Internet-based emotion regulation training aimed at reducing violent revictimization and depressive symptoms in victimized depressed patients: Results of a randomized controlled trial.

BACKGROUND: Depressed patients who have become victim of violence are prone to revictimization. However, no evidence-based interventions aimed at reducing revictimization in this group exist. METHODS: This multicenter randomized controlled trial evaluated the effectiveness of an internet-based emotion regulation training (iERT) added to TAU in reducing revictimization, emotion dysregulation, and depressive symptoms in recently victimized, depressed patients compared to TAU alone. Adult outpatients (N = 153) with a depressive disorder who had experienced threat, physical assault, or sexual assault within the previous three years were randomly allocated to TAU+iERT (n = 74) or TAU (n = 79). TAU involved psychotherapy (mainly cognitive behavioral therapy [77.8 %]). iERT comprised six guided online sessions focused on the acquisition of adaptive emotion regulation skills. The primary outcome measure was the number of revictimization incidents at 12 months after baseline, measured with the Safety Monitor. Analyses were performed according to the intention-to-treat principle. RESULTS: Both groups showed a large decrease in victimization incidents. Mixed-model negative binomial regression analyses showed that TAU+iERT was not effective in reducing revictimization compared to TAU (IRR = 0.97; 95%CI = 0.64,1.46; p = .886). Linear mixed-model analyses demonstrated that TAU+iERT yielded a larger reduction of emotion dysregulation (B = -7.217; p = .046; Cohens d = 0.33), but not depressive symptoms (B = -1.041; p = .607) than TAU. LIMITATIONS: The study was underpowered to detect small treatment effects. Additionally, uptake of iERT was quite low. CONCLUSIONS: Although TAU+iERT resulted in a larger decrease of emotion dysregulation than TAU alone, it was not effective in reducing revictimization and depressive symptoms. Patients' revictimization risk substantially decreased during psychotherapy.

The association between child maltreatment and problematic alcohol use in adulthood in a large multi-ethnic cohort: the HELIUS study.

AIMS: There is evidence that child maltreatment is associated with problematic alcohol use later in life. However, previous epidemiological studies that have examined the link between child maltreatment and adult problematic alcohol use have not considered ethnic differences. Therefore, the purpose of the current study was to investigate the relationship between child maltreatment and adult problematic alcohol use among six ethnic groups in the Netherlands, in a large, urban sample. METHODS: This study used baseline data from the Healthy Life in an Urban Setting (HELIUS) study: a large-scale, multi-ethnic prospective cohort study conducted in Amsterdam, the Netherlands. Child maltreatment, current problematic alcohol use and several potential confounders (e.g. parental alcohol use) were assessed in participants (N = 23 356) of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish and Moroccan origin. With logistic regression analyses, we examined effect modification by ethnicity on the association between child maltreatment and problematic alcohol use. Furthermore, we explored effect modification by ethnicity for specific types of child maltreatment, namely: physical, sexual and psychological abuse and emotional neglect. RESULTS: Effect modification by ethnicity was present. Stronger associations between child maltreatment and problematic alcohol use were found in all ethnic minority groups compared to the Dutch reference group. Particularly strong associations between all four types of child maltreatment and alcohol use problems were found for the Moroccan origin group. CONCLUSIONS: This study adds to a growing body of evidence that child maltreatment is associated with problematic alcohol use in adulthood. In addition, our findings indicate that ethnicity impacts this relationship. Although problematic alcohol use was more prevalent in the Dutch origin group, associations with child maltreatment were stronger in ethnic minority groups. Future studies on child maltreatment and alcohol use problems should also examine ethnic disparities and should further unravel how these disparities can be explained.

Violent victimization and revictimization in patients with depressive disorders: context characteristics, disclosure rates, and gender differences.

BACKGROUND: Depressed patients are prone to violent victimization, and patients who were victimized once are at increased risk to fall victim to violence again. However, knowledge on the context of victimization in depressed patients is lacking, and research identifying targets for prevention is urgently needed. METHODS: This cross-sectional study explored context characteristics, disclosure rates and gender differences regarding violent victimization in 153 recently victimized depressed patients. Additionally, 12-month prevalence rates of repeat threat, physical assault, and sexual assault were examined, and gender differences were investigated using t-tests, Chi-square tests, and Fisher's exact tests. Furthermore, logistic regression analyses were used to identify factors associated with repeat victimization. RESULTS: Overall, depressed men were most often victimized by a stranger in public, and women by their partner or ex-partner at home. Regarding sexual assault, no gender differences could be examined. Patients were sexually assaulted most often by an acquaintance (50.0%) or stranger (27.8%). In all patients, the most recent incidents of threat (67.6%) and physical assault (80.0%) were often preceded by a conflict, and only a minority had been intoxicated prior to the assault. Notably, less than half of patients had disclosed their recent experience of threat (40.6%) and physical assault (47.1%) to their mental health caregiver. For sexual assault, this was only 20%. Less than one third of patients had reported their recent experience of threat (27.9%), physical assault (30.0%) and sexual assault (11.1%) to the police. 48.4% of patients had been victimized repeatedly in the past year, with no gender differences found. Only depressive symptoms and unemployment were univariately associated with repeat victimization, but not in the multiple model. CONCLUSIONS: The high prevalence of repeat victimization in depressed patients and their low disclosure rates stress the need to implement routine enquiry of victimization in mental health care, and to develop preventive interventions accounting for specific needs of men and women.

Coded diagnoses from general practice electronic health records are a feasible and valid alternative to self-report to define diabetes cases in research.

AIMS: To examine the feasibility and validity of obtaining International Classification of Primary Care (ICPC)-coded diagnoses of diabetes mellitus (DM) from general practice electronic health records for case definition in epidemiological studies, as alternatives to self-reported DM. METHODS: The Netherlands Epidemiology of Obesity study is a population-based cohort study of 6671 persons aged 45-65 years at baseline, included between 2008-2012. Data from electronic health records were collected between 2012-2014. We defined a reference standard using diagnoses, prescriptions and consultation notes and investigated its agreement with ICPC-coded diagnoses of DM and self-reported DM. RESULTS: After a median follow-up of 1.8 years, data from 6442 (97%) participants were collected. With the reference standard, 506 participants (79/1000 person-years) were classified with prevalent DM at baseline and 131 participants (11/1000 person-years) were classified with incident DM during follow-up. The agreement of prevalent DM between self-report and the reference standard was 98% (kappa 0.86), the agreement between ICPC-coded diagnoses and the reference standard was 99% (kappa 0.95). The agreement of incident DM between ICPC-coded diagnoses and the reference standard was >99% (kappa 0.92). CONCLUSIONS: ICPC-coded diagnoses of DM from general practice electronic health records are a feasible and valid alternative to self-reported diagnoses of DM.

[Victimization among dual diagnosis patients and effectiveness of the sos training]. / Victimisatie van patiënten met een dubbele diagnose en effectiviteit van de groepsinterventie sos training.

BACKGROUND: Patients with a co-occurring substance use disorder and other mental disorder (dual diagnosis) are at increased risk of victimization: to become victims of for instance physical abuse, sexual abuse, and property crimes.
AIM: To examine the effectiveness of the sos training: a new group-based intervention to improve resilience of dual diagnosis patients and thereby reduce their risk of victimization.
METHOD: A randomized controlled trial was conducted in dual diagnosis patients, with a 14-month follow-up period. Patients were randomized to receive either care as usual (n = 125), or care as usual plus sos training (n =125). The primary outcome measure was defined as treatment response for victimization (yes/no), with 'yes' defined as at least a 50% reduction in the number of past-year victimization incidents at 14-month follow-up compared to baseline.
RESULTS: Significantly more participants in the experimental group achieved positive treatment response for victimization (68%) compared to the control group (54%).
CONCLUSION: Adding sos training to care as usual in dual diagnosis patients is more effective in reducing victimization compared to care as usual alone. The sos training can be implemented in addiction-psychiatry services to prevent future victimization in these patients.

Depressive subtypes in an elderly cohort identified using latent class analysis.

BACKGROUND: Clinical findings indicate heterogeneity of depressive disorders, stressing the importance of subtyping depression for research and clinical care. Subtypes of the common late life depression are however seldom studied. Data-driven methods may help provide a more empirically-based classification of late-life depression. METHODS: Data were used from the Netherlands Study of Depression in Older People (NESDO) derived from 359 persons, aged 60 years or older, with a current diagnosis of major depressive disorder. Latent class analysis (LCA) was used to identify subtypes of depression, using ten CIDI-based depression items. Classes were then characterized using various sociodemographic and clinical characteristics. RESULTS: The most prevalent class, as identified by LCA, was a moderate-severe class (prevalence 46.5%), followed by a severe melancholic class (prevalence 38.4%), and a severe atypical class (prevalence 15.0%). The strongest distinguishing features between the three classes were appetite and weight and, to a lesser extent, psychomotor symptoms and loss of interest. Compared with the melancholic class, the severe atypical class had the highest prevalence of females, the lowest mean age, the highest BMI, and highest prevalence of both cardiovascular disease, and metabolic syndrome. LIMITATIONS: The strongest distinguishing symptoms, appetite and weight, could be correlated. Further, only longitudinal studies could demonstrate whether the identified classes are stable on the long term. DISCUSSION: In older persons with depressive disorders, three distinct subtypes were identified, similar to subtypes found in younger adults. The strongest distinguishing features were appetite and weight; moreover, classes differed strongly on prevalence of metabolic syndrome and cardiovascular disease. These findings suggest differences in the involvement of metabolic pathways across classes, which should be considered when investigating the pathogenesis and (eventually) treatment of depression in older persons.

Extensive calcification of the ligamentum flavum causing cervical myelopathy in a Caucasian woman.

Calcification of the ligamentum flavum (CLF) can cause myelopathy due to spinal cord compression. Only several cases in Caucasian patients have been described. Neurological deterioration can only be stopped by surgical decompression. We report a 63-year-old Caucasian woman presenting with progressive pins-and-needles sensations in both hands, worsened by painful paresthesia in both lower extremities. MRI showed a dorsal compressive mass extending from C2 to Th3 vertebrae with myelopathy at the level of C6. A laminectomy was performed, which improved clinical symptoms. Histological examination showed CLF. Early recognition of CLF and early spinal cord decompression are needed to improve neurological outcome.

The effect of pain on presence and severity of depressive disorders in older persons: The role of perceived control as mediator.

BACKGROUND: The relation between pain and depression is reported repeatedly. It is suggested that pain by itself is not sufficient for the development of depression. We aim to study the role of perceived control as mediating factor in the relation between pain and depressive disorders at old age. METHODS: Baseline data of the Netherlands Study of Depression in Older Persons (NESDO) were used, including 345 persons with DSM-IV depressive disorders (CIDI) and 125 control persons without depressive disorders, aged 60 years and over. Measures included severity of depression (Inventory of Depressive Symptomatology), presence and intensity of pain and pain-related disability (Chronic Graded Pain scale), and a general measure of perceived control over life (Pearlin Mastery Scale). In mediation analyses direct and indirect effects were estimated. RESULTS: Older persons with depressive disorders reported pain more frequently with higher intensity than controls. After controlling for confounding, the direct effect of pain intensity and the indirect effect through perceived control on depression were OR=1.10 (CI 95% .98;1.25) and OR=1.24 (1.15;1.35). For pain-related disability these were OR=1.14 (1.02;1.29) and OR=1.21 (1.13;1.29). In depressed persons there was a strong direct effect of pain intensity and disability and a smaller indirect effect through perceived control on severity of depressive symptoms. LIMITATIONS: This cross-sectional study cannot give evidence on causal direction. CONCLUSIONS: Perceived control plays an important role as mediator in the association between pain and presence of depression. In depressed persons however, the direct role of pain seems more important in the association with depression severity.

CYP2D6 Metabolism in Frail Elderly Compared to Non-Frail Elderly: A Pilot Feasibility Study.

BACKGROUND: Frailty is a clinical phenotype that is associated with adverse health outcomes. Since frail patients may be more prone for adverse drug events and about 15-20 % of commonly prescribed drugs are metabolized by CYP2D6, we hypothesized that CYP2D6 metabolism is decreased in frail patients compared with healthy subjects. METHODS: The (13)C-dextromethorphan breath test (DM-BT) was used to determine CYP2D6 phenotype using (13)C-dextromethorphan ((13)C-DM) as a probe. Eleven frail and 22 non-frail (according to the Fried criteria) subjects aged 70-85 years were phenotyped for CYP2D6. RESULTS: Despite inequalities in CYP2D6 genotype between frail and non-frail subjects, the CYP2D6 gene activity score was equally distributed between the two groups (1.33 ± 0.50 vs. 1.28 ± 0.752). In male patients, no difference in total and free serum testosterone levels was observed between frail and non-frail men. Serum dehydroepiandrostenedione sulfate (DHEAS) levels were lower in frail subjects (1.56 µmol/L) compared with non-frail subjects (2.36 µmol/L), but the difference was not significant (p = 0.15). Body mass index was significantly correlated to CYP2D6 phenotype, whereas frailty score and individual parameters of frailty, Karnofsky score, and activities of daily living score were not significantly correlated to CYP2D6 phenotype. Although there was no difference in CYP2D6 phenotype observed between frail mean ± standard deviation (mean ± SD) area under the curve for delta over baseline values (0-2 h) (AUCDOB2h) 319 ± 169 ‰ min] and non-frail subjects (mean ± SD AUCDOB2h 298 ± 159 ‰ min), the present sample size is considered too small to draw any firm conclusions regarding a potential phenoconversion of CYP2D6 in frail elderly as compared with healthy subjects. CONCLUSION: Frail and non-frail subjects did not differ in CYP2D6 phenotype, taking into account that the precalculated sample size was not achieved. Further studies with more patients are needed in order to adequately understand a possible correlation.

Depression in later life: a more somatic presentation?

BACKGROUND: Depression later in life may have a more somatic presentation compared with depression earlier in life due to chronic somatic disease and increasing age. This study examines the influence of the presence of chronic somatic diseases and increasing age on symptom dimensions of late-life depression. METHODS: Baseline data of 429 depressed and non-depressed older persons (aged 60-93 years) in the Netherlands Study of Depression in Old Age were used, including symptom dimension scores as assessed with the mood, somatic and motivation subscales of the Inventory of Depressive Symptomatology-Self Report (IDS-SR). Linear regression was performed to investigate the effect of chronic somatic diseases and age on the IDS-SR subscale scores. RESULTS: In depressed older persons a higher somatic disease burden was associated with higher scores on the mood subscale (B = 2.02, p = 0.001), whereas higher age was associated with lower scores on the mood (B = -2.30, p < 0.001) and motivation (B = -1.01, p = 0.006) subscales. In depressed compared with non-depressed persons, a higher somatic disease burden showed no different association with higher scores on the somatic subscale (F(1,12) = 9.2; p = 0.003; partial η(2)=0.022). LIMITATIONS: Because the IDS-SR subscales are specific for old age, it was not feasible to include persons aged < 60 years to investigate differences between earlier and later life. CONCLUSIONS: It seems that neither higher somatic disease burden nor higher age contributes to more severe somatic symptoms in late-life depression. In older old persons aged ≥ 70 years, late-life depression may not be adequately recognized because they may show less mood and motivational symptoms compared with younger old persons.

Do practice characteristics explain differences in morbidity estimates between electronic health record based general practice registration networks?

BACKGROUND: General practice based registration networks (GPRNs) provide information on population health derived from electronic health records (EHR). Morbidity estimates from different GPRNs reveal considerable, unexplained differences. Previous research showed that population characteristics could not explain this variation. In this study we investigate the influence of practice characteristics on the variation in incidence and prevalence figures between general practices and between GPRNs. METHODS: We analyzed the influence of eight practice characteristics, such as type of practice, percentage female general practitioners, and employment of a practice nurse, on the variation in morbidity estimates of twelve diseases between six Dutch GPRNs. We used multilevel logistic regression analysis and expressed the variation between practices and GPRNs in median odds ratios (MOR). Furthermore, we analyzed the influence of type of EHR software package and province within one large national GPRN. RESULTS: Hardly any practice characteristic showed an effect on morbidity estimates. Adjusting for the practice characteristics did also not alter the variation between practices or between GPRNs, as MORs remained stable. The EHR software package 'Medicom' and the province 'Groningen' showed significant effects on the prevalence figures of several diseases, but this hardly diminished the variation between practices. CONCLUSION: Practice characteristics do not explain the differences in morbidity estimates between GPRNs.

Depression, disability and somatic diseases among elderly.

OBJECTIVE: Depression among older adults is associated with both disability and somatic disease. We aimed to further understand this complicated relationship and to study the possible modifying effect of increasing age. DESIGN: Cross sectional survey. SETTING: Outpatient and inpatient clinics of regional facilities for mental health care and primary care. PARTICIPANTS: Elderly people, 60 years and older, 378 persons meeting DSM-IV criteria for a depressive disorder and 132 non-depressed comparisons. MEASUREMENTS: Depression diagnoses were assessed with the CIDI version 2.1. Disability was assessed with the WHO Disability Assessment Schedule (WHODAS). Social-demographic information and somatic diseases were assessed by self-report measurements. RESULTS: Disability, in general and on all its subscales, was strongly related to depression. Presence of somatic disease did not contribute independently to variance in depression. The relationship was stronger for people of 60-69 years old than for those older than 70 years. Important aspects of disability that contributed to depression were disability in participation, self-care and social activities. LIMITATIONS: Results are based on cross sectional data. No inferences about causal relationships can be drawn. CONCLUSION: Disability, especially disability regarding participation, self-care, or social activities is strongly related to late-life depression. Somatic diseases in itself are less of a risk for depression, except that somatic diseases are related to disability.

The subscale structure of the Inventory of Depressive Symptomatology Self Report (IDS-SR) in older persons.

BACKGROUND: Using symptom dimensions may be more effective than using categorical subtypes when investigating clinical outcome and underlying mechanisms of late-life depression. Therefore, this study aims to identify both the factor and subscale structure of late-life depression underlying the Inventory of Depressive Symptomatology Self Report (IDS-SR) in older persons. METHOD: IDS-SR data of 423 participants in the Netherlands Study of Depression in Older Persons (NESDO) were analyzed by exploratory (EFA) and confirmatory factor analysis (CFA). The best-fitting factor solution in a group of older persons with a major depressive disorder diagnosis in the last month (n = 229) was replicated in a control group of older persons with no or less severe depression (n = 194). Multiple group (MG-CFA) was performed to evaluate generalizability of the best-fitting factor solution across subgroups, and internal consistency coefficients were calculated for each factor. RESULTS: EFA and CFA show that a 3-factor model fits best to the data [comparative fit index (CFI) = 0.98; Tucker Lewis Index (TLI) = 0.99; and root mean square error of approximation (RMSEA) = 0.052], consisting of a 'mood', 'motivation' and 'somatic' factor with adequate internal consistencies (alpha coefficient 0.93, 0.83 and 0.70, respectively). MG-CFA shows a structurally similar factor model across subgroups. CONCLUSION: The IDS-SR can be used to measure three homogeneous symptom dimensions that are specific to older people. Application of these dimensions that may serve as subscales of the IDS-SR may benefit both clinical practice and scientific research.

The influence of population characteristics on variation in general practice based morbidity estimations.

BACKGROUND: General practice based registration networks (GPRNs) provide information on morbidity rates in the population. Morbidity rate estimates from different GPRNs, however, reveal considerable, unexplained differences. We studied the range and variation in morbidity estimates, as well as the extent to which the differences in morbidity rates between general practices and networks change if socio-demographic characteristics of the listed patient populations are taken into account. METHODS: The variation in incidence and prevalence rates of thirteen diseases among six Dutch GPRNs and the influence of age, gender, socio economic status (SES), urbanization level, and ethnicity are analyzed using multilevel logistic regression analysis. Results are expressed in median odds ratios (MOR). RESULTS: We observed large differences in morbidity rate estimates both on the level of general practices as on the level of networks. The differences in SES, urbanization level and ethnicity distribution among the networks' practice populations are substantial. The variation in morbidity rate estimates among networks did not decrease after adjusting for these socio-demographic characteristics. CONCLUSION: Socio-demographic characteristics of populations do not explain the differences in morbidity estimations among GPRNs.

Epidemiology of high-level parvovirus B19 viraemia among Dutch blood donors, 2003-2009.

BACKGROUND AND OBJECTIVES: Plasma derivatives and blood components with low levels of parvovirus B19 (B19) seem not infectious, but recently infected, highly viraemic donors may transmit B19. We studied the incidence of high-level B19 viraemia (B19 DNA>10(6) IU/ml) in 6.5 million Dutch blood donations. MATERIALS AND METHODS: Between 2003 and 2009, all Dutch blood and plasma donations were screened for the presence of B19 DNA, via pools of 480. Reactive pools were resolved and demographic parameters were obtained for all donors with B19 viraemia>10(6) IU/ml. In a subset, IgG and IgM antibodies to B19 were determined. RESULTS: Four hundred and eleven donations (1/15815) were identified with B19 DNA levels above 10(6) IU/ml, predominantly (83%) occurring in donors aged 18-47 years. Each year infection rates were elevated between December and July, with April accounting for 16% of infections. The years 2004 and 2009 were epidemic, with up to 1/4880 highly viraemic donations in May 2004. In a subset of 67 viraemic donations, 47/67 (70%) tested negative for IgG and IgM antibodies to B19; 16/67 (24%) showed isolated IgM and 4/67 (6%) contained IgG and IgM antibodies. The seasonal pattern of asymptomatic B19 infection in blood donors followed the notification rate of clinical cases. Geographically, B19 infection was randomly spread over the Netherlands. CONCLUSIONS: In epidemic seasons, blood donations with high levels of parvovirus, without concurrent antibodies, are common. They may infect immunocompromised and parvovirus-naïve recipients. The feasibility of preventive measures should be studied.

[Hyponatraemia as a clinical manifestation of hypopituitarism caused by neurosarcoidosis]. / Hyponatriëmie als klinische manifestatie van hypopituïtarisme door neurosarcoïdose.

Severe hyponatraemia was observed in a 35-year-old man with progressive malaise; this was caused by hypopituitarism and secondary hypocortisolism as a result ofneurosarcoidosis. Sarcoidosis is a multisystem granulomatous disorder of unknown aetiology which can develop in any of the body's organs or tissues. The central nervous system is affected in only 5-15% of patients with sarcoidosis. Neurosarcoidosis is a rare disorder with clinical heterogeneity. Extensive diagnostic procedures, including MRI of the cerebrum and histological investigation, and structural outpatient follow-up are mandatory in patients in whom neurosarcoidosis is suspected. Treatment consists mainly of high-dose corticosteroids, which usually have to be taken long-term. Clinical course and prognosis are variable, and depend on the accompanying symptoms.

[Somatoform disorders in general practice: prevalence, functional limitations and comorbidity with anxiety and depression]. / Somatoforme stoornissen in de huisartspraktijk: prevalentie, functionele beperkingen en comorbiditeit met angst en depressie.

OBJECTIVE: To quantify the prevalence of, and functional impairment associated with, somatoform disorders in general practice and their comorbidity with anxiety and depression. DESIGN: Prevalence study. METHOD: In the first phase of a two-stage prevalence study from April 2000 up to December 2001, a questionnaire was completed by 1046 consecutive attendees at general practices, aged 25-79 years (n = 1778). This was followed in the second phase by a standardised diagnostic interview ('Schedules for clinical assessment in neuropsychiatry'; SCAN 2.1) in a stratified sample of 473 patients. In the analyses, the prevalence figures were estimated by weighting back to the original attending population. RESULTS: The prevalence ofsomatoform disorders was 16% (95% CI: 12.8-19.4). Comorbidity of somatoform disorders and anxiety or depression disorders was 3.3 times more likely than would be expected by chance. Somatoform disorders as well as anxiety or depressive disorders were associated with substantial functional impairment. In patients with comorbid disorders, physical symptoms, depressive symptoms and functional limitations were proportionately increased. CONCLUSION: These findings underline the importance of a comprehensive diagnostic approach covering anxiety and depressive disorders as well as somatoform disorders in general practice.

No evidence of West Nile virus infection in Dutch blood donors.

BACKGROUND AND OBJECTIVES: West Nile virus (WNV) can be transmitted by transfusion through infected blood components. This study aimed to determine the prevalence of WNV infection among Dutch blood donors to assess whether WNV is a possible threat for the Dutch blood supply. MATERIALS AND METHODS: Plasma samples from 61 992 blood donations were pooled in 7,749 test pools of eight donations using a Tecan robot. These samples were collected between April and October 2004. The pools were tested for the presence of WNV RNA by using the Procleix WNV assay. RESULTS: No WNV RNA-positive pools were detected. Based on Poisson distribution statistics, extrapolation of our data to all the Dutch donations in 2004 revealed that between 0 and 55 cases of WNV infection could be expected. CONCLUSIONS: No evidence of the presence of WNV RNA in Dutch blood donor samples from 2004 was found. However, surveillance of this emerging infection is of importance to safeguard the blood supply in the future because the transmission cycle of WNV is complex and hard to predict.

Nutritional deficiency in Dutch primary care: data from general practice research and registration networks.

OBJECTIVE: To explore incidence and prevalence rates of nutritional deficiency in adults in general practice. METHODS: Six Dutch general practice research and registration networks supplied incidence and prevalence rates of nutritional deficiency by the International Classification of Primary Care (ICPC) or 'E-list' labels ('loss of appetite, feeding problem adult, iron, pernicious/folate deficiency anaemia, vitamin deficiencies and other nutritional disorders, weight loss'). In case of disease-related nutritional deficiency, we asked whether this was labelled separately ('co-registered') or included in the registration of the underlying disease. RESULTS: 'Iron deficiency anaemia' had highest incidence (0.3-8.5/1000 person years), and prevalence rates (2.8-8.9/1000 person years). Nutritional deficiency was mostly documented in the elderly. In two networks 'co-registration' was additional, two only documented the underlying disease and two did not specify 'co-registration'. No clear difference was found between networks considering the difference in 'co-registration'. CONCLUSION: Nutritional deficiency is little documented in general practice, and generally is not registered separately from the underlying disease.

Immunotherapy with concurrent subcutaneous GM-CSF, low-dose IL-2 and IFN-alpha in patients with progressive metastatic renal cell carcinoma.

The purpose of the study was to determine toxicity, efficacy and immunologic effects of concurrent subcutaneous injections of low-dose interleukin-2 (LD-IL-2), granulocyte-monocyte colony-stimulating factor (GM-CSF) and interferon-alpha 2b (IFNalpha) in progressive metastatic renal cell carcinoma. In a multicentre phase II study, 59 evaluable patients received two to six cycles of subcutaneous IL-2 (4 mIU m(-2)), GM-CSF (2.5 microg kg(-1)) and IFNalpha (5 mIU flat(-1)) for 12 days per 3 weeks with evaluation after every two cycles. Cycles were repeated in responding or stable patients. Data were analysed after a median of 30 months follow-up (range 16-48 months). In 42 patients, the immunologic response was studied and related to response and survival. The main toxicity were flu-like symptoms, malaise and transient liver enzyme elevations, necessitating IL-2 reduction to 2 mIU m(-2) in 29 patients, which should be considered the maximal tolerable dose. The response was 24% (eight out of 34, three complete response (CR), five partial response (PR)) in patients with metachronic metastases and 12% (three out of 25, 2CR, 1PR) in patients with synchronic metastases. Overall response was 19% (11 out of 59). Median survival was 9.5 months. All tested patients showed expansion and/or activation of lymphocytes, T cells and subsets, NK cells, eosinophils and monocytes. Pretreatment HLA-DR levels on monocytes and number of CD4(+)HLA-DR(+) cells correlated with response. Pretreatment number of CD4(+)HLA-DR(+) cells and postimmunotherapy levels of lymphocytes, CD3(+), CD4(+) and CD8(+) T cells, but not of NK or B cells, correlated with prolonged survival. Immunotherapy with concurrent subcutaneous GM-CSF, LD-IL-2 and IFNalpha has limited toxicity, can be given as outpatient treatment and can induce durable CR. Response and survival with this form of immunotherapy seem to be more dependent on expansion/activation of T cells than of NK cells.