR8 and FPS1 genes is conserved, the two genes being separated by only 292 bp. Disruption of the KlQCR8 gene results in a respiratory-deficient phenotype. Compared with S. cerevisiae, expression of the KlQCR8 gene in glucose-grown cells is relatively high, yet is significantly induced when the cells are grown on non-fermentable carbon sources. The QCR8 promoters regions of the two yeasts lack overall DNA sequence similarity, but share DNA-binding sites for the transcription factors ABF1, CPF1 and HAP2/3/4. Deletion from the KlQCR8 promoter of a 93 bp region containing these sites significantly lowers mRNA levels during growth on either glucose or ethanol/glycerol, with a consequent reduction of growth rate on ethanol/glycerol.

Isolation and characterisation of the linked genes APA2 and QCR7, coding for Ap4A phosphorylase II and the 14 kDa subunit VII of the mitochondrial bc1-complex in the yeast Kluyveromyces lactis.

We report the isolation and characterization of the KlQCR7 gene encoding subunit VII of the mitochondrial bc1 complex of the yeast Kluyveromyces lactis. The coding region is 69.3% identical to its counterpart in Saccharomyces cerevisiae (ScQCR7). Like the KlQCR8 gene (Mulder et al., accompanying paper) expression of the KlQCR7 gene during growth on glucose is high and can be further induced when cells are grown on non-fermentable carbon sources. The chromosomal linkage of the APA2 and QCR7 genes is conserved between S. cerevisiae and K. lactis. The intergenic regions containing the QCR7 promoters of the two yeasts, differ significantly in length and lack overall DNA sequence similarity, but they do share a binding site for the transcription factor complex HAP2/3/4. The KlQCR7 promoter contains, in addition, a CPF1 consensus binding site which is absent from ScQCR7. Deletion of a 35 bp region containing these two sites severely lowers the mRNA expression during growth on both glucose and ethanol/glycerol, but growth rate on both carbon sources is only mildly affected. Interestingly, in respect to the KlQCR7 gene, KlCPF1 seems to act as an important transcriptional activator, thus contrasting the proposed repressor function of ScCPF1 for the ScQCR8 gene of S. cerevisiae.

In vitro expression of bovine opsin using recombinant baculovirus: the role of glutamic acid (134) in opsin biosynthesis and glycosylation.

Expression levels of functional bovine opsin in the insect cell line IPLB-Sf9 using recombinant baculovirus were shown not to depend on the use of novel transfer vectors (pAcRP23, pAcDZ1) that were reported to improve biosynthesis levels of other proteins in this system. A production of 5 micrograms opsin per 10(6) cells (approx. 1.5% of total cell protein) was achieved by batch fermentation of infected cells in spinner cultures. Infection of the cells in the presence of the glycosyltransferase inhibitor tunicamycin led to the synthesis of the complete protein, which, however, now migrated with a substantially lower Mr. This demonstrates that opsin in insect cells also undergoes N-linked glycosylation and allowed partial purification (10-fold) of the resulting rhodopsin by affinity chromatography over Concanavalin A-Sepharose. Through site-directed mutagenesis (rhod)opsin mutants have been obtained allowing dissection of functional domains of opsin. Amino acid substitutions that involved Glu-134 and/or Arg-135 affected the normal biosynthetic process leading in part to nonglycosylated, to a small extent even incomplete, protein. A number of mutations, that involve other charged residues within the second and third transmembrane domain of the protein, had no effect on the biosynthetic processing of the protein. We therefore suggest that the charge-pair Glu-134-Arg-135 is part of an important internal signal sequence and that alterations in this region may result in incorrect membrane translocation and/or folding of the protein.

Low intercellular adhesion molecule 1 and high 5T4 expression on tumor cells correlate with reduced disease-free survival in colorectal carcinoma patients.

The purpose of this study was to investigate the prognostic value of the expression of intercellular adhesion molecule 1 (ICAM-1), leukocyte function antigen 3 (LFA-3), human leukocyte differentiation antigen (HLA)-ABC, HLA-DR, and 5T4 with regard to disease-free survival in Dukes' B and C colorectal carcinoma patients. Forty-one patients (28 Dukes' B and 13 Dukes' C) were entered into this study. Immunocytochemistry was performed on cytospin preparations of enzymatically digested colorectal carcinoma cell suspensions. The frequency of metastases and the duration of disease-free survival were compared between the 25% lowest expressers and the 75% remaining patients for ICAM-1, LFA-3, HLA-ABC, and HLA-DR, and between the 25% highest expressers and the 75% remaining patients for 5T4. Low numbers of ICAM-1-expressing tumor cells were associated with a shorter disease-free survival (P < 0. 001), independent of Dukes' stage. High numbers of 5T4-expressing tumor cells were associated with shorter disease-free survival in Dukes' B patients (P = 0.04). Cox proportional hazard analysis indicated that low numbers of ICAM-1(+) and high numbers of 5T4(+) cells were independent prognostic factors with relative risks of 13. 0 (P = 0.0002) and 4.7 (P = 0.02), respectively. The combination of 5T4 and ICAM-1 marker information identified subgroups of patients with a good (high ICAM-1) or poor (low ICAM-1/high 5T4) prognosis. Neither a lack of HLA-ABC and LFA-3 expression nor the presence of HLA-DR on the tumor cells gave additional prognostic information. These findings demonstrate that low ICAM-1 and high 5T4 expression on tumor cells are prognostic markers, additional to Dukes' stage, for reduced disease-free survival in Dukes' B and C colorectal carcinoma patients.

Antiestrogens specifically up-regulate bone morphogenetic protein-4 promoter activity in human osteoblastic cells.

Bone morphogenetic protein-4 (BMP-4) plays an important role in the onset of endochondral bone formation in humans, and a reduction in BMP-4 expression has been associated with a variety of bone diseases. Here we describe, by transient transfection assays in bone cells, that the human BMP-4 promoter recently characterized in our laboratory can be stimulated specifically by antiestrogens but not by estrogens or other steroid hormones. This activity is dependent on the presence of the estrogen receptor (ER)-alpha, although the promoter lacks a consensus estrogen-responsive element. No activity was observed in the presence of ERbeta, but synergy was observed when both ER subtypes were cotransfected. The observed stimulation of BMP-4 promoter activity by antiestrogens appeared bone cell specific and was reversed upon addition of estrogens. Since antiestrogens are known to be effective in hormone replacement therapies for postmenopausal women, this observation may help to develop new strategies for treatment and prevention of osteoporosis.