[Collaborative care for co-morbid major depressive disorder in chronically ill outpatients in a general hospital]. / Collaborative care voor de behandeling van comorbide depressieve stoornis bij chronisch lichamelijk zieke patiënten op een polikliniek van een algemeen ziekenhuis.

BACKGROUND: Depression is highly prevalent in patients with chronic physical illnesses. A promising intervention for this group of patients is the collaborative care treatment as developed in the us. AIM: To demonstrate the prevalence of depression and the risk factors of depression in diabetes patients, to describe how the screening for depression can be carried out and to assess whether the collaborative care treatment in the Netherlands is effective. METHOD: A questionnaire was completed every three months in order to determine whether there was an improvement in patients' depression and physical symptoms. The outcomes were analysed by means of the multilevel logistic regression analyses. RESULTS: On the basis of the Patient Health Questionnaire, about 26% of the diabetes patients were found to have a depression. This questionnaire was validated for the measurement of depression in diabetes patients, the best results being found at a cut-off point of 12. In cases of fairly severe depression, collaborative care had no effect on depressive symptoms but did reduce severe physical complications. In cases of more severe depression, collaborative care only had an effect on depressive symptoms, but was not found to have any effect on physical complications. CONCLUSION: There is evidence that collaborative care can reduce depression and physical complications in chronically ill patients. However, more research is needed to find out whether collaborative care can become more effective if it is supplemented with digital methods and group therapy.

More co-morbid depression in patients with Type 2 diabetes with multiple complications. An observational study at a specialized outpatient clinic.

AIMS: The impact of depression on patients with chronic medical illnesses such as diabetes is well documented. Depression is relatively common in diabetes patients with diabetes-related complications and they are more likely to be referred to specialized outpatient facilities. Only a few studies have addressed the association between depression and multiple diabetes-related complications at these specialized outpatient facilities. The aim of this study was to determine the association between diabetes with multiple complications and depression in patients with Type 2 diabetes at a specialized outpatient clinic. METHODS: After giving informed consent, 1194 patients were screened for depression using the Patient Health Questionnaire (PHQ-9). Additional data on the type of diabetes and complications were taken from the medical records. Logistic regression analysis was conducted, with complications as the predictor variable and the probability of depression as the dependent variable. RESULTS: A total of 596 (63%) patients with Type 2 diabetes participated in the study. The presence of two or more complications (OR 2.23, 95% CI 1.02­2.94) was significantly associated with depression. Neuropathy (OR 1.7, 95% CI 1.10­2.77) and nephropathy (OR 1.68, 95% CI 1.00­2.48) were especially related to depression. CONCLUSIONS: Patients with Type 2 diabetes with two or more complications, especially neuropathy or nephropathy, are at high risk of depression. Knowing this can help clinicians identify patients at risk for depression and facilitate timely and adequate treatment.

Comparing methodologies for the cost estimation of hospital services.

The aim of the study was to determine whether the total cost estimate of a hospital service remains reliable when the cost components of bottom-up microcosting were replaced by the cost components of top-down microcosting or gross costing. Total cost estimates were determined in representative general hospitals in the Netherlands for appendectomy, normal delivery, stroke and acute myocardial infarction for 2005. It was concluded that restricting the use of bottom-up microcosting to those cost components that have a great impact on the total costs (i.e., labour and inpatient stay) would likely result in reliable cost estimates.

Randomized placebo-controlled trial of granulocyte-macrophage colony-stimulating factor in patients with chemotherapy-related febrile neutropenia.

PURPOSE: To determine whether granulocyte-macrophage colony-stimulating factor (GM-CSF) used in addition to standard inpatient antibiotic therapy shortens the period of hospitalization due to chemotherapy-induced neutropenic fever. PATIENTS AND METHODS: One hundred thirty-four patients with a hematologic (n = 47) or solid tumor (n = 87) who had severe neutropenia (< 0.5 x 10(9)/L) and fever (> 38.5 degrees C once or > 38 degrees C twice over a 12-hour observation period) were randomly assigned to receive GM-CSF 5 micrograms/kg/d (n = 65) or placebo (n = 69) in conjunction with broad-spectrum antibiotics for a minimum of 4 days and a maximum of 14 days. GM-CSF/placebo and antibiotics were stopped if the neutrophil count was greater than 1.0 x 10(9)/L and temperature less than 37.5 degrees C during 2 consecutive days, or for a leukocyte count > or = 10 x 10(9)/L, both followed by a 24-hour observation period (hospitalization period). RESULTS: Compared with placebo, GM-CSF enhanced neutrophil recovery. Median neutrophil counts at day 4 were 2.5 x 10(9)/L (range, 0 to 25) in the GM-CSF arm and 1.3 x 10(9)/L (range, 0 to 9) in the placebo arm (P < .001). No significant difference was observed with regard to median number of days with less than 1.0 x 10(9)/L neutrophils (4 v 4) or days of fever (3 v 3). The median number of days patients were hospitalized while on study was comparable in the GM-CSF and placebo groups at 6 (range, 3 to 14) versus 7 (range, 4 to 14), respectively, according to an intention-to-treat analysis (P = .27). Quality-of-life scores in 90 patients demonstrated significant differences in favor of the placebo group. Hospital costs were significantly higher for GM-CSF-treated patients if GM-CSF was included in the price (median costs, $4,140 [US] for GM-CSF v $590 for placebo; P < .05). CONCLUSION: These results indicate that GM-CSF does not affect the number of days for resolution of fever or the hospitalization period for this patient group, although a significant effect of GM-CSF was observed on neutrophil recovery.

Sleep duration differences between children of migrant and native origins.

AIM: To explore whether primary school children of migrant and native Dutch origins differ regarding their sleep duration per night, a risk for overweight and obesity, and to determine to what degree differences in parenting styles contribute to these differences. SUBJECTS AND METHODS: A cross-sectional survey, including 1,943 children aged 8-9 years old and their primary caregivers, was performed. Data were collected from primary schools in cities and adjacent municipalities in The Netherlands: Eindhoven and Rotterdam. The outcome measure was mean sleep duration per night. The main independent variable was migrant background, based on the country of birth of the parents. A possible mediating variable was parenting style (rejecting, neglecting, permissive, authoritarian, authoritative). Age and sex of the child as well as parental socioeconomic status, as indicated by educational level, were added as confounders. RESULTS: Dutch children have the highest sleep duration: more than 11 h (mean = 670.1; SD = 27.7). All migrant children show less than 11 h of sleep per night. Migrant children of non-Western origin, especially Turkish and Moroccan children, show the lowest sleep duration per night. Parenting styles do not contribute to these differences. CONCLUSION: Migrant background is associated with sleep duration. As children of migrant origin are, in general, at higher risk for overweight and obesity and sleep duration is regarded as a risk factor for overweight and obesity, further investigation of this association is needed.

An economic model to assess the savings from a clinical application of haematopoietic growth factors.

Patients receiving chemotherapy frequently develop fever and neutropenia. Haematopoietic growth factors (HGFs) may decrease the duration of such episodes or may prevent a febrile neutropenic episode. In this study we introduce a Markov type economic model for the hospital which calculates all relevant direct costs and savings of HGF therapy and may support decisions on HGF administration. A distinction is made between patients receiving intensive and standard chemotherapy schedules. Our results indicate that HGFs can induce savings in intensive chemotherapy and standard chemotherapy following neutropenic fever. Prophylactic administration of HGF is cost-effective if the risk of infection is considerable. The risk of infection depends on underlying malignancy, corresponding treatment modalities and the health condition of the patient. The model is meant as an analytical framework and should be used carefully, as not all benefits (e.g. benefits to the patients) are considered. These benefits may be balanced against the additional costs or savings resulting from the economic model.

Measurement and valuation of quality of life in economic appraisal of cancer treatment.

In the economic evaluation (EE) of technologies in cancer treatment at least three endpoints are relevant: costs, survival and quality of life (QoL). This article is focused on QoL. EE requires the use of generic and valuation QoL instruments at a disease non-specific level, but the inclusion of cancer-specific instruments may be advisable, particularly for reasons of explanation if changes in dimensions are small or conflicting. Given the pros and cons of the available questionnaires, we advocate the use of the Nottingham Health Profile, the EuroQol and the Rotterdam Symptom Checklist. In our experience the QoL issue in EE linked with cancer trials is associated with practical problems like questionnaire composition, follow-up time, interviewing schedule, patients' compliance and doctors' acceptance. These problems are discussed and some practical guidelines for the design of QoL measurement in cancer trials are given.

Economic evaluation alongside cancer trials: methodological and practical aspects.

A recent extension of clinical evaluation is "economic evaluation", which seeks to characterise each relevant alternative health care strategy in terms of a summary measure incorporating the costs and benefits of such strategies. In an economic evaluation, separate measurements of resource volumina and resource prices on the cost side, and separate measurements of survival and quality of life effects and valuation of these outcome effects on the benefit side are required. From these effect parameters, which should be calculated for all competing strategies considered in the analysis, the relative cost-effectiveness of one strategy as against the other can be derived. The degree of generalisability of the study results determines the validity of economic evaluation in decision-making. This depends on the generalisability of the clinical findings, and in this respect the so-called "piggyback" economic evaluation, which is added to a clinical trial, has its limitations. In the field of cancer, specific attention should be given to costs and effects occurring after non-mortality endpoints, to patient and family costs and to variations in treatments between settings of care. It is argued that conventional clinical trials and economic evaluations will integrate further in the future.

Peripheral blood progenitor cell transplantation mobilised by r-metHuG-CSF (filgrastim); a less costly alternative to autologous bone marrow transplantation.

In a retrospective study, we calculated the treatment costs of 63 patients who received either autologous bone marrow transplantation (ABMT) with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) (filgrastim) (n = 13) or without r-metHuG-CSF (n = 22) or alternatively, peripheral blood progenitor cell (PBPC) transplantation mobilised by r-metHuG-CSF (n = 28). The recovery of granulocytes, platelets and reticulocytes after PBPC was markedly accelerated as compared with ABMT with or without r-metHuG-CSF. The accelerated haematopoietic recovery was associated with a reduction in platelets and red blood cell transfusion requirements, with a reduction in episodes of fever and with earlier discharge from the hospital. This resulted in the average cost per treatment of the PBPC group being almost 30% lower than the treatment costs in the ABMT groups.

The costs of peripheral blood progenitor cell reinfusion mobilised by granulocyte colony-stimulating factor following high dose melphalan as compared with conventional therapy in multiple myeloma.

In a retrospective study, we calculated the treatment costs of 26 patients, who received either high dose melphalan combined with granulocyte colony-stimulating factor (G-CSF; filgrastim)(n = 7) or without G-CSF (n = 11) or alternatively, peripheral blood progenitor cell reinfusion (PBPC) mobilised by G-CSF following high dose melphalan. In comparison with the control group, a shortening of the pancytopenic period and platelet recovery was noticed in the PBPC group. This resulted in a reduction in hospital costs, diagnostics, laboratory services, total parenteral nutrition and transfusions. The average costs per treatment in the PBPC group amounted to about US$ 17,908 as compared to US$ 32,223 in the control group, implying a cost reduction of 44% when changing to PBPC reinfusion.

Cost effectiveness of cholesterol-lowering therapy in The Netherlands. Simvastatin versus cholestyramine.

Using a model of coronary heart disease incidence based on multivariate logistic regression functions from the Framingham Heart Study, the cost effectiveness of simvastatin was compared with that of cholestyramine in preventing such disease. For men with initial cholesterol levels of 310 mg/dl, the cost effectiveness of cholestyramine, expressed in Dutch guilders, ranges from approximately 220,000 to 510,000 guilders per year of life saved, depending on age at initiation of therapy. For simvastatin, cost-effectiveness ratios range from 50,000 to 110,000 guilders per year of life saved among this group of men. Results are similar for women, although the cost effectiveness of both agents is considerably less. These results suggest that simvastatin is substantially more cost effective than cholestyramine; that it compares well with other generally accepted medical practices, especially if therapy is initiated at an early age; and that simvastatin should become accepted as a drug of first choice in the treatment of persons with elevated serum cholesterol levels as its long-term safety record becomes more established.

The cost-effectiveness of preservation with UW and EC solution for use in cadaveric kidney transplantation in the case of single kidney donors.

University of Wisconsin (UW) solution is now commonly used as a single-flush solution during multiorgan procurement for effective preservation of all intraabdominal organs including the kidney. Many kidneys from single kidney donors are still preserved in Eurocollins solution and the question is whether preservation in UW solution is more cost-effective. A European randomized multicenter trial was organized by the Department of Surgery of Leiden University in close cooperation with Eurotransplant to study the efficacy of UW solution as compared with EC solution. On the basis of this trial we found that at three months after transplant 92.4% of the patients in the UW group had a functioning graft in comparison with 88.4% in the EC group (similar figures after one year were 88.2% and 82.5%, P approximately 0.04), while health care expenditure during these first three months was on average US$ 700 lower for the UW group than for the EC group, taking into account the price difference in the preservation fluids. The long-term benefits of using UW solution as compared with EC solution were conservatively estimated at US$ 7000 per patient reflecting the additional expenses for dialysis in the EC group. We concluded that the extra costs of using UW solution instead of EC solution (US$ 230 per kidney) can be easily earned back within three months and that the long-term savings of such a strategy are considerable. Moreover, the health status of patients in the UW group is expected to be better on the average than in the EC group. Simply reacting to the price tag of the UW solution may be penny-wise but pound-foolish.

The role of a decision rule in symptomatic pulmonary embolism patients with a non-high probability ventilation-perfusion scan.

BACKGROUND: In order to improve the use of information contained in the medical history and physical examination in patients with suspected pulmonary embolism and a non-high probability ventilation-perfusion scan, we assessed whether a simple, quantitative decision rule could be derived for the diagnosis or exclusion of pulmonary embolism. METHODS: In 140 consecutive symptomatic patients with a non-high probability ventilation-perfusion scan and an interpretable pulmonary angiogram, various clinical and lung scan items were collected prospectively and analyzed by multivariate stepwise logistic regression analysis to identify the most informative combination of items. RESULTS: The prevalence of proven pulmonary embolism in the patient population was 27.1%. A decision rule containing the presence of wheezing, previous deep venous thrombosis, recently developed or worsened cough, body temperature above 37 degrees C and multiple defects on the perfusion scan was constructed. For the rule the area under the Receiver Operating Characteristic curve was larger than that of the prior probability of pulmonary embolism as assessed by the physician at presentation (0.76 versus 0.59; p = 0.0097). At the cut-off point with the maximal positive predictive value 2% of the patients scored positive, at the cut-off point with the maximal negative predictive value pulmonary embolism could be excluded in 16% of the patients. CONCLUSIONS: We derived a simple decision rule containing 5 easily interpretable variables for the patient population specified. The optimal use of the rule appears to be in the exclusion of pulmonary embolism. Prospective validation of this rule is indicated to confirm its clinical utility.

Clinical benefits and cost-effectiveness of lowering serum cholesterol levels: the case of simvastatin and cholestyramine in The Netherlands.

To assess the cost-effectiveness of cholesterol-reducing therapy with cholestyramine and simvastatin in the primary prevention of coronary artery disease in The Netherlands, a model of coronary artery disease incidence was used based on multivariate logistic risk functions from the Framingham study. For men with initial cholesterol levels of 8 mmol/liter, the cost per year of life saved of cholestyramine, expressed in Dutch guilders (NLG; 1 NLG = $0.50), ranges from approximately NLG 208,000 to NLG 483,000, depending on the patient's age at initiation of therapy. For simvastatin, cost-effectiveness ranges from NLG 46,000 to NLG 98,000 per year of life saved among this group of men. Similar differences between simvastatin and cholestyramine therapy prevail among women, although the costs per year of life saved for both agents are considerably higher. These results suggest that (1) simvastatin is substantially more cost effective than is cholestyramine; (2) simvastatin therapy compares favorably with other generally accepted medical practices, especially if treatment is initiated at an early age; and (3) as its long-term safety record becomes more established, simvastatin may become accepted as a drug of first choice in the treatment of persons with elevated serum cholesterol levels.

Cost-effectiveness of ABMT in comparison with CHOP chemotherapy in patients with intermediate- and high-grade malignant non-Hodgkin's lymphoma (NHL).

A prospective randomized clinical trial with simultaneous data collection for an economic appraisal was carried out to assess the effectiveness, quality of life and cost implications of ABMT vs standard chemotherapy in slowly responding patients with intermediate- and high-grade malignant non-Hodgkin's lymphoma (NHL). The patients had a partial response after three cycles of chemotherapy and had no evidence of BM involvement of NHL. The overall and disease-free survival at 3 years were 61% and 60%, respectively, in the ABMT group and 85% and 77% in the CHOP group (P = NS). Moreover, there were more (severe) complications and symptoms in the ABMT than in the CHOP group. The average costs of CHOP chemotherapy were significantly lower than the average costs in the ABMT group (CHOP: US$ 3118 vs ABMT: US$ 34,447). Considering long-term consequences the ABMT group was more expensive (US$ 34,580) and patients experienced 0.14 life years and 0.22 quality adjusted life years less than the CHOP group (discount rate 5%). As a result, changing therapy from CHOP to ABMT, as primary treatment in slow responders to CHOP, can not be recommended as the required additional investment does not produce health gains in terms of survival or quality of life.

Costs of introducing autologous BMT in the treatment of lymphoma and acute leukaemia in The Netherlands.

In a retrospective study we calculated the costs of introducing autologous BMT in the treatment of patients with malignant lymphoma and acute leukaemia in The Netherlands. The cost analysis has been performed in five university hospitals and one cancer centre, in a series of patients with intermediate and high grade non-Hodgkin's lymphoma (NHL) and patients with AML. Conventional treatment consisted of chemotherapy. The average costs of the conventional NHL treatment varied from US$3120 to U$12,900. The costs of autologous BMT amounted to US$40,220. In the AML group the costs of conventional treatment amounted to about US$11,040, as only 50% of the patients were treated further. The costs of autologous BMT including a follow-up period of 2 years, amounted to US$55,440. In The Netherlands the total number of autologous BMTs per year in these patient groups was estimated at 230; 180 in the NHL group and 50 in the AML group. The costs of introducing autologous BMT to the NHL group will vary between 4.93 and 6.68 million dollars and for the AML group these costs were estimated at 2.22 million dollars. As a result, the total extra costs of introducing autologous BMTs are expected to be between 7.15 and 8.9 million dollars.

The friction cost method for measuring indirect costs of disease.

A new approach for estimating the indirect costs of disease, which explicitly considers economic circumstances that limit production losses due to disease, is presented (the friction cost method). For the Netherlands the short-term friction costs in 1990 amount to 1.5-2.5% of net national income (NNI), depending on the extent to which short-term absence from work induces production loss and costs. The medium-term macro-economic consequences of absence from work and disability reduce NNI by an additional 0.8%. These estimates are considerably lower than estimates based on the traditional human capital approach, but they better reflect the economic impact of illness.

Referrals and demand for specialist care in the Netherlands.

Three independent sets of data are analyzed to investigate the determinants of referrals from general practitioners to specialists, the demand for specialist care, and the rapid increase in referrals and use of specialists in the Netherlands. Individual determinants of demand are examined with data from a three-man group practice; macroanalyses are conducted on cross-section data from all service areas of the Dutch Sickness Fund Organization for 1971 and 1973 and cross-section time-series data from all provinces for the period from 1960 to 1972. Regression coefficients are estimated for the number of referrals to specialists and the amount of care given by specialists, with respect to explanatory variables that induce both socioeconomic and care-supply factors. Results are discussed in light of M. Feldstein's classification of three types of care, in which for some types the physician is seen as generating the demand for care. The authors conclude that demand for specialist outpatient care is in large part supply-determined and that general practitioners substitute for specialists; they also suggest that the dual physician-payment system in the Netherlands (capitation for legally insured patients and fee-for-service for privately insured patients) contributes to increased use of specialist care.

Determinants of hospital utilization in the Netherlands.

Hospital use in the Netherlands is examined in a cross-section analysis of 1969 and 1971 data for 120 service regions. Elasticities of admissions with respect to bed supply and supply of general practitioners are calculated, and the substitutability of first level care (by general practitioners) for hospital care is considered. Substitution effects found indicate that the Dutch government's plan to reduce the ratio of hospital beds to population is feasible.

A practical guide for calculating indirect costs of disease.

There may be some discussion about whether indirect costs should be taken into account at all in an economic appraisal, but there is certainly considerable debate about the proper way of estimating these costs. This reviews offers a practical guide for quantifying and valuing these indirect costs of disease, both at an aggregated level of general cost of illness studies, and in an economic appraisal of specific healthcare programmes. Two methods of calculating these costs are considered: the traditional human capital approach, and the more recently developed friction cost method. The former method estimates the potential value of lost production as a result of disease, whereas the latter method intends to derive more realistic estimates of indirect costs, taking into account the degree of scarcity of labour in the economy. All necessary steps in the estimation procedure and the data required at various points will be described and discussed in detail.