High dose chemotherapy and hematopoietic stem cell transplantation: a study of treatment preference in patients with rheumatoid arthritis and rheumatologists

OBJECTIVE: Patients with intractable rheumatoid arthritis (RA) may benefit from treatment with high dose chemotherapy followed by rescue with autologous hematopoietic peripheral blood stem cell transplant (HSCT). We investigated whether the risks of this approach are acceptable to patients with RA and rheumatologists and whether risk taking by patients was associated with disease characteristics, socioeconomic variables, and/or personality traits. METHODS: A survey in the outpatient clinic was conducted among 2 cohorts of 45 (cohort A) and 51 (cohort B) RA patients with active disease. Patients received information about the potential benefit of HSCT (2/3 chance of a good clinical response, 1/3 no response) and treatment related morbidity and mortality. Cure was assumed not to be a realistic perspective. Cohort A was asked to choose between their own disease state for an indefinite time or HSCT. Nonparametric tests were performed to evaluate putative predictive factors that led patients to accept transplant related mortality (TRM): swollen joint count, tender joint count, visual analog scale (VAS) measures of disease activity and pain, erythrocyte sedimentation rate, Health Assessment Questionnaire (HAQ), socioeconomic variables, RA Quality of Life Questionnaire (RAQoL), and the Life Orientation Test. Cohort B was asked to consider a worst case scenario with respect to their disease activity. The minimal duration of benefit was assessed, given a TRM of 0.01% and 2%. To evaluate treatment preference of physicians, 96 Dutch rheumatologists responded to a hypothetical clinical case analogous to the interviews with RA patients. The minimum duration of benefit was assessed, given a TRM of 2% and the maximal TRM acceptable to rheumatologists if duration of benefit was 2 years in 2/3 patients. RESULTS: In cohort A, 5 of 45 patients were willing to accept risk of death. VAS disease activity (p = 0.006), VAS pain (p = 0.021), and HAQ (p = 0.05) were significantly higher in patients willing to accept risk of death. Religiosity (p = 0.093), a higher Ritchie Articular Index (p = 0.096), and low quality of life (by RAQoL) (p = 0.133) showed trends toward risk taking. In cohort B, 22 of 50 patients (44%) were willing to accept a risk of TRM related to HSCT. For the 22 patients the median required duration of benefit given a TRM of 2% was 5 years (range 1-15). Physicians also required a median duration of benefit of 5 years. CONCLUSION: We evaluated risk taking in patients with RA and physicians based on a realistic perspective in which the tradeoff between short term risks and possible longterm benefit of HSCT was investigated. Based on current efficacy data for HSCT (2 years improvement in 2/3 patients), half the patients would accept the current TRM of 2%, based on registry results. Patients willing to accept TRM had higher VAS disease activity, VAS pain, and HAQ. Doctors were more willing to accept mortality in the treatment of RA.     

Differences in fruit and vegetable intake and determinants of intakes between children of Dutch origin and non-Western ethnic minority children in the Netherlands – a cross sectional study

Background  

Fruit and vegetable consumption is low in the Netherlands and a key target in healthy diet promotion. However, hardly any information is available on differences in fruit and vegetable consumption between Dutch children and ethnic minority children. Therefore, the aim of present study was to determine differences in usual fruit and vegetable intake between native Dutch and non-Western ethnic minority children and to study differences in and mediating effects of potential psychosocial and environmental determinants.     

Are positive changes in potential determinants associated with increased fruit and vegetable intakes among primary schoolchildren? Results of two intervention studies in the Netherlands: The Schoolgruiten Project and the Pro Children Study

Background  

To investigate if positive changes or maintenance high scores on potential behavioral determinants of fruit and vegetable (F&V) intake are associated with increased or maintenance favorable levels of F&V intake frequency in the same time lapse or later in time. Data were used from two intervention studies in the Netherlands: the Schoolgruiten Project and the Pro Children Study.     

Iron deficiency in Indonesia: Current situation and intervention

Iron deficiency anaemia (IDA) has a large impact on productivity, mental performance, child growth, immunity and pregnancy outcome. In Indonesia, 50 to 70 million people (25–30% of the population) suffer from IDA. In 1995, the prevalence among pregnant women, underfives and female workers was 50.9%, 40.5% and 30%, respectively. Because nutrition and health are essential to human development, Indonesia has identified their improvement, including reducing IDA, a high priority. Several programs are implemented to control IDA. Iron supplementation for pregnant women started in 1974 and currently provides 60% with 90 tablets. Because infants and children cannot meet their iron requirements through diet alone, unless it contains fortified foods, distribution of iron-rich syrup to underfives was started in less developed villages in eastern Indonesia in 1996. Since 1996, factories should supplement their female workers with iron supplements once per week, 16 weeks per year, in order to increase their well-being and productivity. Other groups, such as female adolescents, school children and non-pregnant women are currently targeted through special projects and through IEC, using dietary guidelines, directed at a larger audience. With the increase in economic growth, self-purchasing of supplements and food fortification become more viable strategies. Producers of some brands of noodles and weaning foods are currently fortifying their products, while producers of “jamu” (traditional herb drinks) are increasing the content of enhancers of iron absorption. Reducing IDA in Indonesia is the goal of the Department of Health in collaboration with other departments, non-governmental organisations, international agencies, and the private sector.     

A new PCR-ELISA for diagnosis of visceral leishmaniasis in blood of HIV-negative subjects

The PCR-ELISA represents a promising advance for diagnosis of visceral leishmaniasis (VL) in blood samples. However, the method has been validated mostly with HIV-positive patients who are known to have high levels of parasitaemia. We developed a new PCR-ELISA assay for specific detection of Leishmania in patients' blood and validated it in Nepalese subjects with clinically suspected VL, almost all of whom were HIV-negative. For blood samples, PCR-ELISA was more sensitive (83.9%) than conventional PCR (73.2%), and demonstrated 100% and 87.2% specificity when using healthy controls who had never travelled to a VL-endemic area and controls from a VL-endemic area as references, respectively. We have demonstrated the ability of PCR-ELISA to detect parasites in blood of HIV-negative patients. The method could be used for epidemiological as well as clinical purposes, as it reduces the need for traumatic bone marrow sampling and risky spleen aspiration.     

The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo

Volatile anesthetics induce myocardial preconditioning and can also protect the heart when given at the onset of reperfusion-a practice recently termed "postconditioning." We investigated the role of mitochondrial KATP (mKATP)-channels in sevoflurane-induced cardioprotection for both preconditioning and postconditioning alone and whether there is a synergistic effect of both. Rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Infarct size was determined by triphenyltetrazolium staining. The following protocols were used: 1) preconditioning (S-Pre, n = 10, achieved by 2 periods of 5 min sevoflurane administration (1 MAC) followed by 10 min of washout); 2) sevoflurane postconditioning (1 MAC of sevoflurane given for 2 min at the beginning of reperfusion; S-Post, n = 10); 3) administration before and after ischemia (S-Pre + S-Post, n = 10). Protocols 1-3 were repeated in the presence of 5-hydroxydecanoate (5HD), a specific mKATP-channel-blocker (S-Pre + S-Post + 5HD, S-Pre + 5HD: n = 10; S-Post + 5HD: n = 9). Nine rats served as untreated controls (CON) or received 5HD alone (5HD, n = 10). Both S-Pre (23% +/- 13% of the area at risk, mean +/- sd) and S-Post (18% +/- 5%) reduced infarct size compared with CON (49% +/- 11%, both P < 0.05). S-Pre + S-Post resulted in a larger reduction of infarct size (12% +/- 5%, P = 0.054 versus S-Pre) compared with administration before or after ischemia alone. 5HD diminished the protection in all three sevoflurane treated groups (S-Pre + 5HD, 35% +/- 12%; S-Post + 5HD, 44% +/- 12%; S-Pre + S-Post + 5HD, 46% +/- 14%;) but given alone had no effect on infarct size (41% +/- 13%). Sevoflurane preconditioning and postconditioning protects against myocardial ischemia-reperfusion injury. The combination of preconditioning and postconditioning provides additive cardioprotection and is mediated, at least in part, by mKATP-channels.     

Photodynamic inactivation of fibroblasts by a cationic porphyrin

An important determinant of the clinical applicability and value of antimicrobial photodynamic inactivation (PDI) is the cytotoxicity of the treatment to human cells. We evaluated the in vitro cytotoxicity of PDI to human dermal fibroblasts using 5-phenyl-10,15,20-tris(N-methyl-4-pyridyl)porphyrin chloride (TriP[4]) as the photosensitiser. The fibroblasts were exposed to a PDI regime that is known to be sufficient for the inactivation of Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans [1]. The PDI experiments were carried out in phosphate-buffered saline (PBS) and in 6.25%, 12.5%, 25% and 50% fetal calf serum (FCS)/PBS suspensions. Cell viability subsequent to exposure was evaluated after 0 h, 6 h and 18 h using the methylthiazoletetrazolium (MTT) assay and compared to pretreatment values. At a TriP[4] concentration previously demonstrated to induce a 5log₁₀-unit reduction in a viable count for S. aureus, 79% of the fibroblasts were photo-inactivated. Increasing the FCS concentration in the medium protected the fibroblasts against PDI. Based on our in vitro results, we propose that in vivo PDI of S. aureus holds potential; however, PDI of P. aeruginosa and C. albicans will probably require such a strong PDI regime that it will induce substantial damage to fibroblasts.     

Food-for-work programs in Indonesia had a limited effect on anemia

Indonesia's economic crisis of late 1990s lowered consumption of micronutrient-rich foods, which increased the prevalence of micronutrient deficiencies, including anemia. As a postcrisis response, 5 nongovernmental organizations (NGOs) implemented Food for Work (FFW) programs to protect food consumption levels and nutritional status by providing rice, sometimes combined with oil and/or pinto beans. An independent evaluation assessed the effect of the FFW programs on nutrition outcomes, particularly anemia. A quasi-experimental design was used in which 1500 beneficiary and 1500 control households were randomly selected and followed in each of 3 urban and 2 rural sites. Baseline data were collected before program implementation and subsequently at approximately 6-mo intervals for 2.5 y. The poor were found to be appropriately targeted, and program participation ranged from 4 to 18 mo. The proportion of households with debts ranged from 32 to 70%; although it was higher among beneficiaries than controls, it increased among controls, but not beneficiaries. However, only among urban poor mothers in Surabaya were the odds of anemia at endline lower when participating in the FFW program (0.60, 95%CI [0.40-0.89]). Other risk factors for anemia in mothers and children included nutritional status (anemia at baseline, low BMI, receipt of vitamin A capsule, child age) and socioeconomic status (maternal education, having official residency in the area, income level). Thus, postcrisis FFW programs had limited effect on anemia, the main identified nutritional problem. Closer attention is required to the potential for affecting nutritional outcomes through FFW, including food aid quality and quantity and complementary nonfood interventions. Micronutrient deficiencies should be addressed directly via supplements and fortified foods.